Tumor growth modeling from clinical trials reveals synergistic anticancer effect of the capecitabine and docetaxel combination in metastatic breast cancer

Cancer Chemother Pharmacol. 2011 Dec;68(6):1413-9. doi: 10.1007/s00280-011-1628-6. Epub 2011 Apr 8.

Abstract

Purpose: Most of the cancer chemotherapy treatments employ drugs in combination. For combination treatments, it is relevant to assess interaction between two or more anticancer agents used in clinics. Based on clinical data and using modeling techniques, the work analyzes the pharmacodynamic interaction between capecitabine and docetaxel used in combination in metastatic breast cancer.

Methods: We developed mathematical models to describe tumor growth inhibition profile under treatment based on Phase II and Phase III clinical data of capecitabine and docetaxel in metastatic breast cancer. Model parameters were estimated by population approach with NONMEM(®) on single-agent and combination data. Simulations were performed using MATLAB.

Results: Capecitabine and docetaxel combination in metastatic breast cancer results in a synergistic effect as compared with the simple additive effects of single-agent treatments. Docetaxel is more efficient than capecitabine at the start of treatment but develops resistance faster. Modeling revealed no resistance of capecitabine for the combination data.

Conclusions: Modeling could be a powerful tool to design the most advantageous combination regimen for capecitabine and docetaxel in metastatic breast cancer in order to increase the time before regrowth and decrease the tumor size at regrowth.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Capecitabine
  • Clinical Trials as Topic
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Docetaxel
  • Drug Synergism
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Humans
  • Models, Theoretical
  • Neoplasm Metastasis
  • Taxoids / administration & dosage

Substances

  • Taxoids
  • Deoxycytidine
  • Docetaxel
  • Capecitabine
  • Fluorouracil