A phase I and pharmacokinetic study of exisulind and docetaxel in patients with advanced solid tumors

Samir E. Witta, Daniel L. Gustafson, A. Scott Pierson, Alexander Menter, Scott N. Holden, Michele Basche, Martha Persky, Cindy L. O'Bryant, Chan Zeng, Anna Baron, Michael E. Long, Amy Gibbs, Karen Kelly, Paul A. Bunn, Daniel C. Chan, Patrick Pallansch, S. Gail Eckhardt

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Purpose: Exisulind (sulindac sulfone, FGN-1, Aptosyn) is a sulindac metabolite that induces apoptosis via inhibition of cyclic GMP- phosphodiesterase. This agent demonstrated tumor growth inhibition in rodent models of colon, breast, prostate, and lung carcinogenesis. In an orthotopic model of human non-small-cell lung cancer, the combination of exisulind and docetaxel prolonged survival in athymic nude rats, forming the basis of this phase I combination study. Experimental Design: This study evaluated the toxicity and pharmacokinetics of combining exisulind (150-250 mg) given orally twice daily and docetaxel (30-36 mg/m2) administered intravenously on days 1, 8, and 15 of a 4-week cycle. Results: Twenty patients with a range of advanced solid tumors (median age, 59 years; age range, 35-77 years; median performance status, 1) received a total of 70 courses. Observed adverse events were mild to moderate, and there was no dose-limiting toxicity at any level. Grade 3 gastrointestinal toxicities were present in 10 of the 70 cycles (10%) and included nausea, vomiting, dyspepsia, and elevated alkaline phosphatase. Neutropenia was present in four cycles in patients treated with a docetaxel dose of 36 mg/m2. Pharmacokinetic analysis did not demonstrate a clear effect of exisulind on docetaxel pharmacokinetics and vice versa. Relationships were evident between the plasma concentration of exisulind and the development of grade 2 or greater toxicities. One third of patients maintained stable disease for 3 to 12 cycles, but no objective responses were observed. Conclusions: The combination of docetaxel (36 mg/m2, weekly) and exisulind (500 mg/d) was reasonably well tolerated, and it is undergoing phase II testing in patients with non-small-cell lung cancer.

Original languageEnglish (US)
Pages (from-to)7229-7237
Number of pages9
JournalClinical Cancer Research
Issue number21
StatePublished - Nov 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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