A phase I trial of weekly paclitaxel, 13-cis-retinoic acid, and interferon alpha in patients with prostate cancer and other advanced malignancies

A. Thalasila, Elizabeth Poplin, J. Shih, Dmitri Dvorzhinski, T. Capanna, S. Doyle-Lindrud, S. Beers, S. Goodin, Eric Rubin, Robert S. DiPaola

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Purpose: Based on prior studies demonstrating the effect of 13-cis-retinoic acid and interferon alpha (CRA/IFN) in decreasing the expression of the antiapoptotic protein bcl-2, our prior clinical study of CRA/IFN with paclitaxel (TAX) administered every 3 weeks, and data demonstrating increased activity of weekly TAX against prostate cancer, we designed a phase I study of weekly TAX in combination with CRA/IFN in patients with prostate cancer and other advanced malignancies. To develop a marker of drug effect, we assessed bcl-2 downregulation in patient peripheral blood mononuclear cells (PBMC). Methods: Enrolled in the study were 14 patients with prostate cancer or other advanced malignancies, and 13 were treated with 1 mg/ kg CRA on days 1 and 2, 6 MU/m2 IFN subcutaneously on days 1 and 2, and TAX at increasing doses on day 2 each week for 6 weeks out of an 8-week cycle. The effect of CRA/IFN on bcl-2 expression was assessed in PBMCs by immunoblotting. Results: The combination of CRA/IFN and TAX was well tolerated. Dose-limiting toxicities (DLT) in the first cycle of therapy included one patient with fever and neutropenia, and one patient with grade 4 hypertriglyceridemia. The recommended phase II dose of TAX in this combination was 80 mg/m2. Of 13 patients assessable by tumor markers or scans, 5 had stable disease and 2 had a biochemical partial response including a patient with a decrease in PSA of >50% while on study. The assessment of patient PBMC bcl-2 was feasible in ten patients. Conclusions: This is the first study in which the safety and clinical activity of weekly TAX combined with CRA/IFN has been demonstrated. The assessment of PBMC bcl-2 is feasible in this weekly chemotherapy schedule.

Original languageEnglish
Pages (from-to)119-124
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume52
Issue number2
DOIs
StatePublished - Aug 1 2003

Keywords

  • 13-Cis-retinoic acid
  • Bcl-2
  • Interferon alpha
  • Paclitaxel
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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