A phase I study of docetaxel and bexarotene.
BACKGROUND
We conducted a single-arm, dose-escalation, phase 1 clinical trial in order to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of bexarotene in combination with docetaxel.


METHODS
Patients with solid tumors and no other curative treatment options were eligible. Oral bexarotene was taken daily in combination with docetaxel 25 mg/m(2) administered intravenously on days 1, 8, and 15 of a 28-day cycle. The dose of bexarotene started at 200 mg/m(2) and increased by 100 mg/m(2)/dose level, until either a MTD or the final dose of 400 mg/m(2) was reached.


RESULTS
Fifteen patients were enrolled in the study. Median age was 58 years. The majority had non-small-cell lung cancer. The study went to completion without reaching an MTD. Hematological toxicities were mild. Three patients developed grade 3 hypertriglyceridemia, all occurring during the first cycle of treatment. No objective responses were noted. Four patients had stable disease as a best response, 3 with non-small-cell lung cancer and 1 with angiosarcoma.


CONCLUSIONS
Treatment was well tolerated and no DLT was seen at docetaxel 25 mg/m(2) and bexarotene 400 mg/m(2). Given that stable disease was durable in 4 patients, future studies with this combination may be warranted.
Wildi
Jonathan D
JD
Department of Medicine, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Baggstrom
Maria Q
MQ
Suresh
Rama
R
Read
William
W
Fracasso
Paula M
PM
Govindan
Ramaswamy
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D000077610:Bexarotene; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005221:Fatigue / Q000097:blood / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000097:blood / Q000139:chemically induced; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects
D043823:Taxoids; D013764:Tetrahydronaphthalenes; D000077143:Docetaxel; D000077610:Bexarotene