Pemetrexed plus cetuximab in patients with recurrent non-small cell lung cancer (NSCLC): a phase I/II study from the Hoosier Oncology Group.
OBJECTIVE
Pemetrexed is a standard treatment against recurrent non-small cell lung cancer (NSCLC), and cetuximab has single-agent activity against NSCLC. This study evaluates the safety and efficacy of the combination of these agents in patients with advanced NSCLC.


METHODS
Patients with recurrent NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1 were entered. Patients on the phase I portion of the study received cetuximab 400 mg/m2 intravenously (IV) on day -7 followed by weekly doses of cetuximab at 250 mg/m2 IV with escalating doses of pemetrexed every 3 weeks (dose levels: 500, 600, 750, 900 mg/m2) in a standard 3 + 3 design. Once the maximum tolerated dose (MTD) of the combination was determined, patients were enrolled on the phase II portion. The primary end point was to determine the median time to disease progression (TTP) (null hypothesis 12 weeks, alternative hypothesis 24 weeks).


RESULTS
Thirty-six patients were enrolled (phase I: n = 13, phase II: n = 23). Patient characteristics included 60.6% men, median age 64 years (range, 37-80 years), 57.6% had performance status 0 and 54.6% had adenocarcinoma histology. The median number of previous regimens was 2 (range, 1-6). The maximum tolerated dose of pemetrexed in combination with cetuximab was determined to be 750 mg/m2. The median TTP was 14.6 weeks. The median survival time was 42 weeks and 1-year survival was 38.5%.


CONCLUSIONS
The combination of pemetrexed at 750 mg/m2 every 21 days with weekly cetuximab at 250 mg/m2 was feasible; however, in this unselected patient population, the combination regimen does not seem to improve TTP compared with historical controls of either single agent.
Jalal
Shadia
S
Indiana University Simon Cancer Center, Indianapolis, Indiana 46202, USA. sjalal@iupui.edu
Waterhouse
David
D
Edelman
Martin J
MJ
Nattam
Sreenivasa
S
Ansari
Rafat
R
Koneru
Karuna
K
Clark
Romnee
R
Richards
Arthur
A
Wu
Jingwei
J
Yu
Menggang
M
Bottema
Brian
B
White
Angela
A
Hanna
Nasser
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000068818:Cetuximab; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D066246:ErbB Receptors; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D000068437:Pemetrexed; D012189:Retrospective Studies; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase; D066246:ErbB Receptors; D000068818:Cetuximab