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Colorectal Cancer

Colon Cancer
Adjuvant chemotherapy
Chemotherapy for stage IV (metastatic) cancer

Rectal Cancer
Neoadjuvant chemoradiation
Adjuvant chemoradiation

 

Colon Cancer

Adjuvant chemotherapy
     
5-FU + LV (Roswell park regimen)
5-FU 500 mg/m2 iv bolus 1 h after the start of leucovorin
Leucovorin 500 mg/m2 iv over 2 hrs
Qw x 6 wks every 8 wks for 3-4 cycles

Lembersky BC et al. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from national surgical adjuvant breast and bowel project protocol C-06. J Clin Oncol 2006; 24:2059 (link to the article). 

Haller, DG et al. Phase III study of fluorouracil, leucovorin and levamisole in high-risk stage II and III colon cancer: final report of intergroup 0089. J Clin Oncol 2005; 23:8671 (link to the article).

5-FU + LV (Mayo clinic regimen)
5-FU 370-425 mg/m2/d iv bolus d1-5
Leucovorin 20-25 mg/m2/d iv bolus d1-5
Q4w x 6 cycles

QUASAR Collaborative Group. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet 2007; 370:2020 (link to the article). 

Haller, DG et al. Phase III study of fluorouracil, leucovorin and levamisole in high-risk stage II and III colon cancer: final report of intergroup 0089. J Clin Oncol 2005; 23:8671 (link to the article).

O'Connell, MJ et al. Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol 1997; 15:246 (link to the article).

Uracil-Tegafur + Leucovorin
Uracil-Tegafur (UFT) 100 mg/m2 po every 8 hours x 4 weeks
Leucovorin (LV) 30 mg po every 8 hours x 4 weeks
Avoid food 1 hour before and 1 hour after each dose
Q5w x 5 cycles

Lembersky BC et al. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from national surgical adjuvant breast and bowel project protocol C-06. J Clin Oncol 2006; 24:2059 (link to the article).

Capecitabine
Capecitabine (Xeloda) 1250 mg/m2 po bid x 14 days
Q3w x 8 cycles

Twelves C et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005; 352:2696 (link to the article).

FOLFOX4
Leucovorin 200 mg/m2 iv over 2 hrs before 5-FU, d1 and 2
5-FU 400 mg/m2 iv bolus and then 600 mg/m2 iv over 22 hrs, d 1 and d2  
Oxaliplatin (Eloxatin) 85 mg/m2 iv d1
Q2w x 12 cycles

de Gramont A et al. Oxaliplatin/5FU/LV in adjuvant colon cancer: updated efficacy results of the MOSAIC trial, including survival, with a medium follow-up of six years. 2007 ASCO annual meeting. Abstract 4007 (link to the abstract). 

Goldberg RM et al. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administrated bimonthly in elderly patients with colorectal cancer. J Clin Oncol 2006; 24:4085 (link to the article).  

Andre, T et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004; 350:2343 (link to the article).

FOLFOX6
Leucovorin 400 mg/m2 iv over 2 hrs before 5-FU d1
5-FU 400 mg/m2 iv bolus d1 followed by 2400 mg/m2 iv over 46 hrs
Oxaliplatin (Eloxatin) 100 mg/m2 in 500 ml dextrose 5% iv over 2 hours d1
Q2w x 12 cycles

Tournigand, C et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. J Clin Oncol 2004; 22:229 (link to the article).

Modified FOLFOX6
Leucovorin 400 mg/m2 iv over 2 hrs before 5-FU d1
5-FU 400 mg/m2 iv bolus d1 followed by 2400 mg/m2 iv over 46 hrs
Oxaliplatin (Eloxatin) 85 mg/m2 iv d1
Q2w x 12 cycles

FLOX
5-FU 500 mg/m2 iv bolus 1 hr after start of leucovorin qw x 6 weeks every  8 weeks for 3 cycles
Leucovorin 500 mg/m2 iv over 2 hrs qw x 6 weeks every 8 weeks for 3 cycles
Oxaliplatin (Eloxatin) 85 mg/m2 iv over 2 hrs before 5-FU and Leucovorin week 1, 3, 5 of each 8-week cycle for 3 cycles

Wolmark N et al. A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon: survival results of NSABP protocol C-07. 2008 ASCO annual meeting. LBA4005 (link to the abstract). 

