Phase I clinical trial of weekly docetaxel and exisulind, a novel inducer of apoptosis.
BACKGROUND
The objective of this phase I study was to determine the maximal tolerated dose (MTD) of the combination of weekly docetaxel and exisulind in patients with advanced solid tumors.


METHODS
Patients with advanced or refractory solid tumors were treated with intravenous weekly docetaxel with daily oral exisulind. The following dose levels (docetaxel/exisulind) were explored: 30-mg/m2/200 mg po bid, 35/200, 35/250 and 40/250. Docetaxel was administered weekly for 6 weeks followed by 2 weeks off, and exisulind was taken twice daily. Each cycle was 8 weeks.


RESULTS
Eighteen patients were enrolled in the study. All of them had received prior systemic therapy. Most patients had either melanoma or carcinomas of the upper gastrointestinal tract. A total of 31 cycles of therapy were administered. DLTs were grade 3 diarrhea, anorexia and fatigue and grade 3 cutaneous toxicity at dose level 4 (40/250). Myelosuppression was mild. Fatigue and gastrointestinal toxicity (anorexia, dyspepsia, nausea, abdominal pain and diarrhea) represented the most common toxicities. However, grade 3 and grade 4 toxicities were uncommon. There were no treatment related deaths. No objective responses were observed and five patients achieved stable disease.


CONCLUSIONS
The recommended dose for phase II studies is weekly docetaxel 35 mg/m2 for 6 weeks followed by 2 weeks off in combination with oral exisulind 250 mg po bid. This combination is feasible and well-tolerated at these doses.
Garcia
Agustin A
AA
University of Southern California Keck School of Medicine, Kenneth Norris Jr. Comprehensive Cancer Center, Los Angeles, CA, USA. Agustin.Garcia@cshs.org
Iqbal
Syma
S
Quinn
David
D
Edwards
Susan
S
Lenz
Heinz Josef
HJ
Weber
Jeff
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D013467:Sulindac / Q000008:administration & dosage / Q000031:analogs & derivatives; D043823:Taxoids / Q000008:administration & dosage
D043823:Taxoids; D000077143:Docetaxel; D013467:Sulindac; C025463:sulindac sulfone