Phase 1/2 dose escalating study of twice-monthly pemetrexed and gemcitabine in patients with advanced cancer and non-small cell lung cancer.
BACKGROUND
Pemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study.


METHODS
The phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis.


RESULTS
Maximum tolerated dose was gemcitabine 1500 mg/m, followed by pemetrexed 500 mg/m. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108-0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79-6.18), median survival was 10.1 month (95% CI: 5.95-14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%).


CONCLUSIONS
Twice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients.
Dudek
Arkadiusz Z
AZ
University of Minnesota Comprehensive Cancer Center, Minneapolis, Minnesota 55455, USA. dudek002@umn.edu
Larson
Timothy
T
McCleod
Michael J
MJ
Schneider
Daniel J
DJ
Dowell
Jonathan E
JE
Banerjee
Tarit K
TK
Pandya
Kishan J
KJ
Bromund
Jane L
JL
Chen
Ruqin
R
Monberg
Matthew J
MJ
Obasaju
Coleman K
CK
D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine