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Phase I trial of paclitaxel, carboplatin, and topotecan with or without filgrastim (granulocyte‐colony stimulating factor) in the treatment of patients with advanced, refractory cancer
Author(s) -
Hainsworth John D.,
Burris Howard A.,
Morrissey Lisa H.,
Greco F. Anthony
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990301)85:5<1179::aid-cncr23>3.0.co;2-i
Subject(s) - topotecan , medicine , carboplatin , paclitaxel , regimen , filgrastim , granulocyte colony stimulating factor , pharmacology , refractory (planetary science) , chemotherapy , oncology , toxicity , gastroenterology , surgery , cisplatin , physics , astrobiology
BACKGROUND Topotecan is a new antineoplastic agent with a broad spectrum of activity. The purpose of this Phase I trial was to define the maximum tolerated dose of topotecan when added to the widely used combination of paclitaxel and carboplatin. METHODS Patients with advanced cancer that was refractory or resistant to standard treatments were treated with paclitaxel, carboplatin, and topotecan; doses were escalated in sequential cohorts of patients. After definition of the maximum tolerated dose without cytokines, granulocyte‐colony stimulating factor (G‐CSF) was added and further dose escalation was attempted. RESULTS The maximum tolerated doses were: paclitaxel, 135 mg/m 2 , as a 1‐hour intravenous (i.v.) infusion on Day 1; carboplatin, area under the curve 5.0, on Day 1; and topotecan, 0.75 mg/m 2 , i.v. on Days 1, 2, and 3; the regimen was repeated every 21 days. Myelosuppression, particularly thrombocytopenia, was the dose‐limiting toxicity with this three‐drug combination. Nonhematologic toxicity was uncommon. The addition of G‐CSF did not allow substantial dose escalation because thrombocytopenia was uneffected by this agent. Eleven of 25 patients had major responses to this combination, including 8 of 14 patients with previously treated small cell lung carcinoma. CONCLUSIONS The combination of paclitaxel, carboplatin, and topotecan is feasible, although only relatively low doses of all three drugs can be tolerated due to myelosuppression. This regimen showed a high level of activity in these patients with refractory cancer, and merits further investigation. Cancer 1999;85:1179–85. © 1999 American Cancer Society.