Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer.
OBJECTIVE
To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC).


METHODS
A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy.


RESULTS
Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033).


CONCLUSIONS
Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.
Depierre
Alain
A
Chest Disease Department, J. Minjoz University Hospital, 25030 Besançon Cedex, France. pneumo-depierre@ufc-chu.univ-fcomte.fr
Milleron
Bernard
B
Moro-Sibilot
Denis
D
Chevret
Sylvie
S
Quoix
Elisabeth
E
Lebeau
Bernard
B
Braun
Denis
D
Breton
Jean-Luc
JL
Lemarié
Etienne
E
Gouva
Sylvie
S
Paillot
Nadine
N
Bréchot
Jeanne-Marie
JM
Janicot
Henri
H
Lebas
François-Xavier
FX
Terrioux
Philippe
P
Clavier
Jean
J
Foucher
Pascal
P
Monchâtre
Michel
M
Coëtmeur
Daniel
D
Level
Marie-Claude
MC
Leclerc
Pascal
P
Blanchon
François
F
Rodier
Jean-Michel
JM
Thiberville
Luc
L
Villeneuve
Anne
A
Westeel
Virginie
V
Chastang
Claude
C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D011300:Preoperative Care; D016016:Proportional Hazards Models; D015996:Survival Rate
D016685:Mitomycin; D002945:Cisplatin; D007069:Ifosfamide