Phase II trial of pralatrexate (10-propargyl-10-deazaaminopterin, PDX) in patients with unresectable malignant pleural mesothelioma.
BACKGROUND
Several previous clinical trials have shown that malignant pleural mesothelioma is responsive to antifolates. The dihydrofolate reductase inhibitor, pralatrexate, has a favorable toxicity profile, primarily limited to stomatitis, and has demonstrated activity in patients with non-small cell lung cancer. In mesothelioma cell lines and xenografts, pralatrexate demonstrated significant antitumor activity.


METHODS
We conducted this phase II study to determine the response rate of malignant pleural mesothelioma to pralatrexate at a dose of 135 mg/m2 i.v. every 2 weeks. After a protocol amendment, patients were supplemented with vitamin B12 and folic acid at the time of starting therapy.


RESULTS
A total of 16 assessable patients were enrolled. No complete or partial responses were observed. Two patients with epithelioid histology had minor responses. Three other patients remained on study with stable disease for 9, 9, and 48 months. The median time to progression was 3 months. The overall median survival time was 7 months (95% confidence interval: 3.2-16.2 months) and the one-year survival was 31% (95% confidence interval: 15%-65%). Three patients (19%) had grade 2 stomatitis, eight (50%) had grade 3, and one (6%) had grade 4.


CONCLUSIONS
With this particular dose and schedule, pralatrexate as a single agent had no activity in malignant pleural mesothelioma.
Krug
Lee M
LM
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10021, USA. krugl@mskcc.org
Heelan
Robert T
RT
Kris
Mark G
MG
Venkatraman
Ennapadam
E
Sirotnak
F M
FM
D000368:Aged; D000369:Aged, 80 and over; D000630:Aminopterin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D010166:Palliative Care; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis; D019452:Terminally Ill
C418863:10-propargyl-10-deazaaminopterin; D000630:Aminopterin