Abstract | INTRODUCTION: METHODS: Patients with stage IIIB/IV NSCLC received pralatrexate 150 to 325 mg/m(2) 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(2) and >190 mg/m(2)) included mucositis (33 and 40%) and fatigue (11 and 17%). Treatment-related serious AE (SAE) rates for doses ≤190 and >190 mg/m(2) 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(2). 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(2). A similar safety profile was observed in patients treated at 230 mg/m(2), 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.
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Authors | 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 |
Journal | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
(J Thorac Oncol)
Vol. 6
Issue 11
Pg. 1915-22
(Nov 2011)
ISSN: 1556-1380 [Electronic] United States |
PMID | 21841501
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- 10-propargyl-10-deazaaminopterin
- Folic Acid Antagonists
- Vitamin B Complex
- Folic Acid
- Aminopterin
- Vitamin B 12
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Topics |
- Adenocarcinoma
(drug therapy, mortality, pathology)
- Aged
- Aminopterin
(analogs & derivatives, pharmacokinetics, therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
- Carcinoma, Non-Small-Cell Lung
(drug therapy, mortality, pathology)
- Carcinoma, Squamous Cell
(drug therapy, mortality, pathology)
- Dietary Supplements
- Female
- Folic Acid
(administration & dosage)
- Folic Acid Antagonists
(pharmacokinetics, therapeutic use)
- Humans
- Lung Neoplasms
(drug therapy, mortality, pathology)
- Male
- Maximum Tolerated Dose
- Middle Aged
- Prognosis
- Tissue Distribution
- Vitamin B 12
(administration & dosage)
- Vitamin B Complex
(administration & dosage)
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