Kuebler JP et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol 2007; 25:2198 (link to the article). 

XELOX
Capecitabine (Xeloda) 1000 mg/m2 po bid x 14 days
Oxaliplatin (Eloxatin) 130 mg/m2 iv over 2 hrs d1
Q3w x 8 cycles

Schmoll H et al. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol 2007; 25:102 (link to the article). 

Chemotherapy for stage IV (metastatic) cancer   (back to top)

FOLFOX4
Leucovorin 200 mg/m2 iv over 2 hrs before 5-FU, d1 and 2
5-FU 400 mg/m2 iv bolus and then 600 mg/m2 iv over 22 hrs, d 1 and d2
Oxaliplatin (Eloxatin) 85 mg/m2 iv d1
Q2w 

Nordlinger B et al. Final results of the EORTC intergroup randomized phase III study 40983 (EPOC) evaluating the benefit of peri-operative FOLFOX4 chemotherapy for patients with potentially resectable colorectal cancer liver metastasis. 2007 ASCO annual meeting. LBA5 (link to the abstract). 

Goldberg RM et al. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administrated bimonthly in elderly patients with colorectal cancer. J Clin Oncol 2006; 24:4085 (link to the article). 

Goldberg RM et al. Randomized controlled trial of reduced-dose bolus fluorouracil plus leucovorin and irinotecan or infused fluorouracil plus leucovorin and oxaliplatin in patients with previously untreated metastatic colorectal cancer: A North American Intergroup Trial. J Clin Oncol 2006; 24:3347 (link to the article). 

Goldberg, RM et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004; 22:23 (link to the article).

Modified FOLFOX6
Leucovorin 350 mg/m2 iv over 2 hrs before 5-FU, d1
5-FU 400 mg/m2 iv bolus d1 followed by 2400 mg/m2 iv over 46 hrs
Oxaliplatin (Eloxatin) 85 mg/m2 iv d1
Q2w until progression or unacceptable toxicity

Hochster, HS et al. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol 2008; 26:3523 (link to the article).      

FUFOX
Oxaliplatin (Eloxatin) 50 mg/m2 iv over 2 hours followed by
Leucovorin 500 mg/m2 iv over 2 hours followed by
5-FU 2000 mg/m2 iv over 22 hours
D1, 8, 15 and 22
Q5w until progression or severe toxicity
After the 4th cycle, oxaliplatin is administrated only on d1 and 15

Porschen R et al. Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol 2007; 25:4217 (link to the article). 

FUOX
5-FU 2250 mg/m2 iv over  48 hours d1, 8, 15, 22, 29, 36
Oxaliplatin (Eloxatin) 85 mg/m2 iv over 2 hours d1, 15, 29
Q6w until progression or severe toxicity

Diaz-Rubio E et al. Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial. J Clin Oncol 2007; 25:4224 (link to the article).

Capecitabine + Oxaliplatin (CAPOX, XELOX)
Regimen 1
Capecitabine (Xeloda) 1000-850 mg/m2 po bid d1-14
Oxaliplatin (Eloxatin) 130 mg/m2 iv over 2 hours d1
Q3w until progression or severe toxicity

Cassidy J et al. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 2008; 26:2006 (link to the article).   

Diaz-Rubio E et al. Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial. J Clin Oncol 2007; 25:4224 (link to the article). 

Hochster, HS et al. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol 2008; 26:3523 (link to the article).       

Regimen 2
Capecitabine (Xeloda) 1000 mg/m2 po bid d1-14
Oxaliplatin (Eloxatin) 70 mg/m2 iv over 2 hours d1, 8
Q3w until progression or severe toxicity
After the 6th cycle, oxaliplatin is administrated only on d1

Mayer RJ et al. Should capecitabine replace infusional fluorouracil and leucovorin when combined with oxaliplatin in metastatic colorectal cancer (Editorial). J Clin Oncol 2007; 25:4165 (link to the editorial). 

