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

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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

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Authors and Affiliations

  1. The Dean and Betty Gallo Prostate Cancer Center at The Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA

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

  2. Department of Medicine, UMDNJ/Robert Wood Johnson Medical School, New Brunswick, NJ, USA

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

Authors
  1. A. Thalasila
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  2. Elizabeth Poplin
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  3. J. Shih
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  4. Dmitri Dvorzhinski
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  5. T. Capanna
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  6. S. Doyle-Lindrud
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  7. S. Beers
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  8. S. Goodin
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  9. Eric Rubin
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  10. Robert S. DiPaola
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Corresponding author

Correspondence to Robert S. DiPaola.

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Thalasila, A., Poplin, E., Shih, J. et al. A phase I trial of weekly paclitaxel, 13-cis-retinoic acid, and interferon alpha in patients with prostate cancer and other advanced malignancies. Cancer Chemother Pharmacol 52, 119–124 (2003). https://doi.org/10.1007/s00280-003-0644-6

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  • DOI: https://doi.org/10.1007/s00280-003-0644-6

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