Phase II study of intravenous CI-958 in metastatic colorectal adenocarcinoma.

In a multicenter, phase II trial, CI-958, a benzothiopyranoindazole DNA intercalator, was administered to 18 patients who had not received prior chemotherapy for metastatic colorectal cancer. The drug was given by intravenous infusion at a dose of 700 mg/m2 every 21 days. There were no objective responses. Grades III and IV toxic effects were limited to granulocytopenia in 42% of courses and anemia in 5% of courses. There was one case of grade III increase in transaminases. Our results show that at this dose and schedule, CI-958 lacks activity against colorectal cancer.

Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma.

BACKGROUND: Adjuvant chemotherapy is widely used for breast cancer and is known to extend survival. Some clinicians seek a greater survival benefit by increasing the intensity of the dose, whereas others lower it to diminish toxicity. METHODS: The Cancer and Leukemia Group B (CALGB) conducted a randomized trial of different levels of doses and dose intensity (dose per unit of time) of adjuvant chemotherapy in 1572 women with node-positive, stage II breast cancer who were assigned to three treatment groups. One group received 400 mg of cyclophosphamide per square meter of body-surface area and 40 mg of doxorubicin per square meter once every 28 days and 400 mg of fluorouracil per square meter twice every 28 days, for six cycles. Another group received 50 percent higher doses of the three drugs (600 mg, 60 mg, and 600 mg, respectively) but for only four cycles, so that the total dose was identical in these two groups but the dose intensity was higher in the first. The third group of women received half the total dose used in the other two groups and at half the dose intensity used in the second group. RESULTS: After a median of 3.4 years of follow-up, the women treated with a high or moderate dose intensity had significantly longer disease-free survival (P < 0.001) and overall survival (P = 0.004) than those treated with a low dose intensity, in three-way log-rank comparisons. However, the difference in survival between the two groups treated with a moderate or high dose intensity was not significant. These results are consistent with either a dose-response effect or a threshold level of the dose or dose intensity. CONCLUSIONS: The doses of chemotherapy used to treat breast cancer, especially early breast cancer, should not be reduced if the maximal benefit is to be achieved.

Erythroleukemia in a renal transplant recipient.

A 53-year-old male developed acute erythroleukemia three years after renal transplantation. He had received three years of immunosuppressive therapy with azathioprine. A preleukemia phase associated with chromosome abnormalities was recognized. Azathioprine has been associated with chromosome abnormalities. The chronic stimulation of an abnormal erythroid clone by transplantation may have hastened the development of erythroleukemia.