Sequential phase II studies of chemotherapy for colorectal cancer with 5-fluorouracil and vindesine with or without methyl-1,3 cis(2 chloroethyl)-1-nitrosourea.
Vindesine, a newer vinca alkaloid, has been demonstrated to have activity against colorectal cancer during phase I studies. This report describes the results of two phase II trials in which vindesine was administered with 5-fluorouracil (5-FU) or in combination with 5-FU and methyl-1,3 cis(2 chloroethyl)-1-nitrosourea (MeCCNU). One of 16 patients (6%) given 5-FU-vindesine, and 4 of 31 (13%) patients in the 5-FU-vindesine-MeCCNU group achieved partial response (PR). Stable disease was observed in 50% of the 5-FU vindesine and 48% of the 5-FU-vindesine-MeCCNU group. In each treatment group, survival of respondents and those with stable disease was statistically superior (p less than 0.02) to that of those with progressive disease; there was no difference however, in overall survival between the two treatment groups and no enhancement of survival compared to published reports of results with 5-FU alone. No chemotherapy-related deaths occurred and both treatment regimens were well tolerated. Myelosuppression, which occurred with equal (50%) frequency in both regimens, was the major dose-limiting toxicity. MeCCNU increased the incidence of gastrointestinal toxicity. Vindesine neurotoxicity occurred in approximately 4% of the evaluable courses in each group. Combination therapy with 5-FU vindesine with or without MeCCNU in the dosages administered did not significantly increase the activity of 5-FU. Further evaluation of vindesine will require dosage modification.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009607:Nitrosourea Compounds / Q000008:administration & dosage*; D010976:Platelet Count; D011379:Prognosis; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D012673:Semustine / Q000008:administration & dosage* / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014751:Vindesine
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D012673:Semustine; D014747:Vinblastine; D014751:Vindesine; D005472:Fluorouracil