Pharmacology of the paclitaxel-cisplatin, gemcitabine-cisplatin, and paclitaxel-gemcitabine combinations in patients with advanced non-small cell lung cancer

Cancer Chemother Pharmacol. 2006 Oct;58(4):509-16. doi: 10.1007/s00280-006-0191-z. Epub 2006 Mar 7.

Abstract

Purpose: To compare the pharmacology of the paclitaxel-cisplatin, gemcitabine-cisplatin and paclitaxel-gemcitabine combinations in patients with advanced non-small cell lung cancer (NSCLC).

Patients and methods: Twenty-four chemo-naive patients with advanced NSCLC were randomized to receive one of the three regimens. Plasma pharmacokinetics and pharmacologic parameters in mononuclear cells were compared and related to toxicity and efficacy.

Results: Pharmacological parameters of gemcitabine and cisplatin were not influenced by the combination with one of the other agents, while the paclitaxel clearance was significantly lower for the combination with cisplatin as compared to gemcitabine (P=0.024). The percentage decrease in platelets was significantly higher for the gemcitabine combinations (P=0.004) and related to the dFdCTP-Cmax (P=0.030). Pharmacologic parameters were not related to response or survival.

Conclusions: Gemcitabine and cisplatin pharmacology were not influenced by the combination with one of the other agents, while paclitaxel has a lower clearance in combination with cisplatin as compared to gemcitabine.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Area Under Curve
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Cisplatin / pharmacokinetics
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacokinetics
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacokinetics

Substances

  • Deoxycytidine
  • gemcitabine
  • Paclitaxel
  • Cisplatin