In a prospective phase III multicenter trial, 213 patients with advanced measurable or nonmeasurable gastric cancer were randomized to receive methotrexate (MTX), fluorouracil (5-FU), and Adriamycin (doxorubicin; Farmitalia Carlo Erba, Milan, Italy) (FAMTX) or 5-FU, Adriamycin, and mitomycin (FAM). The results show a significantly superior response rate (41% v 9% [P less than .0001]), and survival (median, 42 weeks v 29 weeks [P = .004]) for FAMTX. There was a cumulative thrombocytopenia in FAM and not in FAMTX. The FAMTX protocol should be the reference treatment in future clinical trials that seek to improve the therapeutic outcome in advanced gastric cancer.

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The authors studied the alkylating activity in the blood serum of man and rats after administration of cyclophosphamide, and its dependence on dosage. The alkylating activity was determined by means of the NBP test. For the process of activation, distribution in the body, and elimination, a mathematic model was developed and checked by means of the experimental data. The following results were obtained: 1. The cyclophosphamide activation curves studied for the doses of 15.6, 31.3, and 62.5 mg/kg are very constant in the rat, the NBP regression lines depending clearly on dosage. 2. The pharmacokietics of the metabolite level in man, studied for the doses of 30 and 60 mg/kg, show great individual fluctuations. But even here the dependence of the activity curves on dosage is statistically significant. 3. The average peaks of the metabolite level in man, related to the same dose, are about half to three quarters those found in the rat. 4. In man, the alkylating activity in the blood is detectable longer than in the rat. The values of the elimination constants in man are about two thirds of those in the rat. 5. Direct determination of the cyclophosphamide activation rate in liver sections of man and rats shows the activation rate in man related to the moist weight of the liver, to be‐even in vitro‐only about 60% of that of the rat. 6. Our findings show that there are no basic qualitative differences in cyclophosphamide activation between man and rat. They offer interesting aspects for the improvement of the therapeutic use of cyclophosphamide.

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This report describes some experimental and clinical studies showing the following: (1) in animals under protection of mesna the dose of ifosfamide (Ifo) can be increased significantly; (2) fractionated administration of Ifo, cyclophosphamide (CPA), or the stabilized metabolite of cyclophosphamide (ASTA Z 7557) is less toxic than single push‐injection of the same total daily dose and therapeutically more effective; and (3) in humans under the protection of mesna the continuous infusions of ifosfamide over 5 days leads to an increase of the MTD compared with single daily short‐term infusion and responses in some solid tumors, e.g., soft tissue sarcomas.