Gemcitabine combined with sequential paclitaxel and carboplatin in patients with urothelial cancers and other advanced malignancies

Robert S. DiPaola, Eric Rubin, Deb Toppmeyer, Joseph Eid, Debarah Butzbach, Dmitri Dvorzhinski, Terry Capanna, Marie Cairdella, Joe W. Shih, Susan Goodin, Mary B. Todd

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background: To investigate a novel schedule of gemcitabine (G), paclitaxel (P), and carboplatin (C), based on preclinical studies demonstrating greater activity and decreased toxicity of administering P prior to C. Material/Methods: The effect of the P and C drug sequence on tumor cell viability was assessed with a tetrazolium assay on T24 bladder and DU145 prostate cancer cells. Patients with transitional cell cancer (TCC) and other advanced malignancies were treated with G and P on days 1, 8, and 15 of each 28 day cycle. C was administered on day 2 at an AUC of 5. Doses of G and P were varied among cohorst of three patients. Results: Preclinical studies demonstrated that the sequence of P followed by C induced greater cytotoxicity than the reverse sequence. The recommended phase II dose (RPTD) was defined as 70 mg/m2 P, 300 mg/m2 G, and C with AUC of 5. Therapy was well tolerated; fever and neutropenia occurred in only one patient at the RPTD. Grade 3 thrombocytopenia occurred in 5 of 21 patients treated at the RPTD. Out of all 37 patients treated on study, 9 achieved a partial tumor response (PR) and two patients achieved a complete response (CR). Out of the 15 patients with TCC, six had a PR and two had a CR. Conclusion: Preclinical studies demonstrated that the sequence of paclitaxel followed by carboplatin was more effective than the opposite sequence. Administration of gemcitabine and paclitaxel followed by carboplatin was well tolerated and clinically active. GCP should be compared to other combination regimens under investigation for the treatment of TCC.

Original languageEnglish
Pages (from-to)PI5-PI11
JournalMedical Science Monitor
Volume9
Issue number2
StatePublished - Feb 1 2003

Keywords

  • Bladder
  • Carboplatin
  • Gemcitabine
  • Paclitaxel
  • Transitional cell

ASJC Scopus subject areas

  • General Medicine

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