Phase I and preliminary phase II observations of high-dose intermittent 6-thioguanine

6-Thioguanine was administered iv or orally to 66 patients on an intermittent schedule, one dose every 3 weeks. Doses were gradually escalated until moderate toxicity was observed. The dose-limiting toxic effects were myelosuppression and azotemia. The recommended starting doses for phase II or III studies were 700 mg/m ² iv and 1400 mg/m ² orally. Nephrotoxicity and myelosuppression were reversible in all clearly drug-related instances. Myelosuppression was transient, with nadir blood cell counts observed 10-14 days after drug administration. No cumulative toxicity was observed. Antitumor responses were observed in five of 21 evaluable patients with metastatic colorectal carcinoma including two of four previously untreated patients with that disease. Other than a transient response in a patient with endometrial carcinoma, who received her drug orally, all other responses were observed in patients treated iv with 6-thioguanine. Further phase II trials, particularly in colorectal carcinoma, are recommended.