First-line combination chemotherapy with mitoxantrone, methotrexate, vincristine and carboplatin (MIMOC) in advanced breast cancer.

51 patients with stage IIIB and IV breast cancer entered a prospective phase II study of combination chemotherapy that consisted of mitoxantrone (8 mg/m2) day 1, methotrexate (25 mg/m2) day 1, vincristine (1 mg/m2) day 2 and carboplatin (250 mg/m2) day 2 (MIMOC) given in a 3-weekly schedule. None had received prior chemotherapy for metastatic disease, although 16 patients were given adjuvant chemotherapy. Objective response to treatment was seen in 29 of 48 patients analysed for response (60%) with 8 complete responses (CR). 7 out of 8 patients with stage IIIB disease responded, 2 of them completely. Responses were seen in all sites but the best results were achieved in lung metastases with 50% CR. The median duration of response was 8 months and the median time to disease progression was 12 months. The main toxicity was nausea and vomiting which was severe in 20% of the patients. Other toxicities were mild. MIMOC was administered on an out-patient basis and appears to be effective as first-line treatment in advanced breast cancer.

Concomitant administration of 4-hydroxypyrazolopyrimidine (allopurinol) and high-dose continuous infusion 5-fluorouracil.

We tried to study the protection of allopurinol (HPP) from the toxicity of 5-fluorouracil (5-FU). A total of 29 patients received 74 cycles of chemotherapy (16 colon adenocarcinomas, 7 head and neck, 3 breast cancers and 3 cancers of pancreas). HPP was given 900 mg/day p.o. 4 days prior to treatment, and continued with same dose throughout the course of 5-FU and for 12 days after completion of the treatment. 5-FU was administered in 24 hour intravenous infusions on days 1-5 (dose range 900-1,200 mg/m2/day). 5-FU was given alone or in combination with mitomycin-C 10 mg/m2/day (1st day), epirubicin 40 mg/m2/day (1st, 2nd day), cis-platinum 120 mg/m2/day (1st day). In comparison with other studies the toxicity was limited. We conclude that HPP can diminish the side effects, especially myelosuppression, allowing an increase in the maximum tolerated dose of 5-FU; even if combined with other cytostatic drugs. Control studies must be done to confirm our observations.

Folinic acid plus high-dose 5-fluorouracil with allopurinol protection in the treatment of advanced colorectal carcinoma.

Protection by prolonged administration of allopurinol against high-dose 5-fluorouracil (5-FU) administered with folinic acid in 74 patients with colorectal cancer was investigated. The dose of 5-FU was 700 mg/m2 per day for 5 days. Of 41 patients without previous chemotherapy, 1 had a complete response and 4 had partial responses (total 12%), 15 remained stable and 21 progressed. Mean duration of response was 7.4 (1.8-12.6) months. The most frequent toxicities were decreased granulocytes (13%), diarrhoea (37%), and stomatitis (35%), which were similar to the frequencies of other studies with lower doses of 5-FU without allopurinol. Prolonged administration of allopurinol thus gives some protection to patients with colorectal cancer who receive folinic acid plus high-dose 5-FU but responses were not better than those with conventional doses.