Feasibility study of dose-dense biweekly administered pemetrexed in patients with non-small cell lung cancer.
OBJECTIVE
Pemetrexed is a multitargeted folate pathway inhibitor with documented activity in non-small cell lung cancer (NSCLC). The presumed maximum tolerated dose is 500 mg/m2 every 3 weeks, but pemetrexed-related toxicity is ameliorated when folate and B12 supplementation is provided and therefore a higher dose intensity may be tolerated. The current exploratory study assessed the feasibility of administration of pemetrexed at a fixed dose of 1000 mg every 2 weeks in patients with relapsed or refractory NSCLC.


METHODS
The first cohort of 12 patients received pemetrexed monotherapy. No dose-limiting grade 4 toxicity was noted after 4 cycles, so the subsequent cohort of 14 patients received additional anticancer agents (bevacizumab, erlotinib, carboplatin, docetaxel, vinorelbine) given along with dose-dense pemetrexed.


RESULTS
Toxicity overall was reversible and manageable. Among 19 patients who received pemetrexed either alone or with non-myelosuppressive targeted agents, there were only 2 instances of grade 4 neutropenia after prolonged treatment. Grade 3-4 hematologic toxicity was eventually noted in 11 of the 26 patients (42%; 95% confidence interval, 23% to 61%) after a median of 4 cycles (range, 2-14 cycles). There was no significant additional toxicity nor any treatment-related deaths.


CONCLUSIONS
Our preliminary observations indicate that dose-dense pemetrexed every 2 weeks is feasible and this regimen can be used as monotherapy. These data may serve as a scaffold for combination studies.
Emmanouilides
Christos
C
Interbalkan Medical Center, Thessaloniki, Greece.
Yermetaki
Theodora
T
Serpanou
Anastasia
A
Sapountzi
Evdoxia
E
Mantziari
Polyxeni
P
Titopoulos
Iraklis
I
Filippou
Dimitrios
D
D000368:Aged; D000964:Antimetabolites, Antineoplastic; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005240:Feasibility Studies; D005260:Female; D005493:Folic Acid Antagonists; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D000068437:Pemetrexed; D014805:Vitamin B 12 / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D014805:Vitamin B 12