Richards F nd

Lack of potentiation of vincristine-induced neurotoxicity by VP-16-213

DUE TO A RECENT ALARMING REPORT suggesting that the severe neurotoxicity observed following treatment with a multiagent chemotherapy regimen might be due to the interaction of vincristine and VP-16–213, the neurologic toxicity data from a randomized trial conducted by the Bowman Gray School of Medicine and the Piedmont Oncology Association in small cell carcinoma of the lung have been analyzed. Of 102 patients evaluable for toxicity, 50 were treated with a combination of cyclophosphamide, adriamycin, and vincristine (CAV) and 52 received this regimen plus VP-16–213. Vincristine dosage was the same in both arms of the study. When analyzed by severity, neurologic complications were similar in both treatment groups: Grade 1–2 neurotoxicity occurred in 55% of patients on both arms and grade 3–4 neurotoxicity was observed in six (12%) patients on the CAV arm and four (8%) on the CAV-VP-16–213 arm. Addition of VP-16–213 to vincristine did not potentiate vincristine-induced neurotoxicity when administered in this dose-schedule relationship.

Bone marrow evaluation in small cell lung cancer.

The records of 87 patients with small cell lung cancer were reviewed. Patients were clinically staged with bone marrow aspirate and biopsy as well as radionuclide scans of bone, liver, and brain. Extrathoracic spread was noted in 54% (47/87) and limited disease in 46% (40/87). The bone marrow evaluation was positive in 13/62 patients (21%) and seven of these thirteen patients had normal bone scans (54%). Of these seven patients, five had no other evidence of distant metastases and their survival was 7-10 months, considerably shorter than patients found to have limited disease. Bone marrow examination appears to complement radionuclide scanning in the initial staging of patients with small cell carcinoma of the lung and provides important prognostic information.

Cytotoxic chemotherapy and androgen priming in patients with advanced carcinoma of the prostate. A phase II trial of the Piedmont Oncology Association.

TWENTY-THREE PATIENTS WITH ADVANCED PROSTATIC CANCER refractory to hormonal therapy were entered into a phase II study of cytotoxic chemotherapy combined with androgen priming. Patients received vincristine 0.5 mg on day 1; fluoxymesterone 10 mg p.o. TID, days 1–5; metnotrexate 4 mg/m2 p.o., days 1–7; and cyclophosphamide 500 mg/m2 I.V., day 8. Patients entered had no prior chemotherapy, most were symptomatic but ambulatory (18/23), and almost all had bone metastases (22/23). There were two stable responses and 14 progressions in 16 patients evaluable for response. Hematologic and gastrointestinal toxicities were substantial. Androgen priming was an unsatisfactory method of improving response in this trial.

A phase II study of dibromodulcitol (DBD) in stage IV melanoma.

TWENTY-FOUR PATIENTS WERE EVALUATED IN A NON-randomized study to assess the effectiveness of dibromodulcitol (DBD) in Stage IV melanoma. Patients received 100 mg/m2 of DBD orally for 35 days. The dose was escalated to 130 mg/m2 and then to 160 mg/m2 if no significant hematologic toxicity occurred. There were no objective responses, including six patients who had had no prior chemotherapy. Five patients (21%) remained stable. Median survival was 151 days. Survival favored females, nonvisceral involvement pretherapy, and patients with a disease-free interval (DFI) of greater than 1 year. None of these advantages was statistically significant. Toxicity was predominantly hematologic, but nausea, vomiting, shortness of breath, and diarrhea were also seen. Oral DBD, using this dose and schedule, does not appear efficacious in advanced disseminated melanoma.