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.
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.
Brunetto
Andre T
AT
Royal Marsden NHS Foundation Trust, Department of Medicine, Royal Marsden Hospital, Downs Road, Sutton, Surrey, UK.
Carden
Craig P
CP
Myerson
James
J
Faria
Ana Luisa
AL
Ashley
Sue
S
Popat
Sanjay
S
O'Brien
Mary E R
ME
D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018287:Carcinoma, Large Cell / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
D003841:Deoxycytidine; D014747:Vinblastine; D016190:Carboplatin; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine