Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy.
OBJECTIVE
To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy.


METHODS
Eligible patients had a performance status 0 to 2, previous treatment with one prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Patients received pemetrexed 500 mg/m(2) intravenously (i.v.) day 1 with vitamin B(12), folic acid, and dexamethasone or docetaxel 75 mg/m(2) i.v. day 1 with dexamethasone every 21 days. The primary end point was overall survival.


RESULTS
Five hundred seventy-one patients were randomly assigned. Overall response rates were 9.1% and 8.8% (analysis of variance P =.105) for pemetrexed and docetaxel, respectively. Median progression-free survival was 2.9 months for each arm, and median survival time was 8.3 versus 7.9 months (P = not significant) for pemetrexed and docetaxel, respectively. The 1-year survival rate for each arm was 29.7%. Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia (40.2% v 5.3%; P <.001), febrile neutropenia (12.7% v 1.9%; P <.001), neutropenia with infections (3.3% v 0.0%; P =.004), hospitalizations for neutropenic fever (13.4% v 1.5%; P <.001), hospitalizations due to other drug related adverse events (10.5% v 6.4%; P =.092), use of granulocyte colony-stimulating factor support (19.2% v 2.6%, P <.001) and all grade alopecia (37.7% v 6.4%; P <.001) compared with patients receiving pemetrexed.


CONCLUSIONS
Treatment with pemetrexed resulted in clinically equivalent efficacy outcomes, but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a standard treatment option for second-line NSCLC when available.
Hanna
Nasser
N
Indiana University, 535 Barnhill Dr, Room 473, Indianapolis, IN 46202, USA. nhanna@iupui.edu
Shepherd
Frances A
FA
Fossella
Frank V
FV
Pereira
Jose R
JR
De Marinis
Filippo
F
von Pawel
Joachim
J
Gatzemeier
Ulrich
U
Tsao
Thomas Chang Yao
TC
Pless
Miklos
M
Muller
Thomas
T
Lim
Hong-Liang
HL
Desch
Christopher
C
Szondy
Klara
K
Gervais
Radj
R
Shaharyar
Manegold
Christian
C
Paul
Sofia
S
Paoletti
Paolo
P
Einhorn
Lawrence
L
Bunn
Paul A
PA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D000068437:Pemetrexed; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D006147:Guanine