Phase I clinical trial of weekly docetaxel and exisulind, a novel inducer of apoptosis.

Abstract

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.

PATIENTS AND 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.

• Authors: Agustin A Garcia, Syma Iqbal, David Quinn, Susan Edwards, Heinz Josef Lenz, Jeff Weber
• Journal: Investigational new drugs (Invest New Drugs) Vol. 24 Issue 1 Pg. 79-83 (Jan 2006) ISSN: 0167-6997 [Print] United States
• PMID: 16379039 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Taxoids
• Docetaxel
• Sulindac
• sulindac sulfone

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Apoptosis
• Docetaxel
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (drug therapy)
• Sulindac (administration & dosage, analogs & derivatives)
• Taxoids (administration & dosage)