Eighteen patients with unresectable bronchogenic carcinoma were treated with amphotericin B (7.5 mgim' on day I , I5 mg/m2 on day 2, and 30 mg/m2 on days 3 and 4) plus BCNU (250 mg/m2 on day 4 following amphotericin B) with courses of therapy repeated every 8 weeks. All patients had metastatic disease, and S had received prior chemotherapy. Antitumor responses were observed in 8 patients. Six patients had partial responses (>SO% decrease in tumor area): I of 3 with small cell undifferentiated carcinoma, 1 of 4 patients with large cell undifferentiated carcinoma, 2 of 7 patients with adenocarcinoma, and 2 of 4 patients with epidermoid carcinoma. Two patients had objective improvement (25-S0% decrease in tumor area): 1 with small cell undifferentiated carcinoma and 1 with epidermoid carcinoma. The median duration of remission was 3 months. The median duration of survival was 7 months for patients achieving partial response, and only 2 months for other patients. Myelosuppression was the dose limiting toxicity. One patient died with hepatocellular dysfunction, possibly related to BCNU. Transient hypotension was observed in 2 patients. We conclude that amphotericin B plus BCKU produced an encouragingly high response rate in patients with hronchogenic carcinoma, and that a randomized phase 111 trial is warranted to determine whether amphotericin B enhances the antitumor effects of nitrosoureas or other known antitumor agents.
Cancer 4 5 6 -10, 1980.
MPHOTERICIN B is a polyene antibiotic which has
A undergone initial testing in antineoplastic therapy as a result of laboratory observations. It enhances the uptake of other antibiotics into fungi6 and the uptake of antineoplastic drugs such as actinomycin Di and nitrogen mustard" into tumor cells. Amphotericin B plus BCNUt produced long-term cures of transplanted A K R leukemia which were not observed with either agent used alone.R This phenomenon was thought to be caused by immunological enhancement by amphotericin B since whole-body