Colorectal cancer - historical

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main colorectal cancer page for current regimens.

5 regimens on this page 5 variants on this page

Metastatic disease, first-line

Fluorouracil & Methotrexate (MF)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Wils et al. 2003	1992-1994	Phase 3 (C)	MF & PALA	Did not meet endpoints of RR/PFS/OS

Chemotherapy

• Fluorouracil (5-FU)
• Methotrexate (MTX)

References

1. Wils J, Blijham GH, Wagener T, De Greve J, Jansen RL, Kok TC, Nortier JW, Bleiberg H, Couvreur ML, Genicot B, Baron B; EORTC Gastrointestinal Group. High-dose 5-fluorouracil plus low dose methotrexate plus or minus low-dose PALA in advanced colorectal cancer: a randomised phase II-III trial of the EORTC Gastrointestinal Group. Eur J Cancer. 2003 Feb;39(3):346-52. link to original article PubMed

Fluorouracil & Mitomycin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Price et al. 2004	1996-1998	Phase 3 (C)	Fluorouracil & Mitomycin; chronomodulated	Did not meet endpoints of FFS/OS

Chemotherapy

• Fluorouracil (5-FU)
• Mitomycin (Mutamycin)

References

1. Price TJ, Ross PJ, Hickish T, Tait D, Norman AR, Ford HE, Middleton G, Sumpter K, Hill M, Oates J, Cunningham D. Phase III study of mitomycin-C with protracted venous infusion or circadian-timed infusion of 5-fluorouracil in advanced colorectal carcinoma. Clin Colorectal Cancer. 2004 Feb;3(4):235-42. link to original article PubMed

Fluorouracil & Semustine

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Baker et al. 1976	1973-1974	Phase 3 (C)	5-FU	Superior ORR
Engstrom et al. 1982 (ECOG E4275)	NR	Phase 3 (E-switch-ic)	1. 5-FU, Semustine, Vincristine 2. 5-FU, Dacarbazine, Semustine 3. 5-FU, Dacarbazine, Semustine, Vincristine 4. 5-FU & Hydrea	Did not meet endpoints of RR/OS

Chemotherapy

• Fluorouracil (5-FU)
• Semustine (MeCCNU)

References

1. Baker LH, Talley RW, Matter R, Lehane DE, Ruffner BW, Jones SE, Morrison FS, Stephens RL, Gehan EA, Vaitkevicius VK; Southwest Oncology Group. Phase III comparison of the treatment of advanced gastrointestinal cancer with bolus weekly 5-FU vs methyl-CCNU plus bolus weekly 5-FU: a Southwest Oncology Group study. Cancer. 1976 Jul;38(1):1-7. link to original article PubMed
2. ECOG E4275: Engstrom PF, MacIntyre JM, Douglass HO Jr, Muggia F, Mittelman A. Combination chemotherapy of advanced colorectal cancer utilizing 5-fluorouracil, semustine, dacarbazine, vincristine, and hydroxyurea: a phase III trial by the Eastern Cooperative Oncology Group (EST: 4275). Cancer. 1982 Apr 15;49(8):1555-60. link to original article PubMed

FOLFOX chronotherapy

FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Lévi et al. 1997	1991-1993	Phase 3 (E-switch-ic)	FOLFOX; CI	Superior TTF

Note: This schedule is "chronomodulated"; see paper for details.

Chemotherapy

• Folinic acid (Leucovorin) 300 mg/m² IV over 12 hours once per day on days 1 to 5, given second, with 5-FU
• Fluorouracil (5-FU) 600 mg/m² IV over 12 hours once per day on days 1 to 5, given second, with leucovorin
• Oxaliplatin (Eloxatin) 20 mg/m² IV over 12 hours once per day on days 1 to 5, given first

21-day cycles

References

1. Lévi F, Zidani R, Misset JL; International Organization for Cancer Chronotherapy. Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. Lancet. 1997 Sep 6;350(9079):681-6. link to original article contains dosing details in manuscript PubMed