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.

Eighty-two patients with metastatic tumor received a therapeutic regimen consisting of BCNU, 100 mg/m2, and cyclophosphamide, 400 mg/m2, both intravenously on day 1, followed by adriamycin, 40 mg/m2, on day 2. Treatment was repeated every 4 weeks. Of 14 evaluable patients with adenocarcinoma of the breast, all resistant to previous chemotherapy and 12 resistant to a five-drug combination chemotherapy program, 12 had objective responses of which seven were good partial responses. Osseous, visceral, and cutaneous metastases responded equally well. Overall, 53% of 68 evaluable patients had objective responses, and 32% had complete or good partial responses. The most encouraging results were in patients with carcinoma of the head and neck, ovarian carcinoma, and multiple myeloma refractory to standard therapy. Significant responses were observed in previously untreated patients with epidermoid carcinoma of the lung, carcinoma of the prostate, and carcinoma of undermined primary. Remissions lasted a median of 5 months. Myelosuppression was moderate in degree and was maximal 2 weeks after treatment. Cumulative thrombocytopenia was apparent but not dose limiting with repeated courses.

Thirty-two evaluable patients with metastatic carcinoma of the breast received chemotherapy consisting of BCNU plus cyclophosphamide followed in 18 hours by Adriamycin. Treatments were repeated every 4 weeks. Complete or partial responses were observed in 14 patients (43.7%) and in 12 of 27 drug-resistant patients (44.4%). An additional 26% of patients had objective improvement, for an overall objective response rate of 70.4% in drug-resistant patients. Skin, lymph node, and soft tissue metastases more frequently responded to therapy, while hepatic, peritoneal, and osseous metastases responded with an intermediate frequency. Pulmonary, pleural, and central nervous system metastases did not respond to therapy. The median duration of complete and partial responses was 6.8 months, and the median survival of these patients was 9.6 months. Overall, the median survival of all patients in this study was 6.5 months. The dose-limiting toxicity was myelosuppression, particularly granulocytopenia. Congestive heart failure and stomatitis were rare. This combination of drugs is a reasonably well-tolerated regimen for treating advanced breast carcinoma in an ambulatory setting, and produces a high rate of objective antitumor response of moderate duration.

Forty-four patients with advanced carcinoma of the head and neck were treated with cyclophosphamide, 400 mg/m2 plus BCNU, 100 mg/mz day 1 followed by adriamycin 40 mg/m* day 2, with therapy repeated every 4 weeks. Of 31 evaluable patients, there were 1 complete response, and 10 partial responses (35%). Four of 8 patients without prior chemotherapy had complete or partial responses, as did 7 of 23 patients who had received prior chemotherapy. The mean survival for patients with partial responses was 8.8 months, and for patients with stable disease was 7.8 months. The mean time to progression for patients with partial responses was 5.4 months, and for patients with stable disease was 3.2 months. Granulocytopenia was the dose limiting toxicity, and patients with increasing degrees of myelosuppression appeared to have higher quality responses and longer survival. The ABC treatment program is useful in the palliative management of patients with advanced carcinoma of the head and neck.Cancer 44:1571-1575, 1979. LTHOUGH IN GENERAL the chemotherapyA of advanced head and neck cancer has produced a small number of remissions of short duration,2 several recent studies suggest that combination chemotherapy may be able to achieve more frequent control of disease initially.3*7-s However, there remains a need for development of therapy which is not crossresistant with methotrexate-containing treatments for patients with this disease. In a prior study,4 utilizing a combination of adriamycin, BCNU and cyclophosphamide based on experimental tumor data, we observed several encouraging responses in patients with carcinoma of the head and neck. Therefore, a Phase I1 study of BCNU and cyclophosphamide on day 1 followed by adriamycin on day 2 (ABC) was continued in patients with head and neck carcinoma. This manuscript summarizes our experience with that treatment

A phase II trial of Adriamycin, BCNU, and cyclophosphamide was performed in 29 patients with advanced prostatic carcinoma (Southeastern Cancer Study Group protocol SEG 76 PR 0102P). Therapy consisted of BCNU 100 mg/m2, plus cyclophosphamide, 300 mg/m2 i.v., on day 1, followed by Adriamycin, 30 mg/m2 i.v., on day 2. Therapy was repeated every four weeks. In 27 evaluable patients refractory to prior estrogen therapy, one patient had a complete response, six patients had partial responses, and two patients had objective improvement (complete plus partial response rate 26%, and overall response rate 33%). Responders had a median time to progression of disease of 5.5 months, compared with a median time to progression of 4.0 months for those patients with stable disease. The median survival of responders was 9.3 months, compared with 6.7 months for stable disease and 3.9 months for patients with progression. Patients with higher pretreatment performance status did not have higher response rates. No life-threatening toxicity was observed. Only five patients had nadir platelet counts below 50,000/mm3, and only six patients had nadir granulocyte counts below 750/mm3. This regimen palliates the effects of hormone-resistant metastatic prostatic carcinoma.