Docetaxel in combination with carboplatin for the treatment of advanced non-small cell lung carcinoma: a multicentre phase I study

Eur J Cancer. 2000 Apr;36(6):742-7. doi: 10.1016/s0959-8049(00)00005-8.

Abstract

Docetaxel and carboplatin have shown in vitro and in vivo activity against non-small cell lung cancer (NSCLC). A phase I study was conducted in order to determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of their combination. Chemotherapy-naïve patients with stage IIIB and IV NSCLC, age<75 years old, performance status (WHO) 0-2, with adequate bone marrow, renal, liver and cardiac function, were treated with docetaxel and carboplatin. Docetaxel was given at escalated doses starting from 70 mg/m(2) with increments of 10 mg/m(2) followed by carboplatin also administered at escalated doses starting from AUC 5 to 7 AUC (mg/ml. min); the regimen was administered every 3 weeks. No colony-stimulating factor or intrapatient escalation was allowed. The toxicity of the regimen was assessed during the first chemotherapy cycle. 35 enrolled patients received a total of 114 chemotherapy cycles (median 3 cycles/patient; range: 1-8). All patients were assessable for toxicity. Neutropenia was the main dose-limiting toxicity of the regimen; overall, grade 3/4 neutropenia occurred in 16 (14%) cycles; six (5%) neutropenic episodes were complicated with fever but there was no septic death. Grade 3/4 thrombocytopenia was uncommon (two cycles; 2%). Grade 3/4 diarrhoea occurred in 5 (14%) patients whilst neurotoxicity, fatigue and mucositis were extremely uncommon. Two MTDs were defined: the MTD(1) was docetaxel 80 mg/m(2) and carboplatin AUC 7 mg/ml x min whilst MTD(2) was docetaxel 100 mg/m(2) and carboplatin AUC 6 mg/ml x min. The combination of docetaxel and carboplatin is a feasible and well-tolerated outpatient regimen for the treatment of patients with locally advanced and metastatic NSCLC. This regimen merits further investigation in phase II trials.

Publication types

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

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Female
  • Hematologic Diseases / chemically induced
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Paclitaxel / analogs & derivatives
  • Taxoids*

Substances

  • Taxoids
  • Docetaxel
  • Carboplatin
  • Paclitaxel