Amphotericin B plus 1,3-BIS (2-chloroethyl)-1-nitrosourea (BCNU-NSC NO. 409962) in advanced cancer.Phase I and preliminary phase II results

Abstract

Twenty-one patients with advanced metastatic cancer received amphotericin B (AmB) plus BNUC in a Phase I chemotherapy trial. Of 11 patients with measurable metastases from bronchogenic carcinoma, five had partial antitumor responses lasting 1.5 to 12+ months, and one had objective improvement. Only two of six patients with other types of tumors had objective improvement of short duration. No consistent evidence of immunologic stimulation was observed in eight patients studied. These results suggest that amphotericin B may increase the therapeutic ratio of BCNU, and further trials of this new concept in chemotherapy of advanced tumors are in progress. The dose-limiting toxicity was myelosuppression, usually thrombocytopenia. No enhancement of BCNU toxicity by the addition of AmB was observed. The recommended dose for future studies is: AmB, 7.5 mg/m2 on day 1, 15 mg/m2 on day 1, 30 mg/m2 on days 3 and 4; plus BCNU, 250 mg/m3 on day 4. The regimen is repeated every 6 to 8 weeks.

Chemotherapy of Unresectable or Recurrent Metastatic Malignant Melanomas: An Update

“…Also, in several lymphoid malignancies in mice, amphotericin B has shown enhanced chemotherapeutic effects. These data have led to clinical trials of amphotericin B as an adjuvant chemotherapy in cancers of lungs and breasts ,…”

“…These data have led to clinical trials of am photericin B as an adjuvant chemotherapy in cancers of lungs and breasts. 54,55 Our laboratory has been studying the interactions in vitro of amphotericin B and common cytotoxic agents in cases of leukemias and malignant melanomas of human beings. These studies suggest there is promise of benefit in malignant melanomas.…”

The effect of oral administration of amphotericin B on the incorporation of 5-fluorouracil into human gastric cancer tissue.

“…As shown in Table 1, in 5 of the 7 cancer cases that received combination therapy, the ratio of the 5-FU content of the cancer tissue to that of the normal tissue surrounding the lesion was higher than the ratio obtained in 4 control cases. Presant et al (1976) reported a combination therapy using AmB and BCNU. Nakazawa et al (1978) reported that an intravenous drip of AmB had promoted the incorporation of neocarzinostatin (NCS) into human gastric tissues.…”

The promoting effect of amphotericin B on the incorporation of neocarzinostatin into human gastric cancer tissue.

“…As shown in Table 1, in 4 of the 6 cancer cases that received combination therapy, the NCS titers of the cancer tissues were higher by 10 to 80% than those of the normal tissues surrounding the lesions. Presant et al (1976) reported a combination therapy using AmB and BCNU. Nakazawa et al (1978) reported that an intravenous drip of AmB had promoted the incorporation of NCS into human gastric cancer tissues.…”