Phase II trial of paclitaxel and topotecan with granulocyte colony-stimulating factor support in stage IV breast cancer

J Clin Oncol. 1998 Jun;16(6):2032-7. doi: 10.1200/JCO.1998.16.6.2032.

Abstract

Purpose: This multicenter phase II trial investigated the efficacy and safety of a combination of paclitaxel and topotecan in patients with pretreated metastatic breast cancer. Plasma levels of paclitaxel and topotecan were obtained during cycle 1 to correlate pharmacokinetic parameters with toxicity.

Patients and methods: Paclitaxel was administered intravenously (i.v.) at 230 mg/m2 over 3 hours on day 1 followed by topotecan 1.0 mg/m2 i.v. over 30 minutes on days 1 to 5. Patients received an abbreviated premedication regimen that consisted of ranitidine 50 mg, diphenhydramine 50 mg, and a single 20-mg dose of dexamethasone, all administered i.v. 30 minutes before paclitaxel. Granulocyte colony-stimulating factor (GCSF) was administered at 5 micrograms/kg/d subcutaneously starting on day 6 and continuing until the absolute granulocyte count (AGC) was greater than 10,000/microL. Plasma paclitaxel and topotecan concentrations were assessed during the first cycle using limited-sampling strategies.

Results: Seventeen patients were treated. The majority had visceral metastases. Four patients experienced neutropenic fever and one had mild bronchospasm. Only one partial response (PR) was observed. Nadir AGC correlated strongly with both duration of paclitaxel levels greater than 0.05 mumol/L and maximum concentration (Cmax) of paclitaxel.

Conclusion: This regimen does not produce a response rate superior to that expected with single-agent paclitaxel at doses that do not require growth factor support.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Humans
  • Middle Aged
  • Paclitaxel / administration & dosage*
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacokinetics
  • Regression Analysis
  • Topotecan / administration & dosage*
  • Topotecan / adverse effects
  • Topotecan / pharmacokinetics
  • Treatment Outcome

Substances

  • Granulocyte Colony-Stimulating Factor
  • Topotecan
  • Paclitaxel