Phase II study of biweekly pemetrexed and gemcitabine in patients with previously untreated advanced non-small cell lung cancer.
BACKGROUND
Pemetrexed and gemcitabine are safe and active non-small cell lung cancer (NSCLC) therapies when administered every 3 weeks. Biweekly scheduling was studied in this phase II trial.


METHODS
The primary objective was to assess the overall response rate in chemotherapy-naive patients with unresectable stage III/IV NSCLC. Patients received 500 mg/m(2) of pemetrexed intravenously and 1500 mg/m(2) of gemcitabine intravenously every 2 weeks for 8 to 12 cycles with restaging every 4 cycles. Patients also received supplemental folate/B12 therapy. Entry criteria included the following: all non-small cell histologies, measurable disease, Eastern Cooperative Oncology Group 0 to 2, and informed consent.


RESULTS
Seventy-two patients were enrolled. Baseline characteristics included the following: median age: 66 years (41-85 years); male/female: 65%/35%; Eastern Cooperative Oncology Group 0/1/2: 19%/67%/14%; and histology: adenocarcinoma (36%), large cell (18%), squamous (13%), and mixed or not specified (34%). The median number of cycles was 7 (range, 1-12). The most common (> or =5%) grade 3/4 toxicities were as follows: neutropenia (47%), leukopenia (31%), fatigue (25%), dyspnea (18%), pain (11%), and anemia (8%). Complete/partial responses for all patients: 1 patient/18 patients, respectively, for an overall response rate of 26% (95% confidence interval, 17-38%). Thirty-nine percentage of patients had stable disease, and 21% had disease progression (10 patients were not evaluable). Median progression-free survival was 6.2 months. One-year overall survival was 37.5%.


CONCLUSIONS
Biweekly administration of pemetrexed and gemcitabine seems to be well tolerated with activity comparable with other first-line NSCLC regimens. Further study addressing whether biweekly scheduling could be an effective strategy to shorten overall treatment duration will require a randomized design.
Spigel
David R
DR
Sarah Cannon Research Institute, Nashville, Tennessee 37203, USA. dspigel@tnonc.com
Hainsworth
John D
JD
Barton
John H
JH
Patton
Jeffrey F
JF
Zubkus
John D
JD
Simons
Lisa
L
Griner
Paula
P
Burris
Howard A
HA
Greco
F Anthony
FA
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* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; 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; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D000093542:Gemcitabine
D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine