* 0 - Asymptomatic (Fully active, able to carry on all predisease activities without restriction)
* 1 - Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. For example, light housework, office work)
* 2 - Symptomatic, <50% in bed during the day (Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours)
* 3 - Symptomatic, >50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours)
* 4 - Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair)
* 5 - Death
Sunday, August 23, 2009
AUC and carboplatin dosing
Carboplatin dose (mg) = AUC x (CrCl in ml/min + 25)
CrCl (male) = ([140-age] x weight in kg)/(serum creatinine x 72)
CrCl (female) = CrCl (male) x 0.85
CrCl (male) = ([140-age] x weight in kg)/(serum creatinine x 72)
CrCl (female) = CrCl (male) x 0.85
Colon cancer
1. Synchronous
a. Colonoscopy
b. Chest/abdominal/pelvic CT
c. FBC, PLT, chemistry profile
d. CEA
e. KRAS
f. needle biopsy, if clinically indicated
g. PET scan only if potentially surgically curable M1 disease
2. Adjuvant
a. 5FU/leucovorin
- leucovorin 500mg/m2 given as 2h infusion and repeated weekly x 6; 5FU 500mg/m2 given bolus 1h after start of leucovorin and repeted 6 x weekly. Every 8 weeks for 4 cycles
- 5FU 370-400mg/m2 + leucovorin 200mg/m2 daily x 5d, every 28d x 6 cycles
b. Capecitabine 1250mg/m2 bd D1-14 every 3 weeks x 24 wks
c. FLOX
- 5FU 500mg/m2 IV bolus weekly x 6 + leucovorin 500mg/m2 IV weekly x 6, each 8 week cycle x 3 with oxaliplatin 85mg/m2 IV administered on weeks 1,3 and 5 of each 8 week cycle x 3
d. FOLFOX 4
oxaliplatin 85mg/m2 IV over 2h D1
leucovorin 400mg/m2 IV over 2h D1
5FU 400mg/m2 IV bolus on D1 then 1200mg/m2/day x 2 days (total 2400mg/,2 over 46-48 hr) continuous infusion
Repeat every 2 weeks
3. Advanced or metastatic disease
a. FOLFOX 4
Oxaliplatin 85mg.m2 IV over 2 hours D1
Leucovorin 200mg/m2 IV over 2 hours D1 & 2
Followed on D 1 & 2 by 5FU 400mg/m2 IV bolus then 600mg/m2 IV over 22 hours continuous infusion
Repeat every 2 weeks
b. mFOLFOX 6
Oxaliplatin 85mg/m2 IV over 2 hours D1
Leucovorin 400mg/m2 IV over 2 hours D1
5FU 400mg/m2 IV bolus on D1 then 1200mg/m2/day x 2 days (total 2400mg/m2 over 46-48h) continuous infusion
Repeat every 2 weeks
c. CapeOX
Oxaliplatin 130mg/m2 D1
Capecitabine 850-1000mg/m2 bd for 14 days
Repeat every 3 weeks
d. FOLFIRI
(i)
Irinotecan 180mg/m2 IV over 30-120 minutes D1
Leucovorin 200mg/m2 IV infusion to match duration of irinotecan infusion, D1 & 2
Followed on D1 & 2 by 5FU 400mg/m2 IV bolus then 600mg/m2 IV over 22 hours continuous infusion
Repeat every 2 weeks
(ii)
Irinotecan 180mg/m2 IV over 30-120 min D1
Leucovorin 400mg/m2 IV infusion to match duration of irinotecan infusion D1
5FU 400mg/m2 IV bolus D1 then 1200mg/m2/day x 2 days (total 2400mg/m2 over 46-48h) continuous infusion
Repeat every 2 weeks
e. Bevacizumab + 5FU containing regimens
Bevacizumab5mg/kg IV every 2 weeks + 5FU and leucovorin/FOLFOX/FOLFIRI
Bevacizumab 7.5mg/kg IV every 3 weeks + CapeOX
f. Capecitabine 2000-2500mg/m2/day PO in 2 divided doses, D1-14 flw by 7 days rest/ Repeat every 3 weeks
g. Bolus or infusional 5FU/leucovorin
i. Roswell-Park regimen
Leucovorin 500mg/m2 IV over 2 hours D1/8/15/22/29/36
5FU 50mg/m2 IV bolus 1 hour after start of leucovorin, D1/8/15/22/29/36
Repeat every 8 weeks
ii. Biweekly
Leucovorin 200mg/m2 IV over 2 hours D1 & 2
5FU 400mg/m2 IV bolus then 600mg/m2 IV over 22 hours continuous infusion D1 & 2
Repeat every 2 weeks
iii. Simplified biweekly infusional 5FU/LV (sLV5FU2)
Leucovorin 400mg/m2 IV over 2 hours on D1 followed by 5FU bolus 400mg/m2 and then 1200mg/m2/day x 2 days (total 2400mg/m2 over 46/48 h) continuous infusion
Repeat every 2 weeks
iv. Weekly
Leucovorin 20mg/m2 as 2 h infusion
5FU 500mg/m2 bolus administered 1h after LV infusion
Repeat every week
5FU 2600mg/m2 by 24h infusion plus leucovorin 500mg/m2
Repeat every week
h. FOLFOXIRI
Irinotecan 165mg/m2 IV D1, oxaliplatin 85mg/m2 D1
Leucovorin 400mg/m2 D1, fluorouracil 3200mg/m2 over 48h
Continuous infusion starting on D1
Repeat every 2 weeks
i. Irinotecan 300-350mg/m2 IV over 30-90 minutes D1 repeat every 3 wks
j. Cetuximab (KRAS wild type gene only) +/- irinotecan
Cetuximb 400mg/m2 1st infusion then 250mg/m2 IV weekly
Or
Cetuximab 500mg/m2 IV every 2 weeks
+/-
Irinotecan 300-350mg/m2 IV every 3 weeks
Or
Irinotecan 180mg/m2 IV every 2 weeks
Or
Irinotecan 125mg/m2 every week for 4 weeks
Every 6 weeks
k. Cetuximab (KRAS wild type gene only)
Cetuximab 400mg/m2 1st infusion then 250mg/m2 IV weekly
l. Panitumumab (KRAS wild type gene only)
Panitumumab 6mg/kg IV over 60 minutes every week
4. Surveillance
a. history and physical every 3-6 mo for 2y, then every 6 mo for total of 5y
b. CEA every 3-6 mo for 2y, then every 6 mo for a total of 5y for T2 or greater lesions
c. Chest/abdominal/pelvic CT annually x 3y for patients at high risk for recurrence
d. Colonoscopy in 1y except if no preoperative colonoscopy due to obstructing esion, colonoscopy in 3-6 mo: if advanced adenoma repeat in 1y then if no advanced adenoma repeat in 3y then every 5y
e. PET (serial CEA elevation)
f. Breast exam q1-3y btw ages 20-40, annual mammogram >40 yo, high risk = breast MRI and mammogram annually
g. Cervical CA, prostate CA screening
a. Colonoscopy
b. Chest/abdominal/pelvic CT
c. FBC, PLT, chemistry profile
d. CEA
e. KRAS
f. needle biopsy, if clinically indicated
g. PET scan only if potentially surgically curable M1 disease
2. Adjuvant
a. 5FU/leucovorin
- leucovorin 500mg/m2 given as 2h infusion and repeated weekly x 6; 5FU 500mg/m2 given bolus 1h after start of leucovorin and repeted 6 x weekly. Every 8 weeks for 4 cycles
- 5FU 370-400mg/m2 + leucovorin 200mg/m2 daily x 5d, every 28d x 6 cycles
b. Capecitabine 1250mg/m2 bd D1-14 every 3 weeks x 24 wks
c. FLOX
- 5FU 500mg/m2 IV bolus weekly x 6 + leucovorin 500mg/m2 IV weekly x 6, each 8 week cycle x 3 with oxaliplatin 85mg/m2 IV administered on weeks 1,3 and 5 of each 8 week cycle x 3
d. FOLFOX 4
oxaliplatin 85mg/m2 IV over 2h D1
leucovorin 400mg/m2 IV over 2h D1
5FU 400mg/m2 IV bolus on D1 then 1200mg/m2/day x 2 days (total 2400mg/,2 over 46-48 hr) continuous infusion
Repeat every 2 weeks
3. Advanced or metastatic disease
a. FOLFOX 4
Oxaliplatin 85mg.m2 IV over 2 hours D1
Leucovorin 200mg/m2 IV over 2 hours D1 & 2
Followed on D 1 & 2 by 5FU 400mg/m2 IV bolus then 600mg/m2 IV over 22 hours continuous infusion
Repeat every 2 weeks
b. mFOLFOX 6
Oxaliplatin 85mg/m2 IV over 2 hours D1
Leucovorin 400mg/m2 IV over 2 hours D1
5FU 400mg/m2 IV bolus on D1 then 1200mg/m2/day x 2 days (total 2400mg/m2 over 46-48h) continuous infusion
Repeat every 2 weeks
c. CapeOX
Oxaliplatin 130mg/m2 D1
Capecitabine 850-1000mg/m2 bd for 14 days
Repeat every 3 weeks
d. FOLFIRI
(i)
Irinotecan 180mg/m2 IV over 30-120 minutes D1
Leucovorin 200mg/m2 IV infusion to match duration of irinotecan infusion, D1 & 2
Followed on D1 & 2 by 5FU 400mg/m2 IV bolus then 600mg/m2 IV over 22 hours continuous infusion
Repeat every 2 weeks
(ii)
Irinotecan 180mg/m2 IV over 30-120 min D1
Leucovorin 400mg/m2 IV infusion to match duration of irinotecan infusion D1
5FU 400mg/m2 IV bolus D1 then 1200mg/m2/day x 2 days (total 2400mg/m2 over 46-48h) continuous infusion
Repeat every 2 weeks
e. Bevacizumab + 5FU containing regimens
Bevacizumab5mg/kg IV every 2 weeks + 5FU and leucovorin/FOLFOX/FOLFIRI
Bevacizumab 7.5mg/kg IV every 3 weeks + CapeOX
f. Capecitabine 2000-2500mg/m2/day PO in 2 divided doses, D1-14 flw by 7 days rest/ Repeat every 3 weeks
g. Bolus or infusional 5FU/leucovorin
i. Roswell-Park regimen
Leucovorin 500mg/m2 IV over 2 hours D1/8/15/22/29/36
5FU 50mg/m2 IV bolus 1 hour after start of leucovorin, D1/8/15/22/29/36
Repeat every 8 weeks
ii. Biweekly
Leucovorin 200mg/m2 IV over 2 hours D1 & 2
5FU 400mg/m2 IV bolus then 600mg/m2 IV over 22 hours continuous infusion D1 & 2
Repeat every 2 weeks
iii. Simplified biweekly infusional 5FU/LV (sLV5FU2)
Leucovorin 400mg/m2 IV over 2 hours on D1 followed by 5FU bolus 400mg/m2 and then 1200mg/m2/day x 2 days (total 2400mg/m2 over 46/48 h) continuous infusion
Repeat every 2 weeks
iv. Weekly
Leucovorin 20mg/m2 as 2 h infusion
5FU 500mg/m2 bolus administered 1h after LV infusion
Repeat every week
5FU 2600mg/m2 by 24h infusion plus leucovorin 500mg/m2
Repeat every week
h. FOLFOXIRI
Irinotecan 165mg/m2 IV D1, oxaliplatin 85mg/m2 D1
Leucovorin 400mg/m2 D1, fluorouracil 3200mg/m2 over 48h
Continuous infusion starting on D1
Repeat every 2 weeks
i. Irinotecan 300-350mg/m2 IV over 30-90 minutes D1 repeat every 3 wks
j. Cetuximab (KRAS wild type gene only) +/- irinotecan
Cetuximb 400mg/m2 1st infusion then 250mg/m2 IV weekly
Or
Cetuximab 500mg/m2 IV every 2 weeks
+/-
Irinotecan 300-350mg/m2 IV every 3 weeks
Or
Irinotecan 180mg/m2 IV every 2 weeks
Or
Irinotecan 125mg/m2 every week for 4 weeks
Every 6 weeks
k. Cetuximab (KRAS wild type gene only)
Cetuximab 400mg/m2 1st infusion then 250mg/m2 IV weekly
l. Panitumumab (KRAS wild type gene only)
Panitumumab 6mg/kg IV over 60 minutes every week
4. Surveillance
a. history and physical every 3-6 mo for 2y, then every 6 mo for total of 5y
b. CEA every 3-6 mo for 2y, then every 6 mo for a total of 5y for T2 or greater lesions
c. Chest/abdominal/pelvic CT annually x 3y for patients at high risk for recurrence
d. Colonoscopy in 1y except if no preoperative colonoscopy due to obstructing esion, colonoscopy in 3-6 mo: if advanced adenoma repeat in 1y then if no advanced adenoma repeat in 3y then every 5y
e. PET (serial CEA elevation)
f. Breast exam q1-3y btw ages 20-40, annual mammogram >40 yo, high risk = breast MRI and mammogram annually
g. Cervical CA, prostate CA screening
Breast cancer: metastatic disease
8. Metastatic disease
a. Preferred single agents
i. Anthracyclines:
- doxorubicin 60-75mg/m2 IV D1 cycled every 21 days or 20mg/m2 IV weekly
- epirubicin 60-90 mg/m2 IV D1 cycled every 21 days
- pegylated liposomal doxorubicin 50mg/m2 IV D1 cycled every 28 days
ii. Taxanes
- paclitaxel 175mg/m2 IV D1 cycled every 21 days or 80mg/m2 IV weekly
- docetaxel 60-100mg/m2 IV D1 cycled every 21 days or 40mg/m2 IV weekly for 6 wks followed by a 2 week rest then repeat
- albumin-bound paclitaxel 100mg/m2 or 150mg/m2 D1, 8 and 15 IV cycled every 28 days or 260mg/m2 IV cycled every 21 days
iii. Anti-metabolites
- capecitabine 1000-1250 mg/m2 PO bd D1-14 cycled every 21 days
- gemcitabine 800-11200mg/m2 IV D1, 8 and 15
iv. Other microtubule inhibitors
- vinorelbine 25mg/m2 IV weekly
b.Other single agents
- cyclophosphamide
- mitoxantrone
- cisplatin
- etoposide po
- vinblastine
- fluorouracil Cl
- ixabepilone
c. Preferred agents with Bevacizumab
- paclitaxel 90mg/m2 by 1h IV D1, 8 & 15
- bevacizumab 10mg/kg IV D1 & 15
- cycled every 28 days
d. Preferred chemotherapy combinations
- CAF
Cyclophasphamide 100mg/m2 PO D1-14
Doxorubicin 30mg/m2 IV D1 & 8
5FU 500mg/m2 IV D1 & 8
Cycled every 28 days
- FAC
5FU 500m/m2 IV D1 & 8 or D1 & 4
Doxorubicin 50mg/m2 IV D1
Cyclophosphamide 500mg/m2 IV D1
Cycled every 21 days
- FEC
Cyclophasmide 400mg/m2 IV D1 & 8
Epirubicin 50mg/m2 IV D1 & 8
5FU 500mg/m2 IV D1 & 8
Cycled every 28 days
- AC
Doxorubicin 60mg/m2 IV D1
Cyclophasphamide 600mg/m2 IV D1
Cycled every 21 days
- EC
Epirubicin 75mg/m2 IV D1
Cyclophosphamide 600mg/m2 IV D1
Cycled every 21 days
- AT
Doxorubicin 60mg/m2 IV D1 or 50mg/m2 IV D1
Paclitaxel 125-200 mg/m2 IV D1 or Docetaxel 75mg/m2 IV D1
Cycled every 21 days
- CMF
Cyclophosphamide 100mg/m2 PO D1-14
Methotrexate 40mg/m2 IV D1 & 8
5FU 600mg/m2 Iv D1 & *
Cycled every 28 days
- docetaxel/capecitabine
Docetaxel 75mg/m2 IV D1
Capecitabine 950mg/m2 PO bd 1-14
Cycled every 21 days
- GT
Paclitaxel 175mg/m2 IV D1
Gemcitabine 1250 mg/m2 IV D1 & 8 (following paclitaxel on D1)
Cycled every 21 days
e. Other combinations
- ixabepilone + capecitabine
Ixabepilone 40mg/m2 IV D1
Capecitabine 2000mg/m2 PO D1-14
Cycled every 21 days
f. Preferred first line agents for Her-2 positive disease: Trastuzumab 4 mg/kg IV D1 followed by 2mg/kg IV weekly or 8mg/kg IV D1 followed by 6mg/kg IV every 3 wks with:
- paclitaxel + carboplatin (PCH)
Carboplatin AUC of 6 IV D1
Paclitaxel 175mg/m2 IV D1
Cycled every 21 days
- weekly TCH chemotherapy
Paclitaxel 80mg/m2 IV D1, 8 & 15
Carboplatin AUC of 2 IV D1, 8 & 15
Cycled every 28 days
- paclitaxel 175mg/m2 IV D1 cycled every 21 days or 80-90mg/m2 IV weekly
- docetaxel 80-100mg/m2 IV D1 cycled every 21 days or 35mg/m2 IV infusion weekly
- vinorelbine 25mg/m2 IV weekly
- capecitabine 1000-1250mg/m2 PO bd D1-14 cycled every 21 days
g. Preferred agents for trastuzumab-exposed Her2-positive disease
- lapitinib 1250mg PO daily D1-21 + capecitabine 1000mg/m2 PO bd D1-14 cycled every 21 days
- trastuzumab + other first line agents
- trastuzumab + capecitabine
- trastuzumab + lapatinib (without cytotoxic therapy) 1000mg PO daily
(trastuzumab 4mg/kg IV D1 followed by 2mg/kg IV weekly or 8mg/kg IV D1 followed by 6mg/kg Iv every 3 wks)
a. Preferred single agents
i. Anthracyclines:
- doxorubicin 60-75mg/m2 IV D1 cycled every 21 days or 20mg/m2 IV weekly
- epirubicin 60-90 mg/m2 IV D1 cycled every 21 days
- pegylated liposomal doxorubicin 50mg/m2 IV D1 cycled every 28 days
ii. Taxanes
- paclitaxel 175mg/m2 IV D1 cycled every 21 days or 80mg/m2 IV weekly
- docetaxel 60-100mg/m2 IV D1 cycled every 21 days or 40mg/m2 IV weekly for 6 wks followed by a 2 week rest then repeat
- albumin-bound paclitaxel 100mg/m2 or 150mg/m2 D1, 8 and 15 IV cycled every 28 days or 260mg/m2 IV cycled every 21 days
iii. Anti-metabolites
- capecitabine 1000-1250 mg/m2 PO bd D1-14 cycled every 21 days
- gemcitabine 800-11200mg/m2 IV D1, 8 and 15
iv. Other microtubule inhibitors
- vinorelbine 25mg/m2 IV weekly
b.Other single agents
- cyclophosphamide
- mitoxantrone
- cisplatin
- etoposide po
- vinblastine
- fluorouracil Cl
- ixabepilone
c. Preferred agents with Bevacizumab
- paclitaxel 90mg/m2 by 1h IV D1, 8 & 15
- bevacizumab 10mg/kg IV D1 & 15
- cycled every 28 days
d. Preferred chemotherapy combinations
- CAF
Cyclophasphamide 100mg/m2 PO D1-14
Doxorubicin 30mg/m2 IV D1 & 8
5FU 500mg/m2 IV D1 & 8
Cycled every 28 days
- FAC
5FU 500m/m2 IV D1 & 8 or D1 & 4
Doxorubicin 50mg/m2 IV D1
Cyclophosphamide 500mg/m2 IV D1
Cycled every 21 days
- FEC
Cyclophasmide 400mg/m2 IV D1 & 8
Epirubicin 50mg/m2 IV D1 & 8
5FU 500mg/m2 IV D1 & 8
Cycled every 28 days
- AC
Doxorubicin 60mg/m2 IV D1
Cyclophasphamide 600mg/m2 IV D1
Cycled every 21 days
- EC
Epirubicin 75mg/m2 IV D1
Cyclophosphamide 600mg/m2 IV D1
Cycled every 21 days
- AT
Doxorubicin 60mg/m2 IV D1 or 50mg/m2 IV D1
Paclitaxel 125-200 mg/m2 IV D1 or Docetaxel 75mg/m2 IV D1
Cycled every 21 days
- CMF
Cyclophosphamide 100mg/m2 PO D1-14
Methotrexate 40mg/m2 IV D1 & 8
5FU 600mg/m2 Iv D1 & *
Cycled every 28 days
- docetaxel/capecitabine
Docetaxel 75mg/m2 IV D1
Capecitabine 950mg/m2 PO bd 1-14
Cycled every 21 days
- GT
Paclitaxel 175mg/m2 IV D1
Gemcitabine 1250 mg/m2 IV D1 & 8 (following paclitaxel on D1)
Cycled every 21 days
e. Other combinations
- ixabepilone + capecitabine
Ixabepilone 40mg/m2 IV D1
Capecitabine 2000mg/m2 PO D1-14
Cycled every 21 days
f. Preferred first line agents for Her-2 positive disease: Trastuzumab 4 mg/kg IV D1 followed by 2mg/kg IV weekly or 8mg/kg IV D1 followed by 6mg/kg IV every 3 wks with:
- paclitaxel + carboplatin (PCH)
Carboplatin AUC of 6 IV D1
Paclitaxel 175mg/m2 IV D1
Cycled every 21 days
- weekly TCH chemotherapy
Paclitaxel 80mg/m2 IV D1, 8 & 15
Carboplatin AUC of 2 IV D1, 8 & 15
Cycled every 28 days
- paclitaxel 175mg/m2 IV D1 cycled every 21 days or 80-90mg/m2 IV weekly
- docetaxel 80-100mg/m2 IV D1 cycled every 21 days or 35mg/m2 IV infusion weekly
- vinorelbine 25mg/m2 IV weekly
- capecitabine 1000-1250mg/m2 PO bd D1-14 cycled every 21 days
g. Preferred agents for trastuzumab-exposed Her2-positive disease
- lapitinib 1250mg PO daily D1-21 + capecitabine 1000mg/m2 PO bd D1-14 cycled every 21 days
- trastuzumab + other first line agents
- trastuzumab + capecitabine
- trastuzumab + lapatinib (without cytotoxic therapy) 1000mg PO daily
(trastuzumab 4mg/kg IV D1 followed by 2mg/kg IV weekly or 8mg/kg IV D1 followed by 6mg/kg Iv every 3 wks)
Saturday, August 22, 2009
Breast cancer: adjuvant and neoadjuvant chemotherapy regimes, adjuvant endocrine therapy
3. Non-trastuzumab containing adjuvant regimens (NCCN)
A. Preferred
a. TAC (docetaxel/doxorubicin/cyclophosphamide)
docetaxel 75mg/m2 iv D1
doxorubicin 50mg/m2 iv D1
cyclophosphamide 500mg/m2 IV D1
cycled every 21 days for 6 cycles (all cycles with filgrastim support)
b. Dose-dense AC (doxorubicin/cyclophosphamide) followed by paclitaxel every 2 weeks
doxorubicin 60mg/m2 iv D1
cyclophosphamide 600mg/m2 iv D1
cycled every 14 days for 4 cycles
followed by paclitaxel 175mg/m2 by 3h iv infusion day 1
cycled every 14 days for 4 cycles
all cycles with filgrastim support
c. AC (doxorubicin/cyclophosphamide) followed by weekly paclitaxel
doxorubicin 60mg/m2 iv day 1
cyclophosphamide 600mg/m2 iv day 1
cycled every 21 days for 4 cycles
followed by paclitaxel 80mg/,2 by 1h IV infusion weekly for 12 wks
d. TC (docetaxel and cyclophosphamide)
docetaxel 75mg/m2 iv D1
cyclophosphamide 600mg/m2 iv D1
cycled every 21 days for 4 cycles
e. AC (doxorubicin/cyclophosphamide)
doxorubicin 60mg/m2 iv D1
cyclophosphamide 600mg/m2 iv D1
cycled every 21 days for 4 cycles
B. Others
a. FAC/CAF (fluorouracil/doxorubicin/cyclophosphamide)
i. FAC
5FU 500mg/m2 iv D1&8 or D1&4
Doxorubicin 50mg/m2 IV D1 or by 72h continuous infusion
Cyclophosphamide 500mg/m2 iv D1
Cycled every 21 days for 6 cycles
ii. CAF
cyclophosphamide 100mg/m2 iv D1
doxorubicin 30mg/m2 iv D1&8
5FU 500mg/m2 iv D1&8
Cycled every 28 days for 6 cycles
b. FEC/CEF (cyclophosphamide/epirubicin/fluorouracil)
i. FEC
cyclophosphamide 75mg/m2 PO D1-14
epirubicin 60mg/m2 iv D1&8
5FU 500mg/m2 iv D1&8
With cotrimoxazole support
Cycled every 28 days for 6 cycles
c. CMF (cyclophosphamide/methotrexae/fluorouracil)
Cyclophosphamide 100mg/m2 PO D1-14
Methotrexate 40mg/m2 iv D1&8
5FU 600mg/m2 IV D1&8
Cycled every 28 days for 6 cycles
d. AC followed by docetaxel every 3 weeks
doxorubicin 60mg/m2 D1
cyclophosphamide 600mg/m2 IV D1
followed by docetaxel 100mg/m2 IV on D1
cycled every 21 days for 4 cycles
e. AC followed by paclitaxel every 3 weeks
doxorubicin 60mg/m2 D1
cyclophosphamide 600mg/m2 IV D1
cycled every 21 days for 4 cycles
followed by paclitaxel 175-225 mg/m2 by 3h IV infusion on D1
cycled every 21 days for 4 cycles
f. EC (epirubicin/cyclophosphamide)
epirubicin 100mg/m2 iv D1
cyclophosphamide 830mg/m2 IV D1
cycled every 21 days for 8 cycles
g. Dose dense ATC:- A followed by T followed by C (doxorubicin followed by paclitaxel followed by cyclophosphamide) every 2 weekly regimen with filgrastim support
doxorubicin 60mg/m2 IV D1 cycled every 14 days for 4 cycles
followed by paclitaxel 175mg/m2 by 3h IV D1 cycled every 14 days for 4 cycles
followed by cyclophosphamide 600mg/m2 IV D1 cycled every 14 days for 4 cycles
h. FEC followed by T (docetaxel)
5FU 500mg/m2 IV D1
Epirubicin 100mg/m2 IV D1
Cyclophosphamide 500mg/m2 D1
Cycled every 21 days for 3 cycles
Followed by docetaxel 100mg/m2 D1 cycled every 21 days for 3 cycles
4. Trastuzumab containing regimens
A. Preferred adjuvant
a. AC followed by T + concurrent tastuzumab (doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab, various schedules)
doxorubicin 60mg/m2 iv D1
cyclophosphamide 600mg/m2 IV D1
cycled every 21 days for 4 cycles
followed by
paclitaxel 80mg/m2 by 1h IV weekly for 12 wks OR paclitaxel 175mg/m2 by 3h IV D1 cycled every 21 days for 4 cycles
with trastuzumab 4mg/kg IV with first dose of paclitaxel
followed by
trastuzumab 2mg/kg IV weekly to complete 1y OR 6mg/kg iv every 3 wk to complete 1y
(cardiac monitoring at baseline 3,6,9 mo)
b. Dose dense AC followed by paclitaxel chemotherapy (all cycles with filgrastim support)
AC as above but cycled every 14 days for 4 cycles
Followed by paclitaxel 175mg/m2 by 3h IV infusion D1 cycled every 14 days for 4 cycles
With trastuzumab 4mg/kg IV with first dose of paclitaxel
Followed by trastuzumab 2mg/kg IV weekly to complete 1y or 6mg/kg IV every 3 wk to complete 1y
(cardiac monitoring at baseline 3,6,9 mo)
c. TCH (docetaxel, carboplatin, trastuzumab)
docetaxel 75mg/m2 IV D1
followed by carboplatin AUC 6 IV D1
cycled every 21 days for 6 cycles
with trastuzumab 4mg/kg wk 1 followed by 2mg/kg for 17 wks followed by 6mg/kg every 3 wks to complete 1 y
(cardiac monitoring at baseline,3,6,9 mo)
B. Other adjuvant
a. Docetaxel + trastuzumab followed by FEC (fluorouracil/epirubicin/cyclophosphamide)
docetaxel 100mg/m2 by 1h IV D1 cycled every 21 days for 3 cycles
with trastuzumab 4mg/kg IV with first dose of docetaxel D1 followed by 2mg/kg IV weekly to complete 9 wks
followed by
5FU 600mg/m2 D1
Epirubicin 60mg/m2 D1
Cyclophosphamide 600mg/m2 D1
Cycled every 21 days for 3 cycles
(cardiac monitoring at baseline, after last FEC cycle, at 12 and 36 mo after chemotherapy)
b. Chemotherapy followed by trastuzumab sequentially
Approved adjuvant chemotherapy regimen at least 4 cycles followed by trastuzumab 8mg/kg IV times 1 dose followed by trastuzumab 6mg/kg IV every 21days for 1 y
(cardiac monitoring at baseline,3,6,9 mo)
c. AC followed by docetaxel + trastuzumab
doxorubicin 60mg/m2 IV D1
cyclophosphamide 600mg/m2 D1
cycled every 21 days for 4 cycles
with
trastuzumab 4mg/kg IV wk one followed by 2mg/kg IV weekly for 11 weeks followed by 6mg/kg every 21 days to complete 1y of trastuzumab therapy
(cardiac monitoring at baseline,3,6,9 mo)
C. Neoadjuvant
a. T (paclitaxel) + trastuzumab followed by CEF + trastuzumab
trastuzumab 4mg/kg IV for 1 dose beginning just prior to first dose of pacitaxel
followed by trastuzumab 2mg/kg IV weekly for 23 weeks
paclitaxel 225mg/m2 by 24h IV infusion every 21 dys for 4 cycles (alternatively paclitaxel 80mg/m2 by 1h IV infusion weekly for 12 wks)
followed by
5FU 500mg/m2 on D1 and 4
Epirubicin 75mg/m2 on D1
Cyclophosphamide 500mg/m2 on D1
Cycled every 21 days for 4 cycles
7. Adjuvant endocrine therapy
a. Premenopausal
- tamoxifen for 2-3 y +/- ovarian suppression/ablation
- complete 5y tamoxifen or after postmenopausal aromatase inhibitor 5y
b. Menopause – prior bilateral oopherectomy, age >= 60y, age <60y and amenorrhoeic 12 mo in absence of chemotherapy/tamoxifen/toremifene/ovarian suppression and FSH & estradiol in postmenopausal range, if taking tamoxifen or toreifene and age<60y then FSH & oestradiol in postmenopausal range)
A. Preferred
a. TAC (docetaxel/doxorubicin/cyclophosphamide)
docetaxel 75mg/m2 iv D1
doxorubicin 50mg/m2 iv D1
cyclophosphamide 500mg/m2 IV D1
cycled every 21 days for 6 cycles (all cycles with filgrastim support)
b. Dose-dense AC (doxorubicin/cyclophosphamide) followed by paclitaxel every 2 weeks
doxorubicin 60mg/m2 iv D1
cyclophosphamide 600mg/m2 iv D1
cycled every 14 days for 4 cycles
followed by paclitaxel 175mg/m2 by 3h iv infusion day 1
cycled every 14 days for 4 cycles
all cycles with filgrastim support
c. AC (doxorubicin/cyclophosphamide) followed by weekly paclitaxel
doxorubicin 60mg/m2 iv day 1
cyclophosphamide 600mg/m2 iv day 1
cycled every 21 days for 4 cycles
followed by paclitaxel 80mg/,2 by 1h IV infusion weekly for 12 wks
d. TC (docetaxel and cyclophosphamide)
docetaxel 75mg/m2 iv D1
cyclophosphamide 600mg/m2 iv D1
cycled every 21 days for 4 cycles
e. AC (doxorubicin/cyclophosphamide)
doxorubicin 60mg/m2 iv D1
cyclophosphamide 600mg/m2 iv D1
cycled every 21 days for 4 cycles
B. Others
a. FAC/CAF (fluorouracil/doxorubicin/cyclophosphamide)
i. FAC
5FU 500mg/m2 iv D1&8 or D1&4
Doxorubicin 50mg/m2 IV D1 or by 72h continuous infusion
Cyclophosphamide 500mg/m2 iv D1
Cycled every 21 days for 6 cycles
ii. CAF
cyclophosphamide 100mg/m2 iv D1
doxorubicin 30mg/m2 iv D1&8
5FU 500mg/m2 iv D1&8
Cycled every 28 days for 6 cycles
b. FEC/CEF (cyclophosphamide/epirubicin/fluorouracil)
i. FEC
cyclophosphamide 75mg/m2 PO D1-14
epirubicin 60mg/m2 iv D1&8
5FU 500mg/m2 iv D1&8
With cotrimoxazole support
Cycled every 28 days for 6 cycles
c. CMF (cyclophosphamide/methotrexae/fluorouracil)
Cyclophosphamide 100mg/m2 PO D1-14
Methotrexate 40mg/m2 iv D1&8
5FU 600mg/m2 IV D1&8
Cycled every 28 days for 6 cycles
d. AC followed by docetaxel every 3 weeks
doxorubicin 60mg/m2 D1
cyclophosphamide 600mg/m2 IV D1
followed by docetaxel 100mg/m2 IV on D1
cycled every 21 days for 4 cycles
e. AC followed by paclitaxel every 3 weeks
doxorubicin 60mg/m2 D1
cyclophosphamide 600mg/m2 IV D1
cycled every 21 days for 4 cycles
followed by paclitaxel 175-225 mg/m2 by 3h IV infusion on D1
cycled every 21 days for 4 cycles
f. EC (epirubicin/cyclophosphamide)
epirubicin 100mg/m2 iv D1
cyclophosphamide 830mg/m2 IV D1
cycled every 21 days for 8 cycles
g. Dose dense ATC:- A followed by T followed by C (doxorubicin followed by paclitaxel followed by cyclophosphamide) every 2 weekly regimen with filgrastim support
doxorubicin 60mg/m2 IV D1 cycled every 14 days for 4 cycles
followed by paclitaxel 175mg/m2 by 3h IV D1 cycled every 14 days for 4 cycles
followed by cyclophosphamide 600mg/m2 IV D1 cycled every 14 days for 4 cycles
h. FEC followed by T (docetaxel)
5FU 500mg/m2 IV D1
Epirubicin 100mg/m2 IV D1
Cyclophosphamide 500mg/m2 D1
Cycled every 21 days for 3 cycles
Followed by docetaxel 100mg/m2 D1 cycled every 21 days for 3 cycles
4. Trastuzumab containing regimens
A. Preferred adjuvant
a. AC followed by T + concurrent tastuzumab (doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab, various schedules)
doxorubicin 60mg/m2 iv D1
cyclophosphamide 600mg/m2 IV D1
cycled every 21 days for 4 cycles
followed by
paclitaxel 80mg/m2 by 1h IV weekly for 12 wks OR paclitaxel 175mg/m2 by 3h IV D1 cycled every 21 days for 4 cycles
with trastuzumab 4mg/kg IV with first dose of paclitaxel
followed by
trastuzumab 2mg/kg IV weekly to complete 1y OR 6mg/kg iv every 3 wk to complete 1y
(cardiac monitoring at baseline 3,6,9 mo)
b. Dose dense AC followed by paclitaxel chemotherapy (all cycles with filgrastim support)
AC as above but cycled every 14 days for 4 cycles
Followed by paclitaxel 175mg/m2 by 3h IV infusion D1 cycled every 14 days for 4 cycles
With trastuzumab 4mg/kg IV with first dose of paclitaxel
Followed by trastuzumab 2mg/kg IV weekly to complete 1y or 6mg/kg IV every 3 wk to complete 1y
(cardiac monitoring at baseline 3,6,9 mo)
c. TCH (docetaxel, carboplatin, trastuzumab)
docetaxel 75mg/m2 IV D1
followed by carboplatin AUC 6 IV D1
cycled every 21 days for 6 cycles
with trastuzumab 4mg/kg wk 1 followed by 2mg/kg for 17 wks followed by 6mg/kg every 3 wks to complete 1 y
(cardiac monitoring at baseline,3,6,9 mo)
B. Other adjuvant
a. Docetaxel + trastuzumab followed by FEC (fluorouracil/epirubicin/cyclophosphamide)
docetaxel 100mg/m2 by 1h IV D1 cycled every 21 days for 3 cycles
with trastuzumab 4mg/kg IV with first dose of docetaxel D1 followed by 2mg/kg IV weekly to complete 9 wks
followed by
5FU 600mg/m2 D1
Epirubicin 60mg/m2 D1
Cyclophosphamide 600mg/m2 D1
Cycled every 21 days for 3 cycles
(cardiac monitoring at baseline, after last FEC cycle, at 12 and 36 mo after chemotherapy)
b. Chemotherapy followed by trastuzumab sequentially
Approved adjuvant chemotherapy regimen at least 4 cycles followed by trastuzumab 8mg/kg IV times 1 dose followed by trastuzumab 6mg/kg IV every 21days for 1 y
(cardiac monitoring at baseline,3,6,9 mo)
c. AC followed by docetaxel + trastuzumab
doxorubicin 60mg/m2 IV D1
cyclophosphamide 600mg/m2 D1
cycled every 21 days for 4 cycles
with
trastuzumab 4mg/kg IV wk one followed by 2mg/kg IV weekly for 11 weeks followed by 6mg/kg every 21 days to complete 1y of trastuzumab therapy
(cardiac monitoring at baseline,3,6,9 mo)
C. Neoadjuvant
a. T (paclitaxel) + trastuzumab followed by CEF + trastuzumab
trastuzumab 4mg/kg IV for 1 dose beginning just prior to first dose of pacitaxel
followed by trastuzumab 2mg/kg IV weekly for 23 weeks
paclitaxel 225mg/m2 by 24h IV infusion every 21 dys for 4 cycles (alternatively paclitaxel 80mg/m2 by 1h IV infusion weekly for 12 wks)
followed by
5FU 500mg/m2 on D1 and 4
Epirubicin 75mg/m2 on D1
Cyclophosphamide 500mg/m2 on D1
Cycled every 21 days for 4 cycles
7. Adjuvant endocrine therapy
a. Premenopausal
- tamoxifen for 2-3 y +/- ovarian suppression/ablation
- complete 5y tamoxifen or after postmenopausal aromatase inhibitor 5y
b. Menopause – prior bilateral oopherectomy, age >= 60y, age <60y and amenorrhoeic 12 mo in absence of chemotherapy/tamoxifen/toremifene/ovarian suppression and FSH & estradiol in postmenopausal range, if taking tamoxifen or toreifene and age<60y then FSH & oestradiol in postmenopausal range)
Breast cancer: background
1. Staging/investigation
a. bloods + LFT, ALP
b. diagnostic bilateral mammogram, ultrasound
c. determination of ER/PR/Her2 status
d. KIV breast MRI
e. bone scan (localized symptoms, elevated ALP, T3N1M0)
f. abdominal +/- pelvic CT/US/MRI (elevated ALP, abnormal LFT, abdominal symptoms, abnormal physical examination of abdomen or pelvis, T3N1M0)
g. chest imaging (if pulmonary symptoms present)
h. genetic counseling if high risk
i. tamoxifen: annual gynae assessment if uterus present
j. aromatase inhibitor/ovarian failure: BMD (also remember to give calcium and vit D tabs)
2. JH guidelines for metastatic breast CA
a. AC – Taxol – Gem/Cis – Femara – Xeloda
b. ECF, Epirubicin, 5FU, cyclophosphamide
c. Aromatase inhibitors (arimidex)
a. bloods + LFT, ALP
b. diagnostic bilateral mammogram, ultrasound
c. determination of ER/PR/Her2 status
d. KIV breast MRI
e. bone scan (localized symptoms, elevated ALP, T3N1M0)
f. abdominal +/- pelvic CT/US/MRI (elevated ALP, abnormal LFT, abdominal symptoms, abnormal physical examination of abdomen or pelvis, T3N1M0)
g. chest imaging (if pulmonary symptoms present)
h. genetic counseling if high risk
i. tamoxifen: annual gynae assessment if uterus present
j. aromatase inhibitor/ovarian failure: BMD (also remember to give calcium and vit D tabs)
2. JH guidelines for metastatic breast CA
a. AC – Taxol – Gem/Cis – Femara – Xeloda
b. ECF, Epirubicin, 5FU, cyclophosphamide
c. Aromatase inhibitors (arimidex)
Nasopharyngeal carcinoma (NPC)
1. Staging
a. Chest imaging
b. MRI with gadolinium of nasopharnx and base of skull to clavicles and/or CT with contrast or PET CT and CT with contrast
c. Dental evaluation
d. Speech and swallowing evaluation
e. Imaging for distant mets (chest, liver, bone) for WHO class 2-3/N2-3 disease (may include PET and/or CT
2. JH guidelines
a. Neoadjuvant
- 3 cycles of 3 weeks: D1 cisplatin 100mg/m2 and bleomycin 15mg then D2-5 bleomycin 12mg/m2
- 2-3 cycles of 3 weeks: D1 cisplatin 60mg/m2 and epirubicin 110mg/m2 D1
3. Treatment
a. T1, N0, M0 and T2a, N0, M0: definitive RT to nasopharyny and elective RT to neck
b. T1-T2a, N1-3; T2b-T4, any N:
Cisplatin 100mg/m2 on D1/22/43 of cisplatin 40mg/m2 every wk + RT (>= 70 Gy) to primary and gross nodal disease and bilateral neck: >= 50 Gy
= followed by=
Cisplatin 80 mg/m2 D1 + 5FU 1000mg/m2 Ca x 4 days, repeat every 4 wk x 3 courses
= KIV=
Neck dissection if residual tumour
c. Metastatic: Platinum based combination chemotherapy – if complete response, definitive RT to primary and neck
d. Unresectable T4b: PS0-1 concurrent cisplatin chemoRT or induction chemotherapy flw by chemoRT, PS2 definitive RT +/- concurrent systemic therapy, PS3 definitive RT or BSC = neck dissection if feasible and primary site controlled
4. Regimens
a. Chemoradiation followed by adjuvant chemotherapy: cisplatin + RT followed by cisplatin/5FU
b. Recurrent, unresectable or metastatic (incurable)
i. Combination therapy
- cisplatin/carboplatin + 5FU +/- cetuximab
- cisplatin or carboplatin + docetaxel or paclitaxel
- cisplatin/cetuximab
ii. Single agent: cisplatin, carboplatin, paclitaxel, docetaxel, 5FU, methotrexate, ifosfamide, bleomycin, gemcitabine (NPC), cetuximab
4. Follow up
a. Physical exam y1 q1-3mo, y2 q2-4 mo, y3-5 q4-6mo, >5y 6-12 mo
b. Post-treatment baseline imaging of primary and neck recommended within 6 mo of treatment, reimaging as indicated
c. Chest imaging as clinically indicated
d. TSH every 6-12 mo if neck irradiated
e. Speech, hearing and swallowing evaluation and rehab, dental evaluation
a. Chest imaging
b. MRI with gadolinium of nasopharnx and base of skull to clavicles and/or CT with contrast or PET CT and CT with contrast
c. Dental evaluation
d. Speech and swallowing evaluation
e. Imaging for distant mets (chest, liver, bone) for WHO class 2-3/N2-3 disease (may include PET and/or CT
2. JH guidelines
a. Neoadjuvant
- 3 cycles of 3 weeks: D1 cisplatin 100mg/m2 and bleomycin 15mg then D2-5 bleomycin 12mg/m2
- 2-3 cycles of 3 weeks: D1 cisplatin 60mg/m2 and epirubicin 110mg/m2 D1
3. Treatment
a. T1, N0, M0 and T2a, N0, M0: definitive RT to nasopharyny and elective RT to neck
b. T1-T2a, N1-3; T2b-T4, any N:
Cisplatin 100mg/m2 on D1/22/43 of cisplatin 40mg/m2 every wk + RT (>= 70 Gy) to primary and gross nodal disease and bilateral neck: >= 50 Gy
= followed by=
Cisplatin 80 mg/m2 D1 + 5FU 1000mg/m2 Ca x 4 days, repeat every 4 wk x 3 courses
= KIV=
Neck dissection if residual tumour
c. Metastatic: Platinum based combination chemotherapy – if complete response, definitive RT to primary and neck
d. Unresectable T4b: PS0-1 concurrent cisplatin chemoRT or induction chemotherapy flw by chemoRT, PS2 definitive RT +/- concurrent systemic therapy, PS3 definitive RT or BSC = neck dissection if feasible and primary site controlled
4. Regimens
a. Chemoradiation followed by adjuvant chemotherapy: cisplatin + RT followed by cisplatin/5FU
b. Recurrent, unresectable or metastatic (incurable)
i. Combination therapy
- cisplatin/carboplatin + 5FU +/- cetuximab
- cisplatin or carboplatin + docetaxel or paclitaxel
- cisplatin/cetuximab
ii. Single agent: cisplatin, carboplatin, paclitaxel, docetaxel, 5FU, methotrexate, ifosfamide, bleomycin, gemcitabine (NPC), cetuximab
4. Follow up
a. Physical exam y1 q1-3mo, y2 q2-4 mo, y3-5 q4-6mo, >5y 6-12 mo
b. Post-treatment baseline imaging of primary and neck recommended within 6 mo of treatment, reimaging as indicated
c. Chest imaging as clinically indicated
d. TSH every 6-12 mo if neck irradiated
e. Speech, hearing and swallowing evaluation and rehab, dental evaluation
Small cell lung CA
Small cell lung cancer
1. Staging/Inx
- CXR (optional)
- CT chest/liver/adrenal
- head MRI/CT
- bone scan vs PET scan
- LDH, Ca, LFT
a. Limited stage
- BMA
- thoracocentesis/thoracoscopy
- pulmonary function tests
- bone XR of areas showing abnormal uptake on bone/PET scan; if negative/inconclusive MRI bony lesions
2. Initial treatment
a. T1-2, mediastinal staging negative: lobectomy and mediastinal N0 chemotherapy, N+ concurrent chemoRT
b. concurrent chemoRT for PS 0-2, chemo+/-RT for poor PS due to SCLC
c. Extensive stage: not localised - combination chemotherapy, SVCO/lobar obs/bone mets/SC compression - chemo +/- RT to site, brain mets - WBRT
3. After initial treatment
- CR/PR/radiation scarring/less 10% mass: PCI
- follow-up 12-3mo during y1, every 3-4 mo dring y2-3, every 4-6mo during y4-5, then annually with bloods and chest imaging
- new pulm nodule after 2y - potential new primary
4. Chemotherapy as primary therapy
a. Limited stage
- cisplatin 60mg/m2 D1 and etoposide 120mg/m2 D1,2,3 x 4 cycles (recommended for chemoRT)
- carboplatin AUC 5-6 day 1 and etoposide 100mg/m2 days 1,2,3 x 4cycles
b. Extensive stage
- cisplatin 75mg/m2 D1 and etoposide 100mg/m2 D1,2,3 x 4-6 cycles
- cisplatin 80mg/m2 D1 and etoposide 100mg/m2 D1,2,3
- cisplatin 25mg/m2 D1,2,3 and etoposide 100mg/m2 days 1,2,3
- carboplatin AUC 5-6 D1, etoposide 100mg/m2 D1,2,3 x 4-6 cycles
- cisplatin 60mg/m2 on D14, irinotecan 60mg/m2 on D1/8/15
- carboplatin AUC 5 and irinotecan 50mg/m2 D1,8,15
- cyclophosphamide 1000mg/m2 D1 and doxorubicin 45mg/m2 D1 and vincristine 1.4mg/m2 D1
c. Subsequent chemotherapy
- clinical trial preferred
- relapse <2-3mo, PS 0-2: ifosfamide, paclitacel, docetaxel, gemcitabine, irinotecan, topotecan
- relapse >2-3mo up to 6mo: topotecan, irinotecan, cyclophosphamide/doxorubicin/vincristine (CAV), gemcitabine, paclitaxel, docetaxel, oral etoposide, vinorelbine
- relapse >6mo: original regimen
1. Staging/Inx
- CXR (optional)
- CT chest/liver/adrenal
- head MRI/CT
- bone scan vs PET scan
- LDH, Ca, LFT
a. Limited stage
- BMA
- thoracocentesis/thoracoscopy
- pulmonary function tests
- bone XR of areas showing abnormal uptake on bone/PET scan; if negative/inconclusive MRI bony lesions
2. Initial treatment
a. T1-2, mediastinal staging negative: lobectomy and mediastinal N0 chemotherapy, N+ concurrent chemoRT
b. concurrent chemoRT for PS 0-2, chemo+/-RT for poor PS due to SCLC
c. Extensive stage: not localised - combination chemotherapy, SVCO/lobar obs/bone mets/SC compression - chemo +/- RT to site, brain mets - WBRT
3. After initial treatment
- CR/PR/radiation scarring/less 10% mass: PCI
- follow-up 12-3mo during y1, every 3-4 mo dring y2-3, every 4-6mo during y4-5, then annually with bloods and chest imaging
- new pulm nodule after 2y - potential new primary
4. Chemotherapy as primary therapy
a. Limited stage
- cisplatin 60mg/m2 D1 and etoposide 120mg/m2 D1,2,3 x 4 cycles (recommended for chemoRT)
- carboplatin AUC 5-6 day 1 and etoposide 100mg/m2 days 1,2,3 x 4cycles
b. Extensive stage
- cisplatin 75mg/m2 D1 and etoposide 100mg/m2 D1,2,3 x 4-6 cycles
- cisplatin 80mg/m2 D1 and etoposide 100mg/m2 D1,2,3
- cisplatin 25mg/m2 D1,2,3 and etoposide 100mg/m2 days 1,2,3
- carboplatin AUC 5-6 D1, etoposide 100mg/m2 D1,2,3 x 4-6 cycles
- cisplatin 60mg/m2 on D14, irinotecan 60mg/m2 on D1/8/15
- carboplatin AUC 5 and irinotecan 50mg/m2 D1,8,15
- cyclophosphamide 1000mg/m2 D1 and doxorubicin 45mg/m2 D1 and vincristine 1.4mg/m2 D1
c. Subsequent chemotherapy
- clinical trial preferred
- relapse <2-3mo, PS 0-2: ifosfamide, paclitacel, docetaxel, gemcitabine, irinotecan, topotecan
- relapse >2-3mo up to 6mo: topotecan, irinotecan, cyclophosphamide/doxorubicin/vincristine (CAV), gemcitabine, paclitaxel, docetaxel, oral etoposide, vinorelbine
- relapse >6mo: original regimen
Non Small Cell Lung Ca (NSCLC)
Non Small Cell Lung CA (NSCLC)
1. Staging and Inx
- CT chest and upper adrenals
- pulmonary function tests
- bronchoscopy
- mediastinoscopy
- PET CT
- brain MRI (Stage II onwards)
- MRI of spine + thoracic inlet for superior sulcus lesions abutting spine/subclavian vessels (Stage III)
- pathologic confirmation of N3 disease in Stage IIIB: mediastinoscopy/supraclavicular lymph node biopsy, thoracoscopy, needle biopsy, EUS/EBUS biopsy
- pleural/pericardial effusion: thoracocentesis/pericardiocentesis if indicated +/- thoracoscopy if thoracentesis indeterminate
2. JH guidelines
a. Gem/Carbo
b. Alimta
c. Docetaxel
d. Vinorelbine/cisplatin
3. Adjuvant regimens
a. cisplatin 50mg/m2 D1&8, vinorelbine 25mg/m2 D1/8/15/22 every 28 days for 4 cycles
b. cisplatin 100mg/m2 D1, vinorelbine 30mg/m2 D1/8/15/22 every 28 days for 4 cycles
c. cisplatin 75-80mg/m2 D1; vinorelbine 25-30mg/m2 D1+8 every 21 days for 4 cycles
d. cisplatin 100mg/m2 D1, etoposide 100mg/m2 D1-3 every 28 days for 4 cycles
e. cisplatin 80mg/m2 on D1/22/43/62, vinblastine 4mg/m2 D1/8/15/22 then every 2 wks after day 43 every 21 days for 4 cycles
f. cisplatin 80mg/m2 D1, gemcitabine 1000mg/m2 on D1&8
g. cisplatin 75mg/m2, docetaxel 75mg/m2 every 21 days
h. comorbidities/unable to tolerate cisplatin: paclitaxel 200mg/m2 D1, carboplatin AUC6 D1
4. Concurrent chemoRT
a. cisplatin 50mg/m2 D1/8/29/36, etoposide 50mg/m2 D1-5, 29-33, concurrent thoracic RT (total dose 61 Gy)
b. cisplatin 100mg/m2 D1 & 29, vinblastine 5mg/m2/weekly x 5, concurrent thoracic RT 60Gy (preferred)
c. paclitaxel 45-50mg/m2 weekly over 1 hour, caarboplatin AUC = 2mg/mL/min over 30min weekly, concurrent thoracic RT 63 Gy/7wks/34 fractions
5. Sequential chemoRT
a. cisplatin 100mg/m2 on D1 & 29, vinblastine 5mg/m2/weekly on D1/8/15/22/29, followed by RT with 60Gy in 30 fractions beginning on day 50
b. paclitaxel 200mg/m2 every 3 weeks over 3 hours, 2 cycles and carboplatin AUC 6, 2 cycles followed by thoracic RT 63 Gy beginning day 42
6. Concurrent chemoRT
a. cisplatin 50mg/m2 D1/8/29/36, etoposide 50mg/m2 days 1-5 and 29-33, concurrent thoracic RT (total dose, 61 Gy), docetaxel started 4-6 wk after chemoradiation at initial dose of 75mg/m2 x 3 doses every 3 weeks
b. paclitaxel 45-50mg/m2 weekly, carboplatin AUC2, concurrent thoracic RT 63Gy, followed by 2 cycles of paclitaxel 200mg/m2 and carboplatin AUC6
7. Therapy for recurrence and mets
a. PS 0-1: chemotherapy +/- bevaxizumab, cisplatin/pemetrexed, cetuximab/vinorelbine/cisplatin
b. PS 2: cetuximab/vinorelbine/cisplatin or chemotherapy
(tumour response evaluation – cycle 2 – tumour response/SD: 4-6 cycles total or pemetrexed for non-squamous – progression)
8. Progressive disease
a. Second line: docetaxel/pemetrexed/erlotinib
b. Third line: Erlotinib
9. IHC markers
- TTF-1= primary lung carcinoma
- pulmonary adenocarcinoma: CK7+, CK20-
- CDX-2: mets GI malignancies
- PSA, prostatic acid phosphatase
- gross cystic disease fluid protein 15: adenocarcinoma of breasy origin
- chromogranin, synaptophysin: neuroendocrine tumour of lung i.e. carcinoid
- adenocarcinoma: CEA, B72.3, Ber-EP4, MOC31
- mesothelioma: WT-1, calretinin, D2-40, cytokeratin 5/6
- nonmucinous BAC: TTF1, CK7+, CK20-
- aberrant mucinous BAC: CK20/7+, TTF1 negative
- K-ras mutations: intrinsic TKI resistance
1. Staging and Inx
- CT chest and upper adrenals
- pulmonary function tests
- bronchoscopy
- mediastinoscopy
- PET CT
- brain MRI (Stage II onwards)
- MRI of spine + thoracic inlet for superior sulcus lesions abutting spine/subclavian vessels (Stage III)
- pathologic confirmation of N3 disease in Stage IIIB: mediastinoscopy/supraclavicular lymph node biopsy, thoracoscopy, needle biopsy, EUS/EBUS biopsy
- pleural/pericardial effusion: thoracocentesis/pericardiocentesis if indicated +/- thoracoscopy if thoracentesis indeterminate
2. JH guidelines
a. Gem/Carbo
b. Alimta
c. Docetaxel
d. Vinorelbine/cisplatin
3. Adjuvant regimens
a. cisplatin 50mg/m2 D1&8, vinorelbine 25mg/m2 D1/8/15/22 every 28 days for 4 cycles
b. cisplatin 100mg/m2 D1, vinorelbine 30mg/m2 D1/8/15/22 every 28 days for 4 cycles
c. cisplatin 75-80mg/m2 D1; vinorelbine 25-30mg/m2 D1+8 every 21 days for 4 cycles
d. cisplatin 100mg/m2 D1, etoposide 100mg/m2 D1-3 every 28 days for 4 cycles
e. cisplatin 80mg/m2 on D1/22/43/62, vinblastine 4mg/m2 D1/8/15/22 then every 2 wks after day 43 every 21 days for 4 cycles
f. cisplatin 80mg/m2 D1, gemcitabine 1000mg/m2 on D1&8
g. cisplatin 75mg/m2, docetaxel 75mg/m2 every 21 days
h. comorbidities/unable to tolerate cisplatin: paclitaxel 200mg/m2 D1, carboplatin AUC6 D1
4. Concurrent chemoRT
a. cisplatin 50mg/m2 D1/8/29/36, etoposide 50mg/m2 D1-5, 29-33, concurrent thoracic RT (total dose 61 Gy)
b. cisplatin 100mg/m2 D1 & 29, vinblastine 5mg/m2/weekly x 5, concurrent thoracic RT 60Gy (preferred)
c. paclitaxel 45-50mg/m2 weekly over 1 hour, caarboplatin AUC = 2mg/mL/min over 30min weekly, concurrent thoracic RT 63 Gy/7wks/34 fractions
5. Sequential chemoRT
a. cisplatin 100mg/m2 on D1 & 29, vinblastine 5mg/m2/weekly on D1/8/15/22/29, followed by RT with 60Gy in 30 fractions beginning on day 50
b. paclitaxel 200mg/m2 every 3 weeks over 3 hours, 2 cycles and carboplatin AUC 6, 2 cycles followed by thoracic RT 63 Gy beginning day 42
6. Concurrent chemoRT
a. cisplatin 50mg/m2 D1/8/29/36, etoposide 50mg/m2 days 1-5 and 29-33, concurrent thoracic RT (total dose, 61 Gy), docetaxel started 4-6 wk after chemoradiation at initial dose of 75mg/m2 x 3 doses every 3 weeks
b. paclitaxel 45-50mg/m2 weekly, carboplatin AUC2, concurrent thoracic RT 63Gy, followed by 2 cycles of paclitaxel 200mg/m2 and carboplatin AUC6
7. Therapy for recurrence and mets
a. PS 0-1: chemotherapy +/- bevaxizumab, cisplatin/pemetrexed, cetuximab/vinorelbine/cisplatin
b. PS 2: cetuximab/vinorelbine/cisplatin or chemotherapy
(tumour response evaluation – cycle 2 – tumour response/SD: 4-6 cycles total or pemetrexed for non-squamous – progression)
8. Progressive disease
a. Second line: docetaxel/pemetrexed/erlotinib
b. Third line: Erlotinib
9. IHC markers
- TTF-1= primary lung carcinoma
- pulmonary adenocarcinoma: CK7+, CK20-
- CDX-2: mets GI malignancies
- PSA, prostatic acid phosphatase
- gross cystic disease fluid protein 15: adenocarcinoma of breasy origin
- chromogranin, synaptophysin: neuroendocrine tumour of lung i.e. carcinoid
- adenocarcinoma: CEA, B72.3, Ber-EP4, MOC31
- mesothelioma: WT-1, calretinin, D2-40, cytokeratin 5/6
- nonmucinous BAC: TTF1, CK7+, CK20-
- aberrant mucinous BAC: CK20/7+, TTF1 negative
- K-ras mutations: intrinsic TKI resistance
Cheatsheet #1: AIDS-related malignancies - Kaposi sarcoma and Non-Hodgkin lymphoma
Kaposi sarcoma
1. ABV: doxorubicin 20mg/m2 iv D1, bleomycin 10mg/m2 iv D1, vincristine 1mg iv D1 repeat cycle every 14d
2. BV: bleomycin 15 IU/m2 iv D1, vincristine 2mg IV D1. Repeat cycle every 3 wk
3. Daunoxome: liposomal daunorubicin 40mg/m2 iv D1. Repeat cycle every 2 wk
4. Docetaxel: Docetaxel 25mg/m2 iv D1 repeat cycle weekly x 8
5. Doxil: liposomal doxorubicin 20mg/m2 iv D1 repeat cycle every 3 wk
6. Paclitaxel: paclitaxel 100mg/m2 iv over 3h D1 repeat cycle every 2 wk
7. Vinorelbine: vinorelbine 30mg/m2 iv D1 repeat cycle every 14 days
Non-Hodgkin’s lymphoma
1. CDE:
Cyclophosphamide 187.5-200mg/m2/d CIVI D1-4
Doxorubicin 12.5mg/m2/d CIVI D1-4
Etoposide 60mg/m2/d CIVI D1-4
Repeat cycle every 28d
2. CHOP
Cyclophosphamide750mg/m2 iv D1
Doxorubicin 50mg/m2 iv D1
Vincristine 1.4mg/m2 D1 (maximum dose 2mg)
Prednisone 100mg po daily D1-5
Repeat cycle every 21d
3. CODOX-M/IVAC
a. Low risk patients only: CODOX-M only
Cyclophosphamide 800mg/m2 iv D1
Cyclophosphamide 200mg/m2 iv D2-5
Doxorubicin 40mg/m2 iv D1
Vincristine 1.5mg/m2 iv D1 and 8 (cycle 1)
Vincristine 1.5mg/m2 iv D1/8/15 (cycle 2)
Methoterxate 1200mg/m2 iv over 1h followed by 240mg/m2/h x 23 h with leucovorin
Cytarabine 70mg intrathecal (IT) on D1 and 3
Methotrexate 12mg IT on day 15
b. High risk patients:
i. CODOX-M alternate with IVAC
Cyclophosphamide 800mg/m2 iv D1
Cyclophosphammide 200mg/m2 iv D1
Vincristine 1.5mg/m2 iv D1 & 8 (cycle 1)
Vincristine 1.5mg/m2 iv on D1/8/15 (cycle 2)
Methotrexate 1200mg/m2 iv over 1h followed by 240mg/m2/h x 23h with leucovorin
Cytarabine 70mg IT on D1&3
Methotrexate 12mg IT on D15
ii. IVAC alternate with CODOX-M
Ifosfamide 1500mg/m2 iv on D1-5 (with Mesna)
Etoposide 60mg/m2 iv on D1-5
Cytarabine 2000mg/m2 iv q12h x 4 on D1 and 2g/m2 iv on D1/8/15 (cycle 2)
Methotrexate 12mg IT on day 5
4. Dose adjusted EPOCH
Etoposide 50mg/m2/d CIVI on D1-4
Doxorubicin 10mg/m2/d CIVI on D1-4
Vincristine 0.4mg/m2/d CIVI on D1-4
Cyclophosphamide (cycle 1) 375mg/m2 iv on D5 (CD4+ cells >= 100/mm3), 187mg/m2 iv on D5 (CD4+ cells <100/mm3)
Cyclophosphamide (subsequent cycles) increase by 187mg/m2 if nadir ANC>500/microL; decrease by 187mg/m2 if nadir ANC<500/microL or PLT<250k/microL
Prednisolone 60mg/m2/d PO daily on D1-5
Repeat cycle q21d
5. EPOCH
Etoposide 50mg/m2/d CIVI on D1-4
Doxorubicin 10mg/m2/d CIVI on D1-4
Vincristine 0.4mg/m2/d CIVI on D1-4
Cyclophosphamide 750mg/m2 iv D5
Prednisone 60mg/m2/d PO daily D1-5
Repeat cycle every 21 days
6. Hyper-CVAD
Odd numbered cycles:
Cyclophosphamide 300mg/m2 iv q12h x 6 starting D1
Mesna 600mg/m2/d CIVI daily x 3d
Vincristine 2mg iv on D4 and 11
Doxorubicin 50mg/m2 iv on day 4
Dexamethasone 40mg iv/po on D1-4 and 11-14
Even numbered cycles:
Methotrexate 1000mg/m2 CIVI D1
Cytarabine 3000mg/m2 iv q12h x 4 on D2&3
Leucovorin 50mg iv x 1 starting 12h after completion of methotrexate followed by 15mg iv q6h until methotrexate level <0.1mM
7. m-BACOD
Methotrexate 200mg/m2 iv on day 15
Bleomycin 4U/m2 iv on D1
Doxorubicin 25mg/m2 iv on D1
Cyclophosphamide 300mg/m2 iv on D1
Vincristine 1.4mg/m2 iv on D1
Dexamethasone 3mg/m2 PO daily on D1-5
Cytarabine 50mg IT on D1/8/15/22
8. m-CHOP
Cyclophosphamide 375mg/m2 iv on D1
Doxorubicin 25mg/m2 iv on D1
Vincristine 1.4mg/m2 (maximum dose 2mg) iv on D1
Prednisone 100mg PO daily D1-5
1. ABV: doxorubicin 20mg/m2 iv D1, bleomycin 10mg/m2 iv D1, vincristine 1mg iv D1 repeat cycle every 14d
2. BV: bleomycin 15 IU/m2 iv D1, vincristine 2mg IV D1. Repeat cycle every 3 wk
3. Daunoxome: liposomal daunorubicin 40mg/m2 iv D1. Repeat cycle every 2 wk
4. Docetaxel: Docetaxel 25mg/m2 iv D1 repeat cycle weekly x 8
5. Doxil: liposomal doxorubicin 20mg/m2 iv D1 repeat cycle every 3 wk
6. Paclitaxel: paclitaxel 100mg/m2 iv over 3h D1 repeat cycle every 2 wk
7. Vinorelbine: vinorelbine 30mg/m2 iv D1 repeat cycle every 14 days
Non-Hodgkin’s lymphoma
1. CDE:
Cyclophosphamide 187.5-200mg/m2/d CIVI D1-4
Doxorubicin 12.5mg/m2/d CIVI D1-4
Etoposide 60mg/m2/d CIVI D1-4
Repeat cycle every 28d
2. CHOP
Cyclophosphamide750mg/m2 iv D1
Doxorubicin 50mg/m2 iv D1
Vincristine 1.4mg/m2 D1 (maximum dose 2mg)
Prednisone 100mg po daily D1-5
Repeat cycle every 21d
3. CODOX-M/IVAC
a. Low risk patients only: CODOX-M only
Cyclophosphamide 800mg/m2 iv D1
Cyclophosphamide 200mg/m2 iv D2-5
Doxorubicin 40mg/m2 iv D1
Vincristine 1.5mg/m2 iv D1 and 8 (cycle 1)
Vincristine 1.5mg/m2 iv D1/8/15 (cycle 2)
Methoterxate 1200mg/m2 iv over 1h followed by 240mg/m2/h x 23 h with leucovorin
Cytarabine 70mg intrathecal (IT) on D1 and 3
Methotrexate 12mg IT on day 15
b. High risk patients:
i. CODOX-M alternate with IVAC
Cyclophosphamide 800mg/m2 iv D1
Cyclophosphammide 200mg/m2 iv D1
Vincristine 1.5mg/m2 iv D1 & 8 (cycle 1)
Vincristine 1.5mg/m2 iv on D1/8/15 (cycle 2)
Methotrexate 1200mg/m2 iv over 1h followed by 240mg/m2/h x 23h with leucovorin
Cytarabine 70mg IT on D1&3
Methotrexate 12mg IT on D15
ii. IVAC alternate with CODOX-M
Ifosfamide 1500mg/m2 iv on D1-5 (with Mesna)
Etoposide 60mg/m2 iv on D1-5
Cytarabine 2000mg/m2 iv q12h x 4 on D1 and 2g/m2 iv on D1/8/15 (cycle 2)
Methotrexate 12mg IT on day 5
4. Dose adjusted EPOCH
Etoposide 50mg/m2/d CIVI on D1-4
Doxorubicin 10mg/m2/d CIVI on D1-4
Vincristine 0.4mg/m2/d CIVI on D1-4
Cyclophosphamide (cycle 1) 375mg/m2 iv on D5 (CD4+ cells >= 100/mm3), 187mg/m2 iv on D5 (CD4+ cells <100/mm3)
Cyclophosphamide (subsequent cycles) increase by 187mg/m2 if nadir ANC>500/microL; decrease by 187mg/m2 if nadir ANC<500/microL or PLT<250k/microL
Prednisolone 60mg/m2/d PO daily on D1-5
Repeat cycle q21d
5. EPOCH
Etoposide 50mg/m2/d CIVI on D1-4
Doxorubicin 10mg/m2/d CIVI on D1-4
Vincristine 0.4mg/m2/d CIVI on D1-4
Cyclophosphamide 750mg/m2 iv D5
Prednisone 60mg/m2/d PO daily D1-5
Repeat cycle every 21 days
6. Hyper-CVAD
Odd numbered cycles:
Cyclophosphamide 300mg/m2 iv q12h x 6 starting D1
Mesna 600mg/m2/d CIVI daily x 3d
Vincristine 2mg iv on D4 and 11
Doxorubicin 50mg/m2 iv on day 4
Dexamethasone 40mg iv/po on D1-4 and 11-14
Even numbered cycles:
Methotrexate 1000mg/m2 CIVI D1
Cytarabine 3000mg/m2 iv q12h x 4 on D2&3
Leucovorin 50mg iv x 1 starting 12h after completion of methotrexate followed by 15mg iv q6h until methotrexate level <0.1mM
7. m-BACOD
Methotrexate 200mg/m2 iv on day 15
Bleomycin 4U/m2 iv on D1
Doxorubicin 25mg/m2 iv on D1
Cyclophosphamide 300mg/m2 iv on D1
Vincristine 1.4mg/m2 iv on D1
Dexamethasone 3mg/m2 PO daily on D1-5
Cytarabine 50mg IT on D1/8/15/22
8. m-CHOP
Cyclophosphamide 375mg/m2 iv on D1
Doxorubicin 25mg/m2 iv on D1
Vincristine 1.4mg/m2 (maximum dose 2mg) iv on D1
Prednisone 100mg PO daily D1-5
Rectal CA
1. Staging
a. Colonoscopy
b. Rigid proctoscopy
c. Chest/abdominal/pelvic CT
d. CEA
e. EUS or endorectal or pelvic MRI
2. JH guidelines
a. ChemoRT
b. XELOX
c. XELIRI
3. Adjuvant therapy
a. Post-operative adjuvant chemotherapy for patients receiving preoprerative chemotherapy/RT
- 5FU 380mg/m2/day on days 1-5 +/- leucovorin iv 20mg/m2 on days 1-5 q28d x 4 cycles
- 5FU 500mg/m2 iv bolus injection 1h after the start of leucovorin infusion, once a wk for 6wk x 3 cycles, leucovorin 500mg/m2 iv over 2h once a wk for 6 weeks x 3 cycles (a cycle is comprised of 6wk followed by 2 wks of rest)
b. Post-operative adjuvant regimens for patients not receiving preoperative therapy
- 5FU + leucovorin x 1 cycle, then concurrent chemotherapy/XRT then 5FU/leucovorin x 2 cycles
(5FU 500mg/m2 iv bolus injection 1h after start of leucovorin infusion, once a wk for 6 wks + leucovorin 500mg/m2 IV over 2h once a wk for 6 wks. A cycle is 6 wks followed by 2 wks of rest)
- 5FU +/- leucovorin x 2 cycles then concurrent chemoRT then 5FU +/- leucovorin x 2 cycles (5FU 425mg/m2/day and leucovorin 20mg/m2/d, days 1-5 and 29-33 before RT. After RT the regimen is 5FU 380mg/m2/d and leucovorin 20mg/m2/day for 5 consecutive days x 2 cycles)
- FOLFOX
FOLFOX 4 (oxaliplatin 85mg/m2 IV over 2h D1, leucovorin 200mg/m2 IV over 2h D1&2, followed on D1 and 2 by 5FU 400mg/m2 iv bolus then 600mg/m2 iv over 22h continuous infusion; repeat q2w to total of 6 mo perioperative therapy)
mFOLFOX 6 (oxaliplatin 85mg/m2 IV over 2h D1 and leucovorin 400mg/m2 IV over 2h D1, 5FU 400mg/m2 IV bolus on D1 then 1200mg/m2/day x 2 days – total 2400mg/m2 over 46-48h - continuous infusion; repeat q2w to total of 6mo perioperative therapy)
- Xeloda 1250mg/m2 bd x 14 days q3w for total of 6 mo perioperative therapy
c. Concurrent chemoRT
- XRT + continuous infusion 5FU 225mg/m2 over 24h 7d/wk during XRT
- XRT + 5FU 400mg/m2 IV bolus + leucovorin 20mg/m2 iv bolus for 4d during wk 1 and wk 5 of XRT
- XRT for 5 wk + Xeloda 825mg/m2 bd 5 or 7d/wk
4. Surveillance
- follow-up q3-6mo x 2y then q6mo for total 5y
- CEA q3-6mo x 2y then q6mo for total of 5y for T2 or greater lesions
- Chest/abdominal/pelvic CT annually x 3y for patients at high risk of recurrence
- Colonoscopy in 1y except if no preoperative colonoscopy due to obstructive lesion, colonoscopy in 3-6 mo: if advanced adenoma repeat in 1y, if not repeat in 3y then q5y
- Proctoscopy q6mo x 5y for patients s/p LAR
- if CEA raised, colonoscopy, chest/abdominal/pelvic CT, PET scan
5. Advanced or metastatic disease
a. Initial: FOLFOX +/- bevacizumab or CapeOX +/- bevacizumab OR Folfox or CapeOX +/- cetuximab (KRAS wild-type gene only) OR FOLFIRI + bevacizumab OR FOLFIRI +/- cetuximab (KRAS wild type gene only) OR 5FU/leucovorin + bevacizumab OR FOLFOXIRI
b. Therapy after first progression: FOLFIRI/Irinotecan or FOLFIRI + cetuximab (KRAS WT gene) or Cetuximab (KRAS WT gene only) + Irinotecan OR FOLFOX or CapeOX or cetuximab (KRAS WT gene only) + Irinotecan, patients not able to tolerate combination, consider single angle cetuximab (KRAS WT gene) or panitumumab (KRAS WT gene) OR FOLFOX/CapeOX Irinotecan or Irinotecan/FOLFIRI
c. Cetuximab (KRAS WT gene) + Irinotecan or cetuximab (KRAS WT gene) or panitumumab (KRAS WT gene) OR FOLFOX/CapeOX
d. Patient not appropriate for intensive therapy: Capecitabine +/- bevacizumab or 5FU+leucovorin+/-bevacizumab or cetuximab (KRAS WT gene)
6. Chemotherapy regimens
a. FOLFOX 4
oxaliplatin 85mg/m2 iv over 2 hours D1
leucovorin 200m/m2 IV over 2 hours D1-2
followed on D1-2 by 5FU 400mg/m2 iv bolus then 600mg/m2 iv over 22 hours continuous infusion
repeat every 2 weeks
b. mFOLFOX 6
oxaliplatin 85mg/m2 iv over 2 hours D1
leucovorin 400mg/m2 iv over 2 hours D1
5FU 400mg/m2 iv bolus on D1 then 1200mg/m2/day x 2 days (total 2400mg/m2 over 46-48 hours) continuous infusion
repeat every 2 weeks
c. CapeOX
oxaliplatin 130mg/m2 D1
capecitabine 850-1000 mg/m2 bd for 14 days
repeat every 3 weeks
d. FOLFIRI
irinotecan 180mg/m2 iv over 30-120 minutes D1
leucovorin 400mg/m2 iv infusion to match duration of irinotecan infusion D1-2
followed on D1-2 followed on D1-2 by 5FU 400mg/m2 iv bolus then 600mg/m2 iv over 22 hours continuous infusion, repeat every 2 weeks
OR
irinotecan 180mg/m2 iv over 30-120 minutes D1
leucovorin 400mg/m2 iv infusion to match duration of irinotecan infusion D1
5FU 400mg/m2 iv bolus D1 then 1200mg/m2/day x 2 days (total 2400mg/m2 over 46-48 hours) continuous infusion
repeat every 2 weeks
Bevacizumab + 5FU containing regimens
bevacizumab 5mg/kg iv every 2 weeks + 5FU and leucovorin or FOLFOX or FOLFIRI
bevacizumab 7.5mg/kg iv every 3 weeks + CapeOX
e. Capecitabine
2000-2500 mg/m2/day PO in two divided doses, D1-14, followed by 7 days rest. Repeat every 3 weeks
f. Bolus or infusional 5FU/leucovorin
i. Roswell-Park regimen
Leucovorin 500mg/m2 iv over 2 hours, days 1/8/15/22/29/36
5FU 500 mg/m2 iv bolus 1 hour after start of leucovorin, days 1/8/15/22/29/36
Repeat every 8 weeks
ii. Biweekly
Leucovorin 400mg/m2 IV over 2 hours D1-2
5FU 400mg/m2 iv bolus, then 600mg/m2 iv over 22 hours continuous infusion, D1-2
Repeat every 2 weeks
iii. Simplified biweekly infusional 5FU/LV (sLV5FU2)
Leucovorin 400mg/m2 iv over 2 hours on D1,
Followed by 5FU bolus 400mg/m2 and then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) continuous infusion
Repeat every 2 weeks
iv. Weekly
Leucovorin 20mg/m2 as a 2h infusion
5FU 500mg/m2 bolus administered 1h after LV infusion
Repeat every week
5FU 2600 mg/m2 by 24h infusion plus leucovorin 500mg/m2
Repeat every week
g. FOLFOXIRI
Irinotecan 165 mg/m2 iv D1, oxaliplatin 85mg/m2 D1,
Leucovorin 400mg/m2 D1, fluorouracil 3200mg/m2 over 48h continuous infusion starting on D1
Repeat every 2 weeks
Irinotecan 125 mg/m2 IV over 30-90 minutes, D1/8/15/22. Repeat every 6 weeks.
Irinotecan 300-350mg/m2 IV over 30-90 minutes D1. Repeat every 3 weeks
Cetuximab (KRAS wild type gene only) +/- irinotecan
Cetuximab 400mg/m2 1st infusion then 250mg/m2 iv weekly or
Cetuximab 500mg/m2 iv every 2 weeks +/- irinotecan 300-350mg/m2 iv every 3 weeks or 180mg/m2 iv every 2 weeks or 125mg/m2 every week for 4 weeks
Every 6 weeks
Cetuximab (KRAS wild type gene only)
Cetuximab 400mg/m2 1st infusion, then 250mg/m2 iv weekly
Panitumumab (KRAS wild type gene only)
Panitumumab 6mg/kg iv over 60 minutes every 2 weeks
a. Colonoscopy
b. Rigid proctoscopy
c. Chest/abdominal/pelvic CT
d. CEA
e. EUS or endorectal or pelvic MRI
2. JH guidelines
a. ChemoRT
b. XELOX
c. XELIRI
3. Adjuvant therapy
a. Post-operative adjuvant chemotherapy for patients receiving preoprerative chemotherapy/RT
- 5FU 380mg/m2/day on days 1-5 +/- leucovorin iv 20mg/m2 on days 1-5 q28d x 4 cycles
- 5FU 500mg/m2 iv bolus injection 1h after the start of leucovorin infusion, once a wk for 6wk x 3 cycles, leucovorin 500mg/m2 iv over 2h once a wk for 6 weeks x 3 cycles (a cycle is comprised of 6wk followed by 2 wks of rest)
b. Post-operative adjuvant regimens for patients not receiving preoperative therapy
- 5FU + leucovorin x 1 cycle, then concurrent chemotherapy/XRT then 5FU/leucovorin x 2 cycles
(5FU 500mg/m2 iv bolus injection 1h after start of leucovorin infusion, once a wk for 6 wks + leucovorin 500mg/m2 IV over 2h once a wk for 6 wks. A cycle is 6 wks followed by 2 wks of rest)
- 5FU +/- leucovorin x 2 cycles then concurrent chemoRT then 5FU +/- leucovorin x 2 cycles (5FU 425mg/m2/day and leucovorin 20mg/m2/d, days 1-5 and 29-33 before RT. After RT the regimen is 5FU 380mg/m2/d and leucovorin 20mg/m2/day for 5 consecutive days x 2 cycles)
- FOLFOX
FOLFOX 4 (oxaliplatin 85mg/m2 IV over 2h D1, leucovorin 200mg/m2 IV over 2h D1&2, followed on D1 and 2 by 5FU 400mg/m2 iv bolus then 600mg/m2 iv over 22h continuous infusion; repeat q2w to total of 6 mo perioperative therapy)
mFOLFOX 6 (oxaliplatin 85mg/m2 IV over 2h D1 and leucovorin 400mg/m2 IV over 2h D1, 5FU 400mg/m2 IV bolus on D1 then 1200mg/m2/day x 2 days – total 2400mg/m2 over 46-48h - continuous infusion; repeat q2w to total of 6mo perioperative therapy)
- Xeloda 1250mg/m2 bd x 14 days q3w for total of 6 mo perioperative therapy
c. Concurrent chemoRT
- XRT + continuous infusion 5FU 225mg/m2 over 24h 7d/wk during XRT
- XRT + 5FU 400mg/m2 IV bolus + leucovorin 20mg/m2 iv bolus for 4d during wk 1 and wk 5 of XRT
- XRT for 5 wk + Xeloda 825mg/m2 bd 5 or 7d/wk
4. Surveillance
- follow-up q3-6mo x 2y then q6mo for total 5y
- CEA q3-6mo x 2y then q6mo for total of 5y for T2 or greater lesions
- Chest/abdominal/pelvic CT annually x 3y for patients at high risk of recurrence
- Colonoscopy in 1y except if no preoperative colonoscopy due to obstructive lesion, colonoscopy in 3-6 mo: if advanced adenoma repeat in 1y, if not repeat in 3y then q5y
- Proctoscopy q6mo x 5y for patients s/p LAR
- if CEA raised, colonoscopy, chest/abdominal/pelvic CT, PET scan
5. Advanced or metastatic disease
a. Initial: FOLFOX +/- bevacizumab or CapeOX +/- bevacizumab OR Folfox or CapeOX +/- cetuximab (KRAS wild-type gene only) OR FOLFIRI + bevacizumab OR FOLFIRI +/- cetuximab (KRAS wild type gene only) OR 5FU/leucovorin + bevacizumab OR FOLFOXIRI
b. Therapy after first progression: FOLFIRI/Irinotecan or FOLFIRI + cetuximab (KRAS WT gene) or Cetuximab (KRAS WT gene only) + Irinotecan OR FOLFOX or CapeOX or cetuximab (KRAS WT gene only) + Irinotecan, patients not able to tolerate combination, consider single angle cetuximab (KRAS WT gene) or panitumumab (KRAS WT gene) OR FOLFOX/CapeOX Irinotecan or Irinotecan/FOLFIRI
c. Cetuximab (KRAS WT gene) + Irinotecan or cetuximab (KRAS WT gene) or panitumumab (KRAS WT gene) OR FOLFOX/CapeOX
d. Patient not appropriate for intensive therapy: Capecitabine +/- bevacizumab or 5FU+leucovorin+/-bevacizumab or cetuximab (KRAS WT gene)
6. Chemotherapy regimens
a. FOLFOX 4
oxaliplatin 85mg/m2 iv over 2 hours D1
leucovorin 200m/m2 IV over 2 hours D1-2
followed on D1-2 by 5FU 400mg/m2 iv bolus then 600mg/m2 iv over 22 hours continuous infusion
repeat every 2 weeks
b. mFOLFOX 6
oxaliplatin 85mg/m2 iv over 2 hours D1
leucovorin 400mg/m2 iv over 2 hours D1
5FU 400mg/m2 iv bolus on D1 then 1200mg/m2/day x 2 days (total 2400mg/m2 over 46-48 hours) continuous infusion
repeat every 2 weeks
c. CapeOX
oxaliplatin 130mg/m2 D1
capecitabine 850-1000 mg/m2 bd for 14 days
repeat every 3 weeks
d. FOLFIRI
irinotecan 180mg/m2 iv over 30-120 minutes D1
leucovorin 400mg/m2 iv infusion to match duration of irinotecan infusion D1-2
followed on D1-2 followed on D1-2 by 5FU 400mg/m2 iv bolus then 600mg/m2 iv over 22 hours continuous infusion, repeat every 2 weeks
OR
irinotecan 180mg/m2 iv over 30-120 minutes D1
leucovorin 400mg/m2 iv infusion to match duration of irinotecan infusion D1
5FU 400mg/m2 iv bolus D1 then 1200mg/m2/day x 2 days (total 2400mg/m2 over 46-48 hours) continuous infusion
repeat every 2 weeks
Bevacizumab + 5FU containing regimens
bevacizumab 5mg/kg iv every 2 weeks + 5FU and leucovorin or FOLFOX or FOLFIRI
bevacizumab 7.5mg/kg iv every 3 weeks + CapeOX
e. Capecitabine
2000-2500 mg/m2/day PO in two divided doses, D1-14, followed by 7 days rest. Repeat every 3 weeks
f. Bolus or infusional 5FU/leucovorin
i. Roswell-Park regimen
Leucovorin 500mg/m2 iv over 2 hours, days 1/8/15/22/29/36
5FU 500 mg/m2 iv bolus 1 hour after start of leucovorin, days 1/8/15/22/29/36
Repeat every 8 weeks
ii. Biweekly
Leucovorin 400mg/m2 IV over 2 hours D1-2
5FU 400mg/m2 iv bolus, then 600mg/m2 iv over 22 hours continuous infusion, D1-2
Repeat every 2 weeks
iii. Simplified biweekly infusional 5FU/LV (sLV5FU2)
Leucovorin 400mg/m2 iv over 2 hours on D1,
Followed by 5FU bolus 400mg/m2 and then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) continuous infusion
Repeat every 2 weeks
iv. Weekly
Leucovorin 20mg/m2 as a 2h infusion
5FU 500mg/m2 bolus administered 1h after LV infusion
Repeat every week
5FU 2600 mg/m2 by 24h infusion plus leucovorin 500mg/m2
Repeat every week
g. FOLFOXIRI
Irinotecan 165 mg/m2 iv D1, oxaliplatin 85mg/m2 D1,
Leucovorin 400mg/m2 D1, fluorouracil 3200mg/m2 over 48h continuous infusion starting on D1
Repeat every 2 weeks
Irinotecan 125 mg/m2 IV over 30-90 minutes, D1/8/15/22. Repeat every 6 weeks.
Irinotecan 300-350mg/m2 IV over 30-90 minutes D1. Repeat every 3 weeks
Cetuximab (KRAS wild type gene only) +/- irinotecan
Cetuximab 400mg/m2 1st infusion then 250mg/m2 iv weekly or
Cetuximab 500mg/m2 iv every 2 weeks +/- irinotecan 300-350mg/m2 iv every 3 weeks or 180mg/m2 iv every 2 weeks or 125mg/m2 every week for 4 weeks
Every 6 weeks
Cetuximab (KRAS wild type gene only)
Cetuximab 400mg/m2 1st infusion, then 250mg/m2 iv weekly
Panitumumab (KRAS wild type gene only)
Panitumumab 6mg/kg iv over 60 minutes every 2 weeks
Gastric CA
1. Staging
- Abdominal CT with contrast
- CT/US pelvis (females)
- chest imaging
- OGD
- PET CT (optional)
- EUS (optional)
- H.pylori test
2. JH guidelines
a. primary chemoRT with weekly 5FU or ECF or XELOX
b. Metastatic
- first line: XELOX/5FU/CF
- second line: single agent TS-1 (for metastatic gastric CA)
- third line:
3. Net
a. Preoperative chemotherapy: ECF (epirubicin, cisplatin and 5FU) or modifications
b. Preoperative chemoradiation: paclitaxel or docetaxel plus 5FU/Xeloda
c. Postoperative chemoradiation: 5FU or Xeloda
d. Mets or locally advanced: DCF or modifications, ECF or modifications, Irinotectan plus cisplatin, oxaliplatin plus 5FU/Xeloda, paclitaxel based regimen
- Abdominal CT with contrast
- CT/US pelvis (females)
- chest imaging
- OGD
- PET CT (optional)
- EUS (optional)
- H.pylori test
2. JH guidelines
a. primary chemoRT with weekly 5FU or ECF or XELOX
b. Metastatic
- first line: XELOX/5FU/CF
- second line: single agent TS-1 (for metastatic gastric CA)
- third line:
3. Net
a. Preoperative chemotherapy: ECF (epirubicin, cisplatin and 5FU) or modifications
b. Preoperative chemoradiation: paclitaxel or docetaxel plus 5FU/Xeloda
c. Postoperative chemoradiation: 5FU or Xeloda
d. Mets or locally advanced: DCF or modifications, ECF or modifications, Irinotectan plus cisplatin, oxaliplatin plus 5FU/Xeloda, paclitaxel based regimen
Subscribe to:
Posts (Atom)
