Phase I evaluation of thio-TEPA in combination with cisplatin for advanced gynecologic malignancies.
Thirty-five patients with advanced gynecologic malignancies were entered into a phase I study evaluating thio-TEPA in combination with cisplatin (50 mg/m2) 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 less than or equal to 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/m2. Thio-TEPA's primary toxicity was myelosuppression; at 50 mg/m2, 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/m2; in 35 cycles at this dose, grade 3 or 4 granulocytopenia occurred in 19, and grade 3 or 4 thrombocytopenia occurred in 10 cycles; median granulocyte nadir was 1100 (range 110 to 3600) and median platelet nadir was 90,000 (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/m2 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/m2) in phase II trials is 40 mg/m2. Cumulative hematologic toxicity may occur with this regimen.
Sandles
L G
LG
Department of Gynecology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Freedman
R S
RS
Raber
M N
MN
Kavanagh
J
J
Edwards
C L
CL
Scott
W R
WR
Wharton
J T
JT
D000380:Agranulocytosis / Q000139:chemically induced; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D004341:Drug Evaluation; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000139:chemically induced
D013852:Thiotepa; D002945:Cisplatin