Porschen R et al. Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol 2007; 25:4217 (link to the article).

Regimen 3
Capecitabine (Xeloda) 1750 mg/m2 po bid d1-7 and 14-21
Oxaliplatin (Eloxatin) 85 mg/m2 iv over 2 hours d1 and 14
Q4w 

Scheithauer W et al. Randomized multicenter phase II trial of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2003; 21:1307 (link to the article). 

FOLFIRI
Leucovorin 400 mg/m2 iv over 2 hrs before 5-FU d1
5-FU 400 mg/m2 iv bolus d1, and then 2400 mg/m2 iv over 46 hrs 
Irinotecan (Camptosar, CPT-11) 180 mg/m2 iv over 90 min d1
Q2w 

Fuchs CS et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropymidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C study. J Clin Oncol 2007; 25:4779 (link to the article).

Van Cutsem E et al. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial. 2007 ASCO annual meeting. Abstract 4000 (link to the abstract).

FOLFOXIRI
Irinotecan (Camptosar, CPT-11) 165 mg/m2 iv over 1 h d1
Oxaliplatin (Eloxatin) 85 mg/m2 iv over 2 hrs d1
Leucovorin 200 mg/m2 iv over 2 hrs d1
5-FU 3200 mg/m2 civi over 48 hrs d1-2
Q2w x 12 cycles

Falcone A et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: The Gruppo Oncologico Nord Ovest. J Clin Oncol 2007; 25:1670 (link to the article).

COI
Capecitabine (Xeloda) 1000 mg/m2 po bid d2-6
Oxaliplatin (Eloxatin) 85 mg/m2 iv d2
Irinotecan (Camptosar, CPT-11) 180 mg/m2 iv d1
Q2w

Bajetta E et al. Capecitabine plus oxaliplatin and irinotecan regimen every other week: a phase I/II study in first-line treatment of metastatic colorectal cancer. Ann Oncol 2007; 18:1810 (link to the article).  

FOLFOX4 + Bevacizumab
Leucovorin 200 mg/m2 iv over 2 hrs before 5-FU, d1 and 2
5-FU 400 mg/m2 iv bolus and then 600 mg/m2 iv over 22 hrs, d 1 and d2
Oxaliplatin (Eloxatin) 85 mg/m2 iv over 2 hrs d1
Bevacizumab (Avastin) 5-10 mg/kg iv over 30-90 min d1
Q2w 

Saltz LB et al. Bevacizumab (Bev) in combination with XELOX or FOLFOX4: efficacy results from XELOX-1/No 16966, a randomized phase III trial in the first-line treatment of metastatic colorectal cancer (MCRC). 2007 Gastrointestinal Cancers Symposium. Abstract 238 (link to the abstract).     

Giantonio, BJ et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007; 25:1539 (link to the article).

FOLFOX4 + Cetuximab (for patients with wild-type KRAS)
Leucovorin 200 mg/m2 iv over 2 hrs before 5-FU, d1 and 2 q2w
5-FU 400 mg/m2 iv bolus and then 600 mg/m2 iv over 22 hrs, d 1 and d2 q2w
Oxaliplatin (Eloxatin) 85 mg/m2 iv over 2 hrs d1q2w
Cetuximab (Erbitux) 400 mg/m2 iv loading over 2 hours d1, and then 250 mg/m2 iv over 1 hour qw
Until progression

Bokemeyer C et al. KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: the OPUS experience. 2008 ASCO annual meeting. Abstract 4000 (link to the abstract). 

Tabernero J et al. Phase II trial of cetuximab in combination with fluorouracil, leucovorin, and oxaliplatin in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 2007; 25:5225 (link to the article). 

Bokemeyer C et al. Cetuximab plus 5-FU/FA/Oxaliplatin (FOLFOX-4) versus FOLFOX-4 in the first-line treatment of metastatic colorectal cancer (mCRC): OPUS, a randomized phase II study. 2007 ASCO annual meeting. Abstract 4035 (link to the abstract).

