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A toxicologic evaluation of dianhydrogalactitol in man was completed for a 5- and a 10-day schedule. The maximum tolerated dose was 30 mg/m2/day for the 5-day schedule and 21 mg/m2/day for the 10-day schedule. Dose-limiting myelosuppression occurred with both schedules, with leukopenia and thrombocytopenia being observed at median Days 15 and 19 respectively for the 5-day course and median Days 22 and 26 of the 10-day course. Nausea was infrequent and mild. Responses were obtained in one patient with laryngeal carcinoma and in one patient with adenocarcinoma of the lung.

Thirty-five fully evaluable patients with advanced multiple myeloma, refractory to standard chemotherapeutic agents, were entered into a phase II trial with mitoxantrone at a starting dose of 12 mg/m2 iv every 3 weeks. There was one (3%) partial response (lasting 2 1/2 months) in a patient who had received treatment with five different agents, including doxorubicin (total dose, 150 mg/m2). Four additional patients (11%) showed objective evidence of clinical improvement, lasting 4-7 months. Mitoxantrone was well-tolerated with no drug-induced deaths and only moderate to severe leukopenia as the dose-limiting toxicity in the majority of patients. Although mitoxantrone had a low level of activity in this heavily pretreated patient population, consideration should be given to future trials incorporating mitoxantrone into a new drug combination.

Combination induction chemotherapy consisting of vinblastine, bleomycin, and cis-dichlorodiammineplatinum(II) was administered to 126 patients with advanced germ cell tumors of the testis. Following this 4-month induction therapy, maintenance treatment consisting of chlorambucil and actinomycin D alternating monthly with vinblastine was given for an additional 20-month period. Sixty-four patients (51%) achieved a complete remission, while 33 patients (26%) achieved a partial response. Responses were observed in all histologic categories. Seven patients (11%), who were in complete remission, have relapsed at a median time of 5 months. Median duration of remission is greater than 12 months for complete responders and 4 months for partial responders. Significant leukopenia was noted in 57% of evaluable courses and significant thrombocytopenia was noted in 18%. Less than 20% of patients were noted to have nephrotoxicity. Other toxic effects observed were gastrointestinal (42%), dermatologic (15%), pyrexia (14%), neuromuscular (9%), and pulmonary (less than 5%). Several pretreatment parameters are currently being evaluated to determine the impact on complete remission rate and survival.

Gallium nitrate was evaluated by the Southwest Oncology Group in 38 patients with malignant lymphoma, both Hodgkin's disease and non-Hodgkin's lymphoma. Treatment was administered every 2 weeks at a dose of 700 mg/m2, with acceptable toxicity. Seven partial responses (18%) with a duration of 3-11 months were seen: one of seven in Hodgkin's disease and six of 26 in diffuse non-Hodgkin's lymphoma. No responses were noted in nodular types. Gallium nitrate has activity in lymphomas and should be combined with more active drugs for patients who have undergone less intensive prior therapy.

The combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) was reported to be effective in patients with metastatic transitional cell cancer of the urinary bladder. This study was designed to test the effectiveness of the phase II agent amsacrine (m-AMSA) versus CAP in patients previously untreated with systemic chemotherapy, with crossover if no response occurred or at the time of progression. In 23 patients who were randomized to receive CAP, three achieved complete response, seven achieved partial response, six had stable disease, and seven had disease progression. The responses in the 22 patients who received m-AMSA were: one with complete response, three with partial response, six with stable disease, and 12 with progressive disease. The overall response rate to initial CAP therapy was 43% compared to 19% for initial m-AMSA therapy. The median duration of response to CAP was 28 weeks and to m-AMSA was 21 weeks. There were no statistically significant differences in the durations of response or survival times between the groups. The main side effects of CAP were: nausea and/or vomiting, leukopenia, anemia, thrombocytopenia, and renal toxicity. Leukopenia and anemia were the major toxic effects of m-AMSA. Our study supports the justification for testing phase II agent(s) in previously untreated patients with bladder cancer with systemic chemotherapy, provided adequate crossover to a known active single or combination of agents is built into the design of such a trial.