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To date no effective salvage regimens have been reported for progressive or relapsed patients with advanced colorectal cancer, and new potentially active drugs or combinations should be evaluated for these situations. In vitro studies have suggested that lonidamine (LND) positively modulates the cytotoxic activity of mitomycin (MMC) in human colon cancer cell lines. From November 1993 to February 1995, 29 colorectal cancer patients previously treated with first line chemotherapy were admitted to the study. Treatment consisted of a combination of MMC at 12 mg/m2 administered intravenously on day 1, and LND at 150 mg per os three times daily for five consecutive days, starting two days before MMC; the treatment was repeated every four weeks for a total of 109 cycles. All patients were fully evaluable for response and toxicity. Two partial responses (7%), 10 stable disease, and 17 progressive disease were observed. Median survival duration was 212 days. Toxicity was mild, with no WHO grade 3-4 toxicity. MMC + LND combination therapy does not seem to be effective in previously treated advanced colorectal cancer patients.

Thirty-five patients affected by stage III-IV non-small-cell lung carcinomas were treated with ifosfamide 3 gr/m2 plus MESNA as uroprotector on day 1 and vinorelbine 25 mg/m2 i.v. bolus on day 1 and 8. This cycle was repeated every 21 days. Over a total of 35 evaluable patients, the overall response rate was 34% (95% CL 18-54%). One patient experienced a complete response with a duration of 7.2+ months, and 11 patients a partial response with a mean duration of 5.9+ months. Seven patients had no change and 16 improved. The overall survival was 7.6+ months. Over a total of 145 cycles, the most frequent toxicity was myelosuppression, but grade 3 leukopenia and grade 2 thrombocytopenia were seen only in 14% and 9% of cases, respectively. Only one patient suffered grade 4 leukopenia. Gastrointestinal toxicity was minimal; only five patients (14%) complained of grade 3 vomiting. This combination regimen can be safely given on an outpatient regimen, but it is relatively active in advanced non-small-cell lung cancer. However, it should be noted that >50% of the patients in this series had a performance status of <80 and >50% were older than 65 years.

To compare the efficacy of two biochemical modulations of 5-Fluorouracil in advanced colorectal cancer, 104 patients were randomized to receive high dose methotrexate followed by 5-Fluorouracil and leucovorin rescue on day 1 (Arm A) or folinic acid and 5-Fluorouracil on day 1 to 5 (Arm B). Both treatments were repeated every 3 weeks. In the 92 evaluable patients, objective responses were observed in 34% in Arm A and 31% in Arm B, with a median duration of 7.5 and 8.5 months, respectively. Median overall survival was similar in both groups (12 versus 13 months, respectively). A statistically significant difference was found only between responders and non responders of group B (p = 0.004). Toxicity was mild. In conclusion, no difference in therapeutic activity was seen between the two treatments and additional biochemical modulation must be evaluated.