Superiority of high-dose platinum (cisplatin and carboplatin) compared to carboplatin alone in combination chemotherapy for small-cell lung carcinoma: a prospective randomised trial of 280 consecutive patients.
OBJECTIVE
A prospective randomized trial in small-cell lung cancer (SCLC) was performed to determine if intensification of the platinum dose by giving cisplatin and carboplatin in combination to patients with SCLC yields higher response rates and survival, than carboplatin alone in a combination chemotherapy regimen.


METHODS
Between September 1992 and October 1997, 280 patients were included in a two armed prospective randomized trial, stratified by stage of disease, LDH and performance status. The treatment was in arm A: three courses induction chemotherapy with carboplatin (AUC = 4, day 1), cisplatin (35 mg/m2, days 2 and 3), teniposide (50 mg/m2, day 1-5), vincristine (1.3 mg/m2, day 1) every four weeks, followed by cyclophosphamide (3 g/m2, day 84), 4-epirubicin (4-epidoxorubicin) (150 mg/m2, day 112), and finally one course cisplatin, carboplatin, teniposide and vincristine, (days 140-144). Arm B also comprised a total of six courses, identical to those in arm A except for omission of cisplatin.


RESULTS
There were no significant differences in the overall treatment outcome for A vs. B, in terms of response rates (72% in both arms), complete response rates (40% and 34%, respectively), or median survival (314 days and 294 days, respectively). However, for patients with limited disease both the CR rate (54% vs. 37%, P < 0.05), overall survival (log-rank test, P < 0.05), and the two-year survival rate (11% vs. 6%, P < 0.05) were higher in the high-dose platinum arm compared to the carboplatin alone arm.


CONCLUSIONS
The intensification of platinum dose (cisplatin plus carboplatin) in combination chemotherapy significantly increased the complete response rate, overall survival and number of two-year survivors among SCLC patients with limited disease compared to combination therapy with carboplatin alone, suggesting that a more aggressive treatment to this category of patients is worthwhile, while no difference in treatment outcome was observed for patients with extensive disease.
Hirsch
F R
FR
Rigshospitalet, Finsen Center, Department of Oncology, Denmark. Fred.Hirsch@UCHSC.edu
Osterlind
K
K
Jeppesen
N
N
Dombernowsky
P
P
Ingeberg
S
S
Sorensen
P G
PG
Kristensen
C
C
Hansen
H H
HH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D013713:Teniposide / Q000008:administration & dosage; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D015251:Epirubicin; D014750:Vincristine; D003520:Cyclophosphamide; D013713:Teniposide; D016190:Carboplatin; D015080:Mesna; D002945:Cisplatin