Improving survival without reducing quality of life in small-cell lung cancer patients by increasing the dose-intensity of chemotherapy with granulocyte colony-stimulating factor support: results of a British Medical Research Council Multicenter Randomized Trial. Medical Research Council Lung Cancer Working Party.
OBJECTIVE
The treatment of small-cell lung cancer patients with good performance status aims to improve survival. Dose-intensification could be a way to achieve improved survival but can be limited by neutropenia and thrombocytopenia. Preliminary, nonrandomized feasibility studies showed that doxorubicin, cyclophosphamide, and etoposide (ACE) could be given every 2 (instead of the usual 3) weeks with granulocyte colony-stimulating factor (G-CSF) (lenograstim; Chugai-Rh¿one-Poulenc, Tokyo, Japan) support. The present multicenter randomized trial was designed to examine whether such dose-intensification improves survival while maintaining acceptable toxicity levels.


METHODS
All patients were randomized to receive six cycles of ACE either every 3 weeks (control [C] group) or every 2 weeks with G-CSF (G group). The standard dose-intensity of ACE was increased by 50% in group G.


RESULTS
Four hundred and three patients (G group: n = 201; C group: n = 202) were randomized. The received dose-intensity was 34% higher in the G group than in the C group. Complete response rates were 40% for the G group and 28% for the C group (P =.02), and overall rates were 78% for the G group and 79% for the C group. Survival was longer in the G group (hazard ratio = 0.80; 95% confidence interval, 0.65 to 0.99; P =.04), survival rates for the G and C groups being 47% and 39% at 12 months and 13% and 8% at 24 months, respectively. Metastasis-free survival, nonhematologic toxicity, and quality of life were similar in the two groups. In the G group, there was less neutropenia but more thrombocytopenia and more frequent blood and platelet transfusions.


CONCLUSIONS
Increasing the dose-intensity of ACE with G-CSF support improved survival while maintaining acceptable toxicity.
Thatcher
N
N
Cancer Division, Medical Research Council Clinical Trials Unit, London, United Kingdom.
Girling
D J
DJ
Hopwood
P
P
Sambrook
R J
RJ
Qian
W
W
Stephens
R J
RJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D011788:Quality of Life; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control
D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide