Pralatrexate with vitamin supplementation in patients with previously treated, advanced non-small cell lung cancer: Safety and efficacy in a phase 1 trial

Christopher G. Azzoli*, Jyoti D. Patel, Lee M. Krug, Vincent Miller, Leonard James, Mark G. Kris, Michelle Ginsberg, Sara Subzwari, Leslie Tyson, Megan Dunne, Jennifer May, Martha Huntington, Michael Saunders, F. M. Sirotnak

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Introduction: Pralatrexate is an antifolate designed for preferential tumor cell uptake and accumulation and received accelerated Food and Drug Administration approval in relapsed/refractory peripheral T-cell lymphoma. Pralatrexate 135 to 150 mg/m every 2 weeks without vitamin supplementation was active in non-small cell lung cancer (NSCLC) although mucositis was dose limiting. This phase 1 study evaluated the safety of higher pralatrexate doses with vitamin supplementation to minimize toxicities. Methods: Patients with stage IIIB/IV NSCLC received pralatrexate 150 to 325 mg/m every 2 weeks with folic acid and vitamin B12 supplementation. Outcomes measured included adverse events (AEs), pharmacokinetics, and radiologic response. Results: Thirty-nine patients were treated for a median of two cycles (range 1-16+). Common treatment-related grade 3 and 4 AEs by dose (≤190 mg/m and >190 mg/m) included mucositis (33 and 40%) and fatigue (11 and 17%). Treatment-related serious AE (SAE) rates for doses ≤190 and >190 mg/m were 0 and 20%, respectively. The response rate was 10% (95% confidence interval: 1-20%), including two patients with complete response (26+ and 32+ months) and two with partial response. Serum pralatrexate concentrations increased dose dependently up to 230 mg/m. Conclusions: Pralatrexate with vitamin supplementation was safely administered to patients with previously treated NSCLC, and durable responses were observed. The recommended starting dose for phase 2 is 190 mg/m. A similar safety profile was observed in patients treated at 230 mg/m, although a higher serious AE rate was evident. Mucositis remains the dose-limiting toxicity of pralatrexate, and this study failed to demonstrate that vitamin supplementation prevents mucositis and failed to identify clinical predictors of mucositis. Individualized dose-modification strategies and prospective mucositis management will be necessary in future trials.

Original languageEnglish (US)
Pages (from-to)1915-1922
Number of pages8
JournalJournal of Thoracic Oncology
Issue number11
StatePublished - Nov 2011


  • Antifolate
  • Dose-finding
  • Non-small cell lung cancer
  • Pralatrexate

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine


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