Modest reductions in dose intensity and drug-induced neutropenia have no major impact on survival of patients with non-small cell lung cancer treated with platinum-doublet chemotherapy

J Thorac Oncol. 2010 Sep;5(9):1397-403. doi: 10.1097/JTO.0b013e3181eba7f9.

Abstract

Background: Previous studies investigating the effect of increased dose intensity and chemotherapy-induced neutropenia in patients with advanced non-small cell lung cancer (NSCLC) have not consistently shown significant survival benefits.

Methods: This retrospective analysis reviewed the outcome of patients receiving palliative chemotherapy for advanced NSCLC (stages III-IV) at the Royal Marsden Hospital. Regimens included cisplatin or carboplatin with either vinorelbine or gemcitabine on days 1 and 8, every 21 days. Patients who received at least four cycles of chemotherapy were classified into groups based on dose intensity, dose reductions, and worst grade of neutropenia for a landmark analysis. Comparisons between these groups for time to progression and overall survival were made by standard univariate and multivariate methods.

Results: One hundred sixty-nine of a total of 190 patients who received more than four cycles of chemotherapy during the period between November 1998 and December 2008 were included. One hundred twenty-five (73.9%) patients received four chemotherapy cycles with the remaining receiving up to six cycles. The median relative dose intensity for platinum was 93.9% (62.1-102%) and for vinorelbine/gemcitabine was 91.7% (37.8-105%). Dose reductions were recorded in 64 patients (37.8%), and 65 patients (38.5%) had grades 3 to 4 neutropenia. There were no statistically significant differences in time to progression and overall survival between any of the subgroups.

Conclusions: This retrospective analysis demonstrates no significant relationship between survival and dose intensity (<90%), modest dose reductions (<20%), or chemotherapy-induced neutropenia in patients receiving standard doublet platinum containing chemotherapy in NSCLC.

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / mortality*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carcinoma, Large Cell / complications
  • Carcinoma, Large Cell / drug therapy
  • Carcinoma, Large Cell / mortality*
  • Carcinoma, Non-Small-Cell Lung / complications
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / mortality*
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Dose-Response Relationship, Drug
  • Female
  • Gemcitabine
  • Humans
  • Lung Neoplasms / complications
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neutropenia / chemically induced*
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives
  • Vinorelbine

Substances

  • Deoxycytidine
  • Vinblastine
  • Carboplatin
  • Cisplatin
  • Vinorelbine
  • Gemcitabine