Phase I trial of intermittent high-dose dacarbazine.

A phase I study was conducted with dacarbazine (DTIC) protected from light and administered iv as a single dose every 3 weeks. Eighteen patients received 47 courses of DTIC, with doses ranging from 850 to 1980 mg/m2. Hypotension was the dose-limiting toxic effect and it may be secondary to the citric acid present in the pharmaceutic preparation of DTIC. Sporadic myelosuppression was seen at doses greater than 1380 mg/m2. Other side effects noted were nausea and vomiting, acute diarrhea, headache, a "flu-like" syndrome, and a hypersensitivity reaction to sunlight. No antitumor activity was found. The results of this study indicate that this may be a qualitatively different way of giving DTIC, and that the side effects of this drug may be intermingled with those of citric acid in this particular schedule. If the conventional pharmaceutic preparation of this drug is not modified, further studies with high-dose DTIC protected from light should be discouraged.