Phase II trial of pralatrexate (10-propargyl-10-deazaaminopterin, PDX) in patients with unresectable malignant pleural mesothelioma Journal Article
| Authors: | Krug, L. M.; Heelan, R. T.; Kris, M. G.; Venkatraman, E.; Sirotnak, F. M. |
| Article Title: | Phase II trial of pralatrexate (10-propargyl-10-deazaaminopterin, PDX) in patients with unresectable malignant pleural mesothelioma |
| Abstract: | 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/m IV 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. © 2007International Association for the Study of Lung Cancer. |
| Keywords: | survival; adult; cancer survival; clinical article; controlled study; treatment response; aged; aged, 80 and over; middle aged; survival analysis; unclassified drug; clinical trial; fatigue; mortality; cancer growth; dose response; drug efficacy; gemcitabine; cancer staging; antineoplastic agent; neoplasm staging; palliative care; carboplatin; controlled clinical trial; phase 2 clinical trial; anemia; nausea; stomatitis; vomiting; drug administration schedule; palliative therapy; terminally ill patient; pathology; dose-response relationship, drug; histology; risk assessment; lymphocytopenia; confidence interval; confidence intervals; survival time; terminally ill; probability; drug derivative; pleura mesothelioma; mesothelioma; malignant neoplastic disease; pleura tumor; folic acid; maximum tolerated dose; drug administration; dry eye; alopecia; epistaxis; pleural neoplasms; pralatrexate; aminopterin; cyanocobalamin; penis disease; antifolate; 10-propargyl-10-deazaaminopterin; or pdx; 10 propargyl 10 deazaaminopterin; penis ulcer |
| Journal Title: | Journal of Thoracic Oncology |
| Volume: | 2 |
| Issue: | 4 |
| ISSN: | 1556-0864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2007-04-01 |
| Start Page: | 317 |
| End Page: | 320 |
| Language: | English |
| DOI: | 10.1097/01.JTO.0000263715.84567.5f |
| PUBMED: | 17409804 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "Source: Scopus" |
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