Does granulocyte colony-stimulating factor affect survival in patients with advanced non-small cell lung cancer?
BACKGROUND
Platinum-based chemotherapy is standard treatment for patients with advanced lung cancer. The common side effect of this therapy is myelosuppression, for which different stimulating factors are used. In this article, the effect of granulocyte colony-stimulating factor (G-CSF) administration on the survival of patients with unresectable non-small-cell lung cancer (NSCLC) was evaluated.


METHODS
The charts of 127 patients, treated with carboplatin-based chemotherapy, were reviewed for histology, stage, performance status, weight loss, treatment regimen, toxicity, and survival. Eighty patients were stage IIIA/IIIB NSCLC; 47 were stage IIIB (pleural effusion) or stage IV. Eighty-one patients (63%) experienced severe (grades 3 and 4) neutropenia. Forty-two patients received G-CSF, 37 patients for severe neutropenia (14 with febrile neutropenia) and five patients for active infection during chemotherapy.


RESULTS
Preliminary analyses, both unadjusted (median survival, 20 months versus 13.8 months; log-rank test, p = 0.02) and adjusted for covariates of interest (Cox regression, hazard ratio = 0.62, p = 0.03) showed a significant effect of the use of G-CSF on survival, even though the groups were balanced with respect to stage, performance status, weight loss, and dose intensity of chemotherapy. Patients with grades 3 and 4 neutropenia (whether they received G-CSF or not) had a better survival outcome compared to those who did not have neutropenia (median survival, 17.6 months versus 11.9 months, log-rank test, p = 0.04). A landmark analysis showed a marginally significant effect of G-CSF on survival (median survival, 18.6 months versus 15.1 months, log-rank test, p = 0.08), even after adjustment for covariates. The Cox regression with the use of G-CSF defined as a binary time-varying covariate also showed similar results (Cox regression, hazard ratio = 0.67, 95% CI: 0.42-1.04, p = 0.07).


CONCLUSIONS
In this study, the time bias due to the delayed administration of G-CSF contributed to the longer survival of patients receiving G-CSF. Prospective studies are required to determine whether G-CSF has any effect on survival in patients with advanced NSCLC.
Kasymjanova
Goulnar
G
Pulmonary Division, Department of Medicine, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. gkasymja@pne.jgh.mcgill.ca
Kreisman
Harvey
H
Correa
José A
JA
Dajczman
Esther
E
Small
David
D
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D011792:Quebec; D012189:Retrospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
D016179:Granulocyte Colony-Stimulating Factor