Gemcitabine combined with either pemetrexed or paclitaxel in the treatment of advanced non-small cell lung cancer: a randomized phase II SICOG trial.
OBJECTIVE
To estimate the safety, activity, and impact on quality of life of a combination of gemcitabine and pemetrexed in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in the context of a randomized two-stage phase II study.


METHODS
Patients in stage IIIB or IV NSCLC were randomly allocated to receive either gemcitabine 1250 mg/m(2) on day 1, and pemetrexed (Alimta) 500 mg/m(2) followed by gemcitabine 1250 mg/m(2) on day 8 of a 3-weekly cycle (GA arm), or paclitaxel 120 mg/m(2) followed by gemcitabine 1000 mg/m(2), both given on days 1 and 8 of a 3-weekly cycle (PG arm).


RESULTS
105 (GA arm, 51; PG arm, 54) eligible patients (stage IV, 32 and 30, respectively) were enrolled into this study; thereafter, accrual was stopped due to first-stage analysis. The response rate was 20% (95% confidence interval [CI], 10-33%) in the GA arm, and 32% (95% CI, 20-46%) in the PG arm. Median progression-free survival was 5.1 (95% CI, 3.7-6.5) months in the GA arm, and 8.3 (95% CI, 5.9-10.7) months in the PG arm, while median overall survival was 10.5 (95% CI 7.1-13.9), and 13.3 (95% CI 11.7-14.9) months, respectively. Severe neutropenia (36% vs 22%), and febrile neutropenia (14% vs 7%) were more common with the GA regimen, while hair loss (52% vs 16%) and any grade peripheral neuropathy (31% vs 2%) occurred more frequently with PG regimen. Other severe side effects of GA regimen were diarrhoea (10%), liver enzyme derangement (10%), and fatigue (8%).


CONCLUSIONS
The GA regimen was tolerated and moderately active in advanced or metastatic NSCLC. However, this combination did not yield any advantage in comparison with the PG regimen, and does not deserve further evaluation.
Comella
Pasquale
P
National Tumour Institute, Via Semmola, 80131 Naples, Italy. pasqualecomella@libero.it
Chiuri
Vincenzo E
VE
De Cataldis
Giuseppe
G
Filippelli
Gianfranco
G
Maiorino
Luigi
L
Vessia
Giacomo
G
Cioffi
Riccardo
R
Mancarella
Sergio
S
Putzu
Carlo
C
Greco
Ettore
E
Palmeri
Laura
L
Costanzo
Raffaele
R
Avallone
Antonio
A
Franco
Luca
L
D000328:Adult; D000368:Aged; D000505:Alopecia / Q000209:etiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D000068437:Pemetrexed; D010523:Peripheral Nervous System Diseases / Q000209:etiology; D016019:Survival Analysis; D000093542:Gemcitabine
D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D017239:Paclitaxel; D000093542:Gemcitabine