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

✍ Scribed by John D. Hainsworth; Howard A. Burris III; Lisa H. Morrissey; F. Anthony Greco

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 72 KB
• Volume: 85
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/(sici)1097-0142(19990301)85:5<1179::aid-cncr23>3.0.co;2-i

✦ Synopsis

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/m2, 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/m2, 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.