A phase III randomised study comparing two different dose-intensity regimens as induction chemotherapy followed by thoracic irradiation in patients with advanced locoregional non-small-cell lung cancer.
OBJECTIVE
The aim of this study was to determine the role of chemotherapy dose intensity in patients with initially unresectable non-metastatic non-small-cell lung cancer (NSCLC), with survival as primary end point, by testing two different regimens as induction chemotherapy followed by thoracic irradiation.


METHODS
Patients had pathologically proven NSCLC, an initially unresectable non-metastatic tumour without homolateral malignant pleural effusion, no prior history of malignancy and had received no prior therapy. Treatment was randomised for chemotherapy between three courses of MIP (mitomycin C 6 mg/m2; ifosfamide 3 g/m2; cisplatin 50 mg/m2) or SuperMIP (mitomycin C 6 mg/m2; ifosfamide 4.5 g/m2; cisplatin 60 mg/m2, carboplatine 200 mg/m2), followed by chest irradiation (60 Gy; five times per week, for 6 weeks). If the tumour became resectable after chemotherapy, surgery was performed, followed by mediastinal irradiation.


RESULTS
A total of 351 patients were eligible: 176 in the MIP arm and 175 in the SuperMIP arm, with 43% and 51% stages IIIA and IIIB, respectively. There was a significantly higher objective response rate with SuperMIP (46%) compared with MIP (35%) (P=0.03) [95% confidence interval (CI) for the difference between the response rates, 1% to 22%]. After induction chemotherapy, surgery was performed in 54 (15%) patients (27 per arm) and chest irradiation in 203 (57%) patients (102 in the MIP arm and 101 in the SuperMIP). In terms of survival, there was no statistically significant difference between the two study arms (P=0.16), with median survival times of, for MIP and SuperMIP, respectively, 12.5 (95% CI 10.1-14.9) and 11.2 (95% CI 9.7-12.8) months. Haematological toxicity and dosage reductions were higher with SuperMIP, which was nevertheless associated with a significantly increased absolute dose intensity.


CONCLUSIONS
High dose-intensity induction chemotherapy does not improve survival in initially unresectable non metastatic NSCLC.
Sculier
J-P
JP
Institut Jules Bordet, Brussels, Belgium. sculier@bordet.be
Lafitte
J-J
JJ
Berghmans
T
T
Van Houtte
P
P
Lecomte
J
J
Thiriaux
J
J
Efremidis
A
A
Koumakis
G
G
Giner
V
V
Richez
M
M
Corhay
J-L
JL
Wackenier
P
P
Lothaire
P
P
Paesmans
M
M
Mommen
P
P
Ninane
V
V
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage*; D009367:Neoplasm Staging; D012074:Remission Induction; D015996:Survival Rate; D013909:Thorax / Q000528:radiation effects*; D016896:Treatment Outcome
D016685:Mitomycin; D002945:Cisplatin; D007069:Ifosfamide