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The purpose of this phase II clinical trial was to evaluate the effectiveness of triazinate and pyrazofurin in the treatment of advanced breast cancer. Although an occasional patient experienced stability of disease, neither agent, as employed in this study, was able to produce an objective antitumor effect in this group of patients with previous chemotherapeutic exposure. At the dosages used in this study, neither agent can be recommended for further treatment of advanced breast cancer.

Twenty-eight patients received diaziquone (AZQ) as a single iv dose ranging from 2 to 27.5 mg/m2 in a phase I study. Myelosuppression was dose-limiting, tended to be cumulative, and was somewhat unpredictable in its occurrence. No pretreatment patient characteristics or chemical abnormalities were found to be consistently related to hematologic toxicity. No objective responses were noted in this study, with most patients having gastrointestinal neoplasms. A single iv injection of 22.5-27.5 mg/m2 of AZQ given every 4-5 weeks would be a suitable initial schedule. Pharmacokinetic studies revealed that the plasma elimination of AZQ was best described by a two-compartment open model with rapid plasma elimination of the parent drug.

Fifty-four patients with metastatic lung cancer were treated with AMSA. Patients with a performance score of 0-1, no prior chemotherapy, and normal liver function received a dose of 35 mg/m2/day iv for 3 days every 4 weeks; patients with a performance score of 2-3, any prior chemotherapy, or abnormal liver functions received a dose of 30 mg/m2/day on the same schedule. Among 53 evaluable patients, responses were noted in one with adenocarcinoma and in two with squamous cell carcinoma (overall response rate, 6%). We conclude that AMSA has limited activity in lung cancer when used in this schedule except perhaps in previously untreated squamous cell carcinoma. Only a limited number of patients with large cell or small cell carcinoma were treated.

Forty-seven patients with squamous cell or small cell lung cancer (28 [60%] of whom had cardiac disease too severe to permit the use of doxorubicin) were treated with cyclophosphamide and VP-16-213 with or without cisplatin. Four of 11 patients with squamous cell (36%) and 19 of 24 patients with small cell (79%) cancers had tumor regressions (eight complete regressions) on the three-drug regimen. Median survival times for the 31 patients with small cell lung cancer were 9 months for those with extensive disease and 12.2 months for those with limited disease. The data suggest that the roles of VP-16-213 and cisplatin need further evaluation in these cell types and that doxorubicin may not be mandatory for successful treatment of squamous cell and small cell lung cancers.

In an attempt to improve upon the 43%-48% regression rates noted for various CAP regimens consisting of cyclophosphamide, doxorubicin (Adriamycin), and cis-diamminedichloroplatinum(II) in various doses and schedules, triazinate was added to that three-drug combination, and the new combination (T-CAP) was evaluated in patients with advanced adenocarcinoma of the lung. T-CAP produced a regression rate of 57% with a 7-week increase in overall median time to progression and a 4-week increase in overall median survival compared to the best of the CAP schedules. More stomatitis and dermatitis were noted with the new combination, but myelosuppression was similar to that of the CAP regimens. These data suggest that further studies with triazinate should be conducted in patients with adenocarcinoma of the lung.