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.
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.
Hainsworth
J D
JD
Sarah Cannon-Minnie Pearl Cancer Center, Centennial Medical Center, Nashville, Tennessee 37203, USA.
Burris
H A
HA
Morrissey
L H
LH
Greco
F A
FA
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects*; D016190:Carboplatin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011994:Recombinant Proteins; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D019772:Topotecan; D016190:Carboplatin; D017239:Paclitaxel; D000069585:Filgrastim