A phase 1 study of pralatrexate in combination with paclitaxel or docetaxel in patients with advanced solid tumors Journal Article


Authors: Azzoli, C. G.; Krug, L. M.; Gomez, J.; Miller, V. A.; Kris, M. G.; Ginsberg, M. S.; Henry, R.; Jones, J.; Tyson, L.; Dunne, M.; Pizzo, B.; Farmer, A.; Venkatraman, E.; Steffen, R.; Sirotnak, F. M.
Article Title: A phase 1 study of pralatrexate in combination with paclitaxel or docetaxel in patients with advanced solid tumors
Abstract: Purpose: Pralatrexate is a rationally designed antifolate with greater preclinical antitumor activity than methotrexate. Pralatrexate was synergistic with paclitaxel and with docetaxel in mouse xenograft experiments. This phase 1 study was designed to determine the maximum tolerated dose and toxicity of pralatrexate plus paclitaxel or docetaxel in patients with advanced cancer. Experimental Design: Pralatrexate was administered i.v. every 2 weeks (days 1 and 15) in a 4-week cycle. Depending on the taxane used and dose being tested, the taxane was administered on days 1 and 15; days 2 and 16; or days 1, 8, and 15. In the latter part of the study, patients in the docetaxel arm were treated with vitamin B12 and folic acid supplementation to mitigate toxicity and allow pralatrexate dose escalation. Results: For the combination of pralatrexate plus paclitaxel without vitamin supplementation, dose-limiting stomatitis and peripheral neuropathy were encountered at the lowest dose levels tested. For pralatrexate plus docetaxel plus vitamin supplementation, pralatrexate 120 mg/m2 plus docetaxel 35 mg/m2 administered on the same day every other week was defined as the maximum tolerated dose and schedule, with dose-limiting toxicities at higher dose combinations including stomatitis and asthenia. Significant antitumor activity was observed for this combination in patients with non - small-cell lung cancer. Conclusions: Pralatrexate (120 mg/m2) plus docetaxel (35 mg/m 2) plus vitamin supplementation is well tolerated with signs of efficacy against non - small-cell lung cancer that merit phase 2 testing. © 2007 American Association for Cancer Research.
Keywords: adult; cancer survival; clinical article; controlled study; treatment response; aged; middle aged; unclassified drug; clinical trial; drug tolerability; fatigue; neutropenia; diarrhea; drug efficacy; solid tumor; paclitaxel; neoplasms; controlled clinical trial; multiple cycle treatment; anemia; nausea; neuropathy; stomatitis; thrombocytopenia; antineoplastic combined chemotherapy protocols; peripheral neuropathy; antineoplastic activity; docetaxel; asthenia; drug dose escalation; peripheral edema; vitamin supplementation; taxoids; