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