Faculty Bibliography

Twenty-one patients with advanced malignant melanoma were treated with dacarbazine at a dose of 800 mg/m2 as a single infusion and dactinomycin at a dose of 1.2 mg/m2 every 3 weeks. Hematologic toxicity was mild and gastrointestinal toxicity was tolerable. The response rate for evaluable patients was 22%, which included both men and women with visceral disease. Three of the four responses were complete. Durations of response were 4, 6, 9, and 48+ months. We conclude that dacarbazine can be safely and effectively given as a single dose along with dactinomycin. The possibility that this combination may be more effective than single agents in obtaining complete responses in patients with visceral disease must be explored further

PCNU, a chloroethylnitrosourea with high alkylating activity, low carbamoylating activity, optimal octanol: water partition coefficient and broad activity in animal systems, was administered to 32 evaluable patients with measurable metastatic melanoma by brief intravenous infusions every six weeks. The initial dose was 75 or 100 mg/m2, with escalation or reduction for toxicity, and a total of 58 evaluable courses were given. Half of the patient population had received no prior chemotherapy. One objective complete response (duration 585 days) and four objective partial responses (durations 55, 169, 405 and 102 days) occurred, the last recorded in a patient previously treated with DTIC. These responses included visceral, nodal and subcutaneous disease. The response rate was 16% with a 95% confidence interval of 5.5 to 33.7%. Thrombocytopenia was dose-limiting and leukopenia was relatively mild. Gastrointestinal toxicity was less severe than expected for a nitrosourea. PCNU has comparable clinical activity to that of other nitrosoureas in patients with advanced melanoma

As of August 1984, 115 women with advanced breast cancer have been randomized to receive a combination of either cyclophosphamide, Novantrone (mitoxantrone) and 5-fluorouracil (CNF) or cyclophosphamide, Adriamycin (doxorubicin) and 5-fluorouracil (CAF). Seventy-one percent of all patients were post-menopausal and 44% of CNF patients and 57% of CAF patients were estrogen receptor (ER) negative. Slightly over 30% of all patients had received hormonal therapy or chemotherapy in an adjuvant setting. Hematologic toxicity was similar in regard to platelet counts but slightly lower nadirs were experienced with CNF therapy than with CAF. However, there were fewer dosage decreases with CNF. Significantly less nausea and vomiting were observed with the CNF regimen compared to CAF. Moreover, alopecia was reduced appreciably in patients who received CNF. The response rate to CNF for the first 38 eligible and evaluable patients was 42%, and for 53 eligible and evaluable patients who received CAF the response rate was 45%, a non-significant difference. Median response durations were similar also, 140 days for CNF and 168 days for the CAF regimen. Time to treatment failure was similar for both regimens. CNF is an effective regimen for patients with advanced breast cancer, with less toxicity than CAF.

The treatment of testicular cancer has undergone considerable evolution since the introduction of cisplatin and the widespread recognition of its curative potential in all stages of disease. Chemotherapy developments that have taken place include substitution of etoposide for vinblastine in some primary combinations and high-dose cisplatin regimens for patients with otherwise poor prognosis. Definition of timed survival restaging and reassessment of the role of radiation has taken place. In early disease stages, dissection of retroperitoneal nodes combined with either a short course of adjuvant chemotherapy or careful monitoring followed by salvage chemotherapy has yielded impressive results (greater than 90% cures) in node positive patients. These results have encouraged trials including careful follow up for patients with negative retroperitoneal and other findings (markers, computerized tomography) on clinical staging alone. Evolution of these treatment strategies should take place within the context of prospectively designed studies. In this brief overview of developments, we point out how the legacy from the successful application of chemotherapy will form the basis for additional achievements which will include the introduction of second-generation drugs and optimization of combined modality strategies.