PMID- 21841501
OWN - NLM
STAT- MEDLINE
DCOM- 20120209
LR  - 20131121
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 6
IP  - 11
DP  - 2011 Nov
TI  - Pralatrexate with vitamin supplementation in patients with previously treated, 
      advanced non-small cell lung cancer: safety and efficacy in a phase 1 trial.
PG  - 1915-22
LID - 10.1097/JTO.0b013e31822adb19 [doi]
AB  - 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(2) 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(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.
FAU - Azzoli, Christopher G
AU  - Azzoli CG
AD  - Memorial Sloan Kettering Cancer Center, New York City, New York, USA. 
      azzolic@mskcc.org
FAU - Patel, Jyoti D
AU  - Patel JD
FAU - Krug, Lee M
AU  - Krug LM
FAU - Miller, Vincent
AU  - Miller V
FAU - James, Leonard
AU  - James L
FAU - Kris, Mark G
AU  - Kris MG
FAU - Ginsberg, Michelle
AU  - Ginsberg M
FAU - Subzwari, Sara
AU  - Subzwari S
FAU - Tyson, Leslie
AU  - Tyson L
FAU - Dunne, Megan
AU  - Dunne M
FAU - May, Jennifer
AU  - May J
FAU - Huntington, Martha
AU  - Huntington M
FAU - Saunders, Michael
AU  - Saunders M
FAU - Sirotnak, F M
AU  - Sirotnak FM
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (10-propargyl-10-deazaaminopterin)
RN  - 0 (Folic Acid Antagonists)
RN  - 12001-76-2 (Vitamin B Complex)
RN  - 935E97BOY8 (Folic Acid)
RN  - JYB41CTM2Q (Aminopterin)
RN  - P6YC3EG204 (Vitamin B 12)
SB  - IM
MH  - Adenocarcinoma/*drug therapy/mortality/pathology
MH  - Aged
MH  - Aminopterin/*analogs & derivatives/pharmacokinetics/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality/pathology
MH  - Carcinoma, Squamous Cell/*drug therapy/mortality/pathology
MH  - *Dietary Supplements
MH  - Female
MH  - Folic Acid/administration & dosage
MH  - Folic Acid Antagonists/pharmacokinetics/therapeutic use
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/mortality/pathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Prognosis
MH  - Tissue Distribution
MH  - Vitamin B 12/administration & dosage
MH  - Vitamin B Complex/*administration & dosage
EDAT- 2011/08/16 06:00
MHDA- 2012/02/10 06:00
CRDT- 2011/08/16 06:00
PHST- 2011/08/16 06:00 [entrez]
PHST- 2011/08/16 06:00 [pubmed]
PHST- 2012/02/10 06:00 [medline]
AID - S1556-0864(15)32256-5 [pii]
AID - 10.1097/JTO.0b013e31822adb19 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2011 Nov;6(11):1915-22. doi: 10.1097/JTO.0b013e31822adb19.