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Twenty-one patients with advanced epidermoid carcinoma of the head and neck region were treated with vindesine. Therapy was started at a dose of 3 mg/m2. Dose escalation by 0.5 mg/m2 weekly to a maximum of 4.0 mg/m2 was permitted when no toxicity was seen. Major dose-limiting toxic effects were neutropenia and peripheral neuropathy. Objective responses were seen in five patients: three partial responses lasting 2, 2, and 3 months, and two minor responses lasting 2 and 5 months.

Seventy-four patients with non-small cell lung cancer were treated in a prospective, randomized trial either with a four-drug combination of cisplatin, doxorubicin, cyclophosphamide, and vindesine (PACE) or with a three-drug combination of cisplatin, cyclophosphamide, and vindesine (PCE). None of these patients had received prior chemotherapy, and all had a Karnofsky performance status of at least 60. Of 68 evaluable patients, 21 (31%) had complete or partial remissions. Response rates for PACE and PCE were similar, and there was no difference in response rates for patients with adenocarcinoma or epidermoid cancer. The median duration of remission was 10 months (range, 2-26+); five patients are still in remission (median, 18+ months; range, 17+ to 26+). The median duration of survival for responding patients (complete or partial) was 18 months. Toxic effects, including mild to moderate myelosuppression, peripheral neuropathy, and nephrotoxicity, were manageable in general. The response rates and remission durations for PACE and PCE are similar to those seen with the two-drug combination of cisplatin and vindesine, and toxic effects are similar. Thus, the addition of doxorubicin and/or cyclophosphamide adds no advantage to the use of the cisplatin and vindesine combination alone.

Adenocarcinoma of unknown primary origin (ACUP) is a common oncologic problem for which there is no standard therapy. Forty-two patients with metastatic tumor were identified as having ACUP after extensive evaluation failed to reveal a primary site of disease. They were treated with an investigational chemotherapy regimen consisting of vindesine and doxorubicin. Of the 38 evaluable patients, six (16%) had major responses to chemotherapy. The median duration of response was 4 months. The median survival of the responding patients has not been reached, but is greater than 8 months. The median survival of the nonresponding patients was 6 months. Vindesine and doxorubicin were well tolerated. The major toxicity was leukopenia, with a median wbc count nadir of 2600/mm. We conclude that the combination of vindesine and doxorubicin has some activity in ACUP, but does not improve the response rate seen with other regimens.

Thirty-three patients with advanced, metastatic APUD tumors (islet cell, carcinoid, or medullary carcinomas of the thyroid) were treated with etoposide as a single agent. Of 29 evaluable patients, four (14%) had partial responses (95% confidence limits, 1%-26%). Toxic effects seen were those previously reported for etoposide as a single agent. Etoposide has activity in APUD tumors; further studies with this agent are indicated.

Vindesine (VDS) is a new semisynthetic vinca alkaloid which has demonstrated therapeutic activity against a variety of solid tumors. A phase II trial of this agent was performed in patients with advanced malignant mesothelioma. VDS at a dose of 3 mg/m2 was given iv once weekly for 4-6 weeks and then every 2 weeks thereafter. Only one of 17 evaluable patients had a partial remission, lasting 5 months (95% confidence limits, 0%-17%). Toxic effects of VDS included leukopenia, peripheral neuropathy, and alopecia. VDS has minimal activity in malignant mesothelioma.