Information obtained from quality-of-life assessment in conjunction with phase II testing of new chemotherapeutic agents for metastatic breast cancer can guide quality-of-life evaluation planned in large, randomized future studies.

We report a single institution phase I trial of chimeric (mouse-human) monoclonal antibody (chL6) directed against a tumor-associated cell surface antigen expressed in non-small cell lung, colon, and breast cancer. The results of the study were contrasted with a previous trial of murine L6. ChL6 was administered intravenously to 18 patients with advanced cancer as a single, 4-16 infusion in doses ranging from 350 mg/m2 to 700 mg/m2. One patient received four weekly doses of 350 mg/m2. Patients were followed for side effects, localization of antibody to tumor cells, pharmacokinetics and the development of antibodies against chL6. Side effects associated with treatment were chills, fever, and nausea, which lasted 24-48 hours. Platelet count and absolute leukocyte count fell immediately after treatment, but returned to pretreatment levels by day 7. Localization of chL6 to tumor cells in vivo was seen at 350 mg/m2 and "saturation" at 700 mg/m2 and 350 mg/m2 per week x 4. The pharmacokinetics of this antibody appeared similar to its murine analogue. Human antibodies against chL6 were detected in only 4 of 18 patients. These antibodies were directed against murine variable regent and their titers were lower than those occurring in most patients who received murine L6 in an earlier trial. No tumor reductions were seen. Chimeric L6 appears to be a suitable antibody for delivering anti-tumor agents because of its low immunogenicity and favorable in vivo tumor binding characteristics.

Between April 1986 and March 1987, 42 patients with advanced sarcoma were entered in this multi-institutional trial evaluating ifosfamide plus doxorubicin. The majority of patients had leiomyosarcoma and malignant fibrous histiocytoma although two patients with sarcomas of osseous origin were included. Doxorubicin was administered at a dosage of 60 mg/m2 by continuous push and ifosfamide 5.0 g/m2 by continuous infusion over 24 hours with mesna (7.5 g2 over 36 hours) with courses repeated every 3 weeks until progression, toxicity cumulative doxorubicin dosage of 450 mg/m2. Overall, 15 (36%) patients demonstrated objective remissions including three complete and 12 partial remissions (95% confidence limits, 21.5% to 52.0%). The median duration of remission was 7.0 months and the median survival time for all eligible patients was 8.0 months. Toxicity was predominantly hematologic with the median leukocyte nadir being 1,300 per microliter of blood and documented sepsis in six patients. These data support activity for ifosfamide plus doxorubicin in patients with advanced sarcoma, but the actual contribution of ifosfamide needs to be evaluated through prospective randomized trials which are currently underway.

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Twenty patients with advanced head and neck tumors were entered in a phase II trial of tallysomycin S10b given intravenously at weekly doses of 2.5 mg/m2. All patients had received prior chemotherapy +/- radiotherapy. Sixteen patients were evaluable for response. Two had stable disease for 15 and 22 weeks respectively. None exhibited tumor shrinkage. Non-hematologic toxicities primarily consisted of gastrointestinal intolerance. Mild fever was noted in about half of the patients and increase in serum creatinine was observed in four. Other side effects consisted of decrease in pulmonary diffusion capacity and skin changes. In conclusion, tallysomycin S10b has no activity in previously treated head and neck cancer patients and has a toxicity spectrum similar to that of bleomycin.