Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902.
OBJECTIVE
We initially conducted a randomized phase II study to compare irinotecan and cisplatin (IP) versus irinotecan, cisplatin, and etoposide (IPE) after etoposide and cisplatin (EP) with concurrent twice-daily thoracic radiotherapy (TRT) in limited-disease small-cell lung cancer (LD-SCLC). We amended the protocol to evaluate IP after EP with concurrent twice-daily TRT in a single-arm phase II study because of an unacceptable toxicity in IPE.


METHODS
Previously untreated patients with LD-SCLC were treated intravenously with etoposide 100 mg/m2 on days 1 through 3 and cisplatin 80 mg/m2 on day 1 with concurrent twice-daily TRT (1.5 Gy per fraction, a total dose of 45 Gy) beginning on day 2 followed by three cycles of irinotecan 60 mg/m2 on days 1, 8, and 15 and cisplatin 60 mg/m2 on day 1 of a 4-week cycle.


RESULTS
Of the 51 patients enrolled, 49 patients were assessable for response and toxicity. The overall response rate and complete response rate were 88% and 41%, respectively. The median survival time for all patients was 23 months. The 2-year and 3-year survival rates were 49% and 29.7%, respectively. The median progression-free survival was 11.8 months. The major toxicities observed were neutropenia (grade 4, 84%), febrile neutropenia (grade 3, 31%), infection (grade 3 to 4, 33%), electrolytes imbalance (grade 3 to 4, 20%), and diarrhea (grade 3 to 4, 14%).


CONCLUSIONS
EP with concurrent twice-daily TRT followed by the consolidation of IP appears to be an active regimen which deserves further phase III testing in patients with LD-SCLC.
Saito
Hiroshi
H
Department of Respiratory Medicine, Aichi Cancer Center Aichi Hospital, Okazaki Aichi, Japan. hsaito@sun-inet.or.jp
Takada
Yoshiki
Y
Ichinose
Yukito
Y
Eguchi
Kenji
K
Kudoh
Shinzoh
S
Matsui
Kaoru
K
Nakagawa
Kazuhiko
K
Takada
Minoru
M
Negoro
Shunichi
S
Tamura
Kenji
K
Ando
Masahiko
M
Tada
Takuhito
T
Fukuoka
Masahiro
M
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D003967:Diarrhea / Q000209:etiology; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D007239:Infections / Q000209:etiology; D000077146:Irinotecan; D007564:Japan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
D005047:Etoposide; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin