Phase I study of vincristine and escalating doses of etoposide

• Published in: Investigational new drugs Vol. 7; no. 2-3; p. 203
• Main Authors: Jackson, Jr, D V, Cruz, J M, Zekan, P J, Caponera, M E, Spurr, C L, White, D R, Richards, 2nd, F, Muss, H B
• Format: Journal Article
• Language: English
• Published: United States 01.07.1989
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Blood Cell Count; Bone Marrow Diseases - chemically induced; Drug Evaluation; Etoposide - administration & dosage; Etoposide - adverse effects; Humans; Neoplasms - drug therapy; Vincristine - administration & dosage; Vincristine - adverse effects
• ISSN: 0167-6997
• DOI: 10.1007/BF00170858

A phase I trial of vincristine and etoposide was designed following the identification of a potentially synergistic antitumor effect in a murine model. The dose of vincristine was fixed (0.5 mg daily for 3 days). Etoposide was given at 1 of 3 total dose levels (250, 500, or 750 mg/m2) per treatment. Each dose was given in 3 equal fractions and each fraction was given daily for 3 days, i.e., 83.3 mg/m2/d x 3d, 166.7 mg/m2/d x 3d, or 250 mg/m2/d x 3d. A total of 31 patients were entered into study including 10, 18, and 3 patients treated at the 250, 500, and 750 mg/m2 dose levels, respectively. Dose-limiting toxicity occurred at the 750 mg/m2 level, in which Grade 4 myelosuppression developed in all of the patients. Life-threatening gram negative sepsis occurred in two of these patients and both required platelet transfusions. Grade 3-4 WBC toxicity was observed in 9 of 16 (56%) evaluable patients treated at the 500 mg/m2 level, but reversal of toxicity was generally rapid with repeat courses given at 3 week intervals in most patients. Non-hematologic toxicity was negligible. Objective responses were observed in 2 of 4 patients with Hodgkin's disease. The starting dose of etoposide recommended for phase II trials of this agent in combination with vincristine is 500 mg/m2; dose escalation may be possible in some patients.