Phase I evaluation of thio-TEPA in combination with cisplatin for advanced gynecologic malignancies

• Published in: Gynecologic oncology Vol. 39; no. 2; pp. 139 - 145
• Main Authors: Sandles, Lisa G., Freedman, Ralph S., Raber, Martin N., Kavanagh, John, Edwards, Creighton L., Scott, Wanza R., Wharton, J.Taylor
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.11.1990; Elsevier
• Subjects: Agranulocytosis - chemically induced; Anemia - chemically induced; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy; Cisplatin - administration & dosage; Cisplatin - adverse effects; Drug Evaluation; Female; Genital Neoplasms, Female - drug therapy; Humans; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Thiotepa - administration & dosage; Thiotepa - adverse effects; Thrombocytopenia - chemically induced; Antineoplastic agent; Human; Alkylating agent; Chemotherapy; Polychemotherapy; Treatment; Female genital system; Phase I trial; Female; Advanced stage; Malignant tumor; Female genital diseases
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/0090-8258(90)90421-G

Thirty-five patients with advanced gynecologic malignancies were entered into a phase I study evaluating thio-TEPA in combination with cisplatin (50 mg/m 2) intravenously every 4 weeks. Thirty-four patients were evaluable for toxicity and response, and one was evaluable for toxicity only. Median age was 53 years (range 28–72), and performance status ⩽2. Prior treatment included chemotherapy in 21 patients, radiation in 15, hormonal therapy in 3, and immunotherapy in 1. Thio-TEPA was given to three or more patients at each of the following dose levels: 15, 20, 25, 30, 40, 50, and 60 mg/m 2. Thio-TEPA's primary toxicity was myelosuppression; at 50 mg/m 2, grade 3 or 4 granulocytopenia occurred in 13 of 17 cycles, and grade 3 or 4 thrombocytopenia occurred in 8 of 17 cycles. The maximum tolerated dose (MTD) of thio-TEPA was 40 mg/m 2; in 35 cycles at this dose, grade 3 or 4 granulocytopenia occurred in 19, and grade 3 or 4 thombocytopenia occurred in 10 cycles; median granulocyte nadir was 1100 (range 110 to 3600) and median platelet nadir was 90,00 (range 10,000 to 289,000). Fifteen patients received three or more cycles at one dose level; cumulative myelosuppression was observed in 11. Two cases of partial alopecia occurred at 40 and 60 mg/m 2 thio-TEPA. Responses were as follows: complete response, 5; partial response, 7; stable disease, 14; progressive disease, 8. In 16 patients with ovarian cancer (15 of whom had previously received cisplatin), there were 4 complete responses and 5 partial responses (overall response rate of 56%). The thio-TEPA dose recommended in combination with cisplatin (50 mg/m 2) in phase II trials is 40 mg/m 2. Cumulative hematologic toxicity may occur with this regimen.