Cisplatin-based three drugs combination (NIP) as induction and adjuvant treatment in locally advanced non-small cell lung cancer: final results.
BACKGROUND
This phase III trial was conducted in non-small cell lung cancer patients with locally advanced stage II B (only T3N0) III A and III B (only T4 N0). Primary endpoint was 2-year survival; secondary were toxicity, disease-free survival, and overall survival.


METHODS
After three cycles of vinorelbine (N) 25 mg/m2 on days 1 and 5, ifosfamide/mesna (I) 3 g/m2 on day 1, cisplatin (P) (NIP), patients were treated by surgery and within 45 days were randomized to two additional cycles of NIP versus observation.


RESULTS
Median tumor diameter was 5.5 cm (1.2-10.6). Overall, 155 of 156 patients received chemotherapy: 133 (85%) men, median age: 59 years (35-75). Sixty-five percentage of patients were stage III A, 28% II B, and 7% III B. The study has been closed prematurely because of the low inclusion rate. After three cycles of induction in 143 assessable patients, 82 reported an objective response (57.3%) (95% CI: 48.8-65.6), with 3.5% complete response and 53.8% partial response. Relative dose intensity during neoadjuvant NIP (%) was 97, 98, and 98.5 for vinorelbine, ifosfamide/mesna, and cisplatin, respectively. Tolerance: G3 to 4 neutropenia in 3% of patients and G3 to 4 anemia in 4%; nonhematological toxicities included G3 nausea/vomiting in 11%, G3 anorexia and G3 to 4 infection in 6.5%, G3 asthenia in 10% and G3 to 4 alopecia in 25.5%. After a median of 32 days after NIP, 107 patients (69%) underwent operation with complete resection (R0) in 74% (79 of 107 patients). Downstaging (N2 to N0) after surgery was 29%. Operative mortality rate was 2.8%. Twenty-one days (median) after surgery, 79 patients were randomized to adjuvant NIP (47%) or control (53%). Tolerance of adjuvant NIP: 12.5% G3 to 4 nausea/vomiting, 19% G3 alopecia, 6% G3 infection, and G3 asthenia. Overall median survival 32.3 versus 31.8 months in the observation and NIP arms, respectively.


CONCLUSIONS
NIP allows 74% of R0 with no surgery delay. The few number of randomized patients did not allow to conclude on the efficacy of adjuvant chemotherapy.
Gottfried
Maya
M
Meir Medical Center, Kfar-Saba, Israel.
Ramlau
Rodryg
R
Krzakowski
Maciej
M
Ziolo
Grzegorz
G
Olechnowicz
Henryk
H
Koubkova
Leona
L
Dahabreh
Jubrail
J
Szczesna
Aleksandra
A
Vivanco
Guillermo Lopez
GL
Perng
Reury-Perng
RP
Carpagnano
Francesco
F
Leong
Swan-Swan
SS
Fittipaldo
Alberto
A
De Almeida
Cecilia
C
Aubert
Delphine
D
Grunenwald
Dominique
D
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D007069:Ifosfamide