Phase I-II study to evaluate safety and efficacy of capecitabine (Xeloda) and exisulind (Aptosyn) combination therapy in patients with metastatic breast cancer

L. Pusztai, K. M. Nealy, P. Pallansch, E. Rivera, V. Valero, M. Cristofanilli, G. N. Hortobagyi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Exisulind is a selective inducer of apoptosis in neoplastic cells and also potentiates the cy totoxic activity of chemotherapy drugs in preclinical models. The primary objective of the phase I part of this study was to determine a safe dose for combination therapy with capecitabine (C) and exisulind (E) in patients with metastatic breast cancer who failed both anthracycline and taxane chemotherapy. Phase I results are reported here. Design: Two dose levels were tested; level 1, C 1000 mg/m2 po BID × 14 days + E 125 mg po BID and level 2, C 1000 mg/m2 po BID × 14 days + E 250 mg po BID daily in 21-day cycles. The first cohort of 5 patients was entered at dose level 1. If no dose-limiting toxicity (DLT, > 33% of non-hematologic grade >3 or hematological grade 4 toxicity) was seen after the first cycle, then the second cycle was given at dose level 2. If > 3 patients were eligible for dose escalation, then additional 5 patients were accrued to start therapy at dose level 2. Dose modification for C followed the package insert. E was to be reduced only for > grade 2 liver toxicity or prolonged non-hepatic toxicity. Results; Thirteen patients were accrued and completed at least 1 full cycle. Three of 5 patients in the first cohort were advanced to dose level 2 and 8 additional patients were accrued to start treatment at level 2. Twenty-two cycles, 7 at dose level 1 and 15 at dose level 2 were given. Six (54% ) of the 11 patients at level 2 required dose reduction. Three patients for > grade 2 reversible liver enzyme elevation assumed to be related to E, 6 for C-related toxicity and 2 patients had toxicity from both. DLT were grade 3 hand-foot syndrome and diarrhea. Grade 2 fatigue, nausea and myalgia was also reported. No grade > 3 hematological toxicity was seen. Of the 9 patients who completed 2 cycles of therapy, 4 had stable disease and 5 progressed. Conclusion: No unexpected toxicity was seen. Treatment at dose level 2 resulted in significant toxicily, all symptomatic adverse events were consistent with toxicity from capecitabine. Currently patients are accrued at level 1 to explore toxicity and efficacy of this combination further.

Original languageEnglish (US)
Pages (from-to)285
Number of pages1
JournalBreast Cancer Research and Treatment
Issue number3
StatePublished - 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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