FOLFOX6 + Bevacizumab
Leucovorin 400 mg/m2 iv over 2 hrs before 5-FU d1
5-FU 400 mg/m2 iv bolus d1 followed by 2400 mg/m2 iv over 46 hrs
Oxaliplatin (Eloxatin) 100 mg/m2 iv d1
Bevacizumab (Avastin) 5 mg/kg iv d1
Q2w 

Modified FOLFOX6 + Bevacizumab
Leucovorin 350 mg/m2 iv over 2 hrs before 5-FU, d1
5-FU 400 mg/m2 iv bolus d1 followed by 2400 mg/m2 iv over 46 hrs
Oxaliplatin (Eloxatin) 85 mg/m2 iv d1
Bevacizumab (Avastin) 5 mg/kg iv d1
Q2w until progression or unacceptable toxicity

Hochster, HS et al. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol 2008; 26:3523 (link to the article).       

Modified FOLFOX7 with intermittent Oxaliplatin + Bevacizumab
Leucovorin 200 mg/m2 iv d1
5-FU 2400 mg/m2 iv over 46 hrs
Oxaliplatin (Eloxatin) 85 mg/m2 iv d1
Bevacizumab (Avastin) 5 mg/kg iv d1
Q2w x 8 cycles
Alternating with
Leucovorin 200 mg/m2 iv d1
5-FU 2400 mg/m2 iv over 46 hrs
Bevacizumab (Avastin) 5 mg/kg iv d1
Q2w x 8 cycles

Grothey A et al. Intermittent oxaliplatin (Oxali) administration and time-to-treatment-failure (TTF) in metastatic colorectal cancer (mCRC): final results of the phase III CONcePT trial. 2008 ASCO annual meeting. Abstract 4010 (link to the abstract).  

IFL + Bevacizumab
Leucovorin 20 mg/m2 iv bolus qw x 4 wks every 6 wks
5-FU 500 mg/m2 iv bolus qw x 4 wks every 6 wks
Irinotecan (Camptosar, CPT-11) 125 mg/m2 iv qw x 4 wks every 6 wks
Bevacizumab (Avastin) 5 mg/kg iv q2w

Hurwitz, H et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350:2335 (link to the article).

LV + 5-FU + Irinotecan + Bevacizumab
Leucovorin 200 mg/m2 iv over 2 hrs before 5-FU, d1 and 2
5-FU 400 mg/m2 iv bolus and then 600 mg/m2 iv over 22 hrs, d1 and 2   
Irinotecan (Camptosar, CPT-11) 180 mg/m2 iv d1
Bevacizumab (Avastin) 5 mg/kg iv d1
Q2w 

FOLFIRI  + Bevacizumab
Leucovorin 400 mg/m2 iv over 2 hrs before 5-FU d1
5-FU 400 mg/m2 iv bolus d1, and then 2400 mg/m2 iv over 46 hrs 
Irinotecan (Camptosar, CPT-11) 180 mg/m2 iv over 90 min d1
Bevacizumab (Avastin) 5 mg/kg iv d1
Q2w 

Fuchs CS et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropymidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C study. J Clin Oncol 2007; 25:4779 (link to the article). 

FOLFIRI + Cetuximab (for patients with wild-type KRAS)
Leucovorin 400 mg/m2 iv over 2 hrs before 5-FU d1 q2w
5-FU 400 mg/m2 iv bolus d1, and then 2400 mg/m2 iv over 46 hrs q2w
Irinotecan (Camptosar, CPT-11) 180 mg/m2 iv d1 q2w
Cetuximab (Erbitux) 400 mg/m2 iv loading d1, and then 250 mg/m2 iv qw 

Van Cutsem E et al. KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with or without cetuximab: the CRYSTAL experience. 2008 ASCO annual meeting. Abstract 2 (link to the abstract). 

Van Cutsem E et al. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial. 2007 ASCO annual meeting. Abstract 4000 (link to the abstract). 

