Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group.
OBJECTIVE
The primary objective of this randomized prospective study was to compare the survival of limited-stage small-cell lung cancer (SCLC) patients treated with chemotherapy alone or chemotherapy plus thoracic radiotherapy (TRT). A secondary objective was to determine the effect of consolidation chemotherapy on survival.


METHODS
This multiinstitutional phase III study included 386 patients with limited-stage SCLC. All patients received cyclophosphamide 1,000 mg/m2, doxorubicin 40 mg/m2, and vincristine 1 mg/m2 (CAV) every 3 weeks for six cycles. Irradiated patients received 30 Gy in 10 fractions during weeks 1 and 2 of chemotherapy. Fifteen Gy in five fractions was administered during week 7 (total dose, 45 Gy). Following CAV, responding patients were randomized to receive two cycles of consolidation chemotherapy (cisplatin 20 mg/m2/d for 4 days plus etoposide 100 mg/m2/d for 4 days) or observation.


RESULTS
Complete (46% and 38%; P = .14) and overall response rates (67% and 64%; P = .58) were not statistically significantly different. Although not significantly different, median (14.4 v 12.8 months) and 2-year survival (33% v 23.5%) rates favored the irradiated patients. Grade 4 hematologic toxicity was greater in irradiated patients (60% and 39%; P < .001). Patients given consolidation chemotherapy experienced superior median (21.1 v 13.2 months; P = .028) and 2-year survival (44% v 26%; P = .028) rates.


CONCLUSIONS
The concurrent use of TRT and CAV chemotherapy as administered in this study failed to improve the survival of limited-stage SCLC patients compared with CAV alone. Life-threatening hematologic toxicities were more frequent with combined-modality therapy. The survival of limited-stage patients treated with CAV (with or without TRT) was improved with two cycles of cisplatin and etoposide consolidation therapy. Whether similar survival results could be achieved with cisplatin and etoposide alone requires additional study.
Vanderbilt University School of Medicine, Nashville, TN 37232-5536.
D H
DH
Johnson
D
D
Bass
L H
LH
Einhorn
J
J
Crawford
C A
CA
Perez
A
A
Bartolucci
G A
GA
Omura
F A
FA
Greco
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011878:Radiotherapy / Q000379:methods; D016019:Survival Analysis; D013909:Thorax / Q000528:radiation effects; D017211:Treatment Failure; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin