Phase II study of pemetrexed with and without folic acid and vitamin B12 as front-line therapy in malignant pleural mesothelioma.
OBJECTIVE
This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma (MPM).


METHODS
Patients with a histologically proven diagnosis of MPM, chemotherapy-naive measurable lesions, and adequate organ function received pemetrexed (500 mg/m2) intravenously over 10 minutes every 3 weeks. After a protocol change, most patients also received folic acid and vitamin B12 supplementation to improve safety.


RESULTS
A total of 64 patients were enrolled. Nine (14.1%) of the 64 patients had a partial response. The Kaplan-Meier estimate for median overall survival was 10.7 months. Forty-three patients received vitamin supplementation for all courses of therapy, and 21 patients did not. Seven of the nine responders were vitamin supplemented. The median overall survival was 13.0 months for supplemented patients and 8.0 months for nonsupplemented patients. Vitamin-supplemented patients completed more cycles of therapy than nonsupplemented patients (median, six v two cycles, respectively). Grade 3/4 neutropenia (23.4%) and grade 3/4 leukopenia (18.8%) were the most common laboratory toxicities. Fatigue and febrile neutropenia were the most commonly reported nonlaboratory events (grade 3, 6.3%; grade 4, 0.0% each). The incidence of these toxicities was generally lower in the supplemented patients.


CONCLUSIONS
Single-agent pemetrexed for MPM resulted in a moderate response rate (14.1%) and median overall survival of 10.7 months. Patients supplemented with folic acid and vitamin B12 tolerated treatment better (less toxicity and more cycles of treatment) and had a 5-month greater median overall survival than nonsupplemented patients. These results indicate that patients with MPM could benefit from single-agent pemetrexed treatment combined with vitamin supplementation.
Scagliotti
Giorgio V
GV
University of Turin, Department of Clinical and Biological Sciences, Azienda Ospedaliera S. Luigi, Regione Gonzole 10, 10043 Orbassano (Torino) Italy. scagliotti@ihnet.it
Shin
Dong-M
DM
Kindler
Hedy L
HL
Vasconcelles
Michael J
MJ
Keppler
Uwe
U
Manegold
Christian
C
Burris
Howard
H
Gatzemeier
Ulrich
U
Blatter
Johannes
J
Symanowski
James T
JT
Rusthoven
James J
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005493:Folic Acid Antagonists / Q000627:therapeutic use; D005500:Follow-Up Studies; D005971:Glutamates / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006397:Hematinics / Q000008:administration & dosage*; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy*; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D005971:Glutamates; D006397:Hematinics; D000068437:Pemetrexed; D006147:Guanine; D005492:Folic Acid