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

We hypothesized that cyclophosphamide and cis-platinum, without adriamycin, which had been used in previous studies, may be equally efficacious, but less toxic. We treated 27 patients with non-small cell bronchogenic carcinoma with the combination of cyclophosphamide and cis-platinum. We report six responses (25% response rate), with median survival of 79 weeks as compared to 28 weeks in nonresponders (p less than 0.01). Our regimen had acceptable hematologic toxicity and tolerable gastrointestinal toxicity. However, cumulative nephrotoxicity and neurotoxicity were observed. We conclude that cyclophosphamide and cis-platinum may compare favorably to the cyclophosphamide, adriamycin and cis-platinum combination, with respect to response and toxicity

Twenty-nine patients (two with small bowel cancer and 27 with colorectal cancer) were treated with a sequential 5-FU-hydroxyurea combination following the suggestion of schedule-dependent synergism in experimental systems. No enhanced toxicity was observed, but the response rate was only 4%. Seven additional patients manifested greater than or equal to 50% declines in CEA, but caution must be used in interpreting such changes as antitumor activity

A phase II study of ip 5-FU was performed in 14 patients with ovarian cancer who were refractory to systemic chemotherapy including prior iv 5-FU in 12 of the patients. 5-FU was administered via a semipermanent Tenckhoff peritoneal dialysis catheter. The starting concentration of 5-FU in the dialysate was 4 mM. The patients received eight consecutive 2-L exchanges, each of 4-hour duration, for a total of 36 hours including time for instillation and drainage. Treatment courses were repeated every 2 weeks for six cycles or until disease progression occurred. A total of 69 cycles of ip 5-FU were administered to 14 patients. There was one complete response to therapy documented by second-look laparotomy. While the response rate was only 7%, in seven of eight (88%) patients with small volume disease (tumor masses less than 2.0 cm in diameter), there was no evidence for disease progression while receiving ip 5-FU therapy. In this phase II trial, the major toxic effect of ip 5-FU was abdominal pain. While there were no cases of documented bacterial peritonitis, all of the patients experienced some degree of abdominal discomfort while receiving therapy. Fifty percent of the patients had severe abdominal pain with at least one cycle of therapy. Other toxic effects included myelosuppression, mucositis, nausea and vomiting, and skin rash. The results of this study indicate that ip 5-FU should be further evaluated in patients with ovarian cancer who have a small volume of disease and who have not had prior therapy with 5-FU