Phase I trial of docetaxel, carboplatin, and gemcitabine as first-line therapy for patients with high-risk epithelial tumors of müllerian origin

Gynecol Oncol. 2003 Jun;89(3):486-93. doi: 10.1016/s0090-8258(03)00138-0.

Abstract

Objectives: The aim of this study was to assess the feasibility of combining docetaxel, carboplatin, and gemcitabine (DoCaGem) as first-line treatment of ovarian and other müllerian origin tumors.

Methods: Four dose levels were planned for this phase I trial. Treatment consisted of carboplatin on day 1 only, docetaxel on days 1 and 8, and gemcitabine on days 1 and 8, every 21 days.

Results: Nineteen patients were enrolled, of whom 18 were evaluable for toxicity. The first 5 patients enrolled at dose level I (carboplatin AUC 5, 30 mg/m(2) docetaxel, 800 mg/m(2) gemcitabine) experienced no dose-limiting toxicity. At dose level II, 4/4 evaluable patients experienced significant bone marrow suppression that required dose reduction and/or dose delay. Further dose escalation was not attempted, and 9 additional patients were enrolled in dose level I. Of the 67 cycles administered on dose level I, day 8 treatment could not be administered due to bone marrow suppression in 16 cycles (24%), and prolongation of the cycle length from day 22 to day 29 was required in 13 cycles (19%). There were no episodes of febrile neutropenia in evaluable patients and no treatment-related deaths. Grade 3 nonhematologic toxicity (fatigue) occurred in 1 cycle. Response was determined in the 14 evaluable patients who tolerated 4 or more cycles of therapy, with 11 obtaining a complete clinical response and 3 obtaining a partial clinical response.

Conclusions: The DoCaGem regimen is highly active, but myelosuppression at dose level I prevents full dose delivery. Other strategies to combine these three active agents are reasonable to explore.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Epithelial Cells / pathology
  • Female
  • Gemcitabine
  • Humans
  • Middle Aged
  • Mullerian Ducts / pathology*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Paclitaxel / analogs & derivatives*
  • Taxoids*

Substances

  • Taxoids
  • Deoxycytidine
  • Docetaxel
  • Carboplatin
  • Paclitaxel
  • Gemcitabine