Search

Radical radiation therapy (5000 rads in 20 fractions in 4 weeks) combined with iv mitomycin (10 mg/m2) and 5-FU (1000 mg/m2/24 hours for 4 days) was used to treat 13 patients with locally advanced but operable squamous cell carcinoma of the anal canal. All patients achieved local control and retained anal continence, and none developed metastases. The patients were followed from 4 to 34 months (median, 12). Severe acute gastrointestinal toxic effects were seen in three patients; the same patients had significant thrombocytopenia or leukopenia. Treatment with this combined program may allow conservative management of squamous cell carcinoma of the anal canal and should be considered as an alternative to abdominoperineal resection.

We determined the steady-state plasma levels of 5-FU when the drug was administered by continuous infusion for 5 days during 21 courses in patients with metastatic colorectal carcinoma receiving concomitant oral allopurinol given at a dose of 300 mg orally three times/day. The steady-state plasma level increased from 3.37 to 7.49 microM with dose increases from 1.25 to 2.25 g/m2/day. Clearance ranged from 1.79 to 2.41 L/min/m2. Although we observed a large day-to-day variation and a large patient-to-patient variation in plasma 5-FU levels at any given dose level, these were not significant. The plasma level of 5-FU increased linearly with dose. The difference between 5-FU plasma levels with dose was significant (P = 0.002). When the levels were adjusted for patient-to-patient and day-to-day variation the difference remained significant (P = 0.02). The results indicate that: (a) plasma levels of 5-FU may show large but insignificant variation from patient to patient and from day to day; and (b) steady-state plasma levels and 5-FU increased linearly with dose.

Thirty patients with advanced gastric carcinoma were treated with doxorubicin combined with mitomycin; only four (13%) responded. Myelosuppression was the major toxic effect; there was one toxic death. The overall median survival was 14 weeks (range, 2-42), which is no different from that reported for untreated patients. The combination of doxorubicin and mitomycin alone cannot be recommended for use in patients with advanced gastric carcinoma.

The National Cancer Institute of Canada Clinical Trials Group conducted a phase II study of carboplatin (400 mg/m2) given as an iv bolus every 4 weeks in patients with measurable advanced ovarian cancer who had failed or relapsed following standard platinum-containing therapy. Four complete and eight partial responses were seen in 43 evaluable patients. Toxicity was primarily hematologic. Myelosuppression, particularly thrombocytopenia, was severe in one-third of patients treated at the 400-mg/m2 starting dose. Carboplatin has antitumor activity in this clinical setting, but a lower starting dose is recommended.