XELIRI  + Bevacizumab
Capecitabine (Xeloda) 1000 mg/m2 (750 mg/m2 for pts > 65) po bid x 14 days q3w
Irinotecan (Camptosar, CPT-11) 250 mg/m2 (200 mg/m2 for pts > 65) iv d1 q3w
Bevacizumab (Avastin) 7.5 mg/kg iv d1 q3w 

Patt, YZ et al. Capicitabine plus irinotecan as first-line treatment for metastatic colorectal cancer: Final safety findings from a phase II trial (abstract). 2004 ASCO annual meeting. Abstract 3602 (link to the abstract).    

CapIri
Capecitabine (Xeloda) 1000 mg/m2 po bid x 14 days
Irinotecan (Camptosar, CPT-11) 100 mg/m2 iv d1, 8
Q22d

Grothey A, et al. Capecitabine/irinotecan (CapIri) and capecitabine/oxaliplatin (CapOx) are active second-line protocols in patients with avdanced colorectal cancer (ACRC) after failure of first-line combination therapy: results of a randomized phase II study. 2004 ASCO annual meeting. Abstract 3534 (link to the abstract).

XELOX + Bevacizumab
Oxaliplatin (Eloxatin) 130 mg/m2 iv over 2 hours d1
Capecitabine (Xeloda) 1000-850 mg/m2 po bid d1-14
Bevacizumab (Avastin) 7.5 mg/kg iv over 30-90 min d1
Q3w until progression or unacceptable toxicity

Punt CJ et al. Randomized phase III study of capecitabine, oxaliplatin, and bevacizumab with or without cetuximab in advanced colorectal cancer (ACC), the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). 2008 ASCO annual meeting. LBA4011. (link to the abstract).  

Saltz LB et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study. J Clin Oncol 2008; 26:2013 (link to the article).    

Hochster, HS et al. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol 2008; 26:3523 (link to the article).              

5-FU + LV + Bevacizumab (Roswell park regimen)
5-FU 500 mg/m2 iv bolus qw x 6 wks every 8 wks x 6 cycles
Leucovorin 500 mg/m2 iv over 2 hrs qw x 6 wks every 8 wks x 6 cycles
Bevacizumab (Avastin) 5 mg/kg iv over 30-90 min q2w x 48 weeks

Kabbinavar, F et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003; 21:60 (link to the article).             

5-FU + LV + Bevacizumab (Mayo clinic regimen)
5-FU 425 mg/m2/d iv bolus d1-5 q4w
Leucovorin 20 mg/m2/d iv bolus d1-5 q4w
Bevacizumab (Avastin) 5 mg/kg iv q2w          

Capecitabine
Capecitabine (Xeloda) 1000-1250 mg/m2 po bid x 14 days q3w till disease progression

Van Cutsem, E et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: Results of a large phase III study. J Clin Oncol 2001; 19:4097 (link to the article).

Hoff, PM et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 2001; 19:2282 (link to the article).

Uracil-Tegafur + Leucovorin
Uracil-Tegafur (UFT) 100 mg/m2 po every 8 hours x 4 weeks
Leucovorin (LV) 30 mg po every 8 hours x 4 weeks
Avoid food 1 hour before and 1 hour after each dose
Q5w until disease progression or unacceptable toxicity

Hochster HS et al. Phase II study of uracil-tegafur with leucovorin in elderly (> 75 years old) patients with colorectal cancer: ECOG 1299. J Clin Oncol 2007; 25:5397 (link to the article). 

Irinotecan
Irenotecan (Camptosar, CPT-11)
Regimen 1 (qw)
125 mg/m2 iv qw

Regimen 2 (q3w)
350 mg/m2, or 300 mg/m2 if > 70 years of age, ECOG performance status 2 or prior pelvic radiation, iv q3w

Fuchs CS et al. Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol 2003; 21:807 (link to the article). 

Cetuximab (for patients with wild-type KRAS)
Cetuximab (Erbitux) 400 mg/m2 iv loading, then 250 mg/m2 iv qw till disease progression
Premedication Diphenhydramine (Benadryl) 50 mg iv 30-60 min before cetuximab

Approved by FDA on 10/2/07 (link to FDA file). 

Jonker DJ et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007; 357-2040 (link to the article). 

Lenz HJ et al. Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol 2006; 24:4914 (link to the article). 

Cunningham, D et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351:337 (link to the article).

Cetuximab + Irinotecan (for patients with wild-type KRAS)
Cetuximab (Erbitux) 400 mg/m2 iv loading over 2 hours, then 250 mg/m2 iv over 1 hour qw
Irinotecan (Camptosar, CPT-11) 350 mg/m2 iv over 90 min q3w or 180 mg/m2 iv q2w or 125 mg/m2 iv qw x 4 wks every 6 wks
Continue treatment until disease progression or unacceptable toxicity

Sobrero AF et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26:2311(link to the article).  

Cunningham, D et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351:337 (link to the article).

CBI (for patients with wild-type KRAS)
Cetuximab (Erbitux) 400 mg/m2 iv loading over 2 hours, then 250 mg/m2 iv qw
Bevacizumab (Avastin) 5 mg/kg iv q2w
Irinotecan (Camptosar, CPT-11) 350 mg/m2 iv q3w or 180 mg/m2 iv q2w or 125 mg/m2 iv qw x 4 wks every 6 wks

Saltz LB et al. Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J Clin Oncol 2007; 25:4557 (link to the article).

CB (for patients with wild-type KRAS)
Cetuximab (Erbitux) 400 mg/m2 iv loading over 2 hours, then 250 mg/m2 iv qw
Bevacizumab (Avastin) 5 mg/kg iv q2w

Saltz LB et al. Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J Clin Oncol 2007; 25:4557 (link to the article).

Panitumumab
Panitumumab (Vectibix) 6 mg/kg iv over 60 min q2w

FDA approved on 9/27/06 (link to FDA file).

Cutsem EV et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 2007; 25:1658 (link to the article).

 

Rectal Cancer (back to top)

Neoadjuvant chemoradiation

5-FU + RT
5-FU 1000 mg/m2/d civi x 5 days during the first and fifth weeks of radiotherapy
Concurrent radiotherapy 50.4 Gy
Surgery in 4-6 weeks
5-FU 500 mg/m2/d civi d1-5 q4w x 4 cycles

Sauer, R et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351:1731 (link to the article).

5-FU + LV + RT
5-FU 350 mg/m2 /d iv over 20 min d1-5 during the first and fifth weeks of radiotherapy
Leucovorin 20 mg/m2/d iv d1-5 during the first and fifth weeks of radiotherapy
Concurrent radiotherapy 45 Gy in 25 fractions of 1.8 Gy over 5 weeks
Surgery in 3-10 weeks
3-10 weeks after surgery:
5-FU 350 mg/m2/d iv d1-5 q3w x 4 cycles
Leucovorin 20 mg/m2/d iv d1-5 q3w x 4 cycles

Collette L et al. Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? a trial of the European Organization for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol 2007; 25:4379 (link to the article).

Minsky BD et al. Adjuvant management of rectal cancer: the more we learn, the less we know (Editorial). J Clin Oncol 2007; 25:4339 (link to the editorial).   

Bosset JF et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Eng J Med 2006; 355:1114 (link to the article).

Gerard J et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 2006; 24:4602 (link to the article).  

Capecitabine + RT
Regimen 1
Capecitabine (Xeloda ) 825 mg/m2 po bid x 7 days/week
Concurrent radiotherapy 50-52.5 Gy
Surgery 4-8 weeks later
Adjuvant capecitabine 1250 mg/m2 po bid x 14 days q3w for 4 cycles

Krishnan S et al. Phase II study of capecitabine (Xeloda) and concurrent boost radiotherapy in patients with locally advanced rectal cancer. Int J Radiat Oncol Bio Phy 2006; 66:762 (link to the article). 

Kim JC et al. Preoperative concurrent radiotherapy with capecitabine before total mesorectal excision in locally advanced rectal cancer. Int J Radiat Oncol Bio Phy 2006; 63:346 (link to the article). 

De Paoli A et al. Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study. Ann Oncol 2006; 17:246 (link to the article). 

Regimen 2
Capecitabine (Xeloda) 900 mg/m2 po bid x 5 days/week 
Concurrent radiotherapy 1.8 Gy/d to a total of 45 Gy
Surgery 4-6 weeks later

Craven I et al. Preoperative radiotherapy combined with 5 days per week capecitabine chemotherapy in locally advanced rectal cancer. Br J Cancer 2007; 97:1333 (link to the article). 

XELOX + RT
Regimen 1
Capecitabine (Xeloda) 825 mg/m2 po bid d1-14 and 22-35
Oxaliplatin (Eloxatin) 50 mg/m2 iv over 2 hrs d1, 8, 22, 29
Concurrent radiotherapy 1.8 Gy/d to a total of 50.4 Gy
Surgery 4-6 weeks later
4-6 weeks after surgery:
Capecitabine (Xeloda) 1000 mg/m2 po bid d1-14
Oxaliplatin (Eloxatin) 130 mg/m2 iv d1
Q3w x 4 cycles

Rodel C et al. Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. J Clin Oncol 2007; 25:110 (link to the article). 

Rodel C et al. Phase I/II trial of capecitabine, oxaliplatin, and radiation for rectal cancer. J Clin Oncol 2003; 21:3098 (link to the article). 

Regimen 2
Capecitabine (Xeloda) 825 mg/m2 po bid on each day of radiation
Oxaliplatin (Eloxatin) 50 mg/m2 iv over 2 hrs qw x 5 weeks
Concurrent radiotherapy 1.8 Gy/d to a total of 45 Gy over 5 weeks
Surgery 6-8 weeks later
Adjuvant 5-FU and leucovorin recommended if positive lymph node at surgery

Machiels JP et al. Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer: the RadiOxCape study. Ann Oncol 2005; 16:1898 (link to the article).

5-FU + Oxaliplatin + RT
5-FU 200 mg/m2/d civi throughout radiotherapy
Oxaliplatin (Eloxatin) 60 mg/m2 iv over 1 hour qw
Concurrent radiotherapy 1.8 Gy/d to a total of 45 Gy over 5 weeks
Surgery 4-6 weeks later
Adjuvant 5-FU and leucovorin recommended

Ryan DP et al. Phase I/II study of preoperative oxaliplatin, fluorouracil, and external-beam radiation therapy in patients with locally advanced rectal cancer: Cancer and Leukemia Group B 89901. J Clin Oncol 2006; 24:2557 (link to the article).  

Aschele C et al. A phase I-II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer. Ann Oncol 2005; 16:1140 (link to the article).  

Adjuvant chemoradiation  (back to top)

5-FU + RT
Regimen 1
4-6 weeks after surgery
5-FU 500 mg/m2/d iv bolus d1-5 and d36-40
Beginning on day 64, concurrent radiotherapy 45 Gy and 5-FU 225 mg/m2/d civi throughout radiotherapy
5-FU 450 mg/m2/d iv bolus d134 to 138 and d169 to 173

O'Connell, MJ et al. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 1994; 331:502 (link to the article).

Regimen 2
20-70 days after surgery
5-FU 500 mg/m2/d iv bolus d1-5 and d29-33
Beginning on day 57, concurrent radiotherapy 45 Gy and 5-FU 225 mg/m2/d civi throughout radiotherapy
28 days after completion of chemoradiaton, 5-FU 450 mg/m2/d iv bolus d1-5 q4w x 2 cycles

Smalley SR et al. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol 2006; 24:3542 (link to the article).  

Regimen 3
20-70 days after surgery
5-FU 300 mg/m2/d civi d1-42
2 weeks later, concurrent radiotherapy 45 Gy and 5-FU 225 mg/m2/d civi throughout radiotherapy, starting on day 57
28 days after completion of chemoradiaton, 5-FU 300 mg/m2/d civi for 56 days

Smalley SR et al. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol 2006; 24:3542 (link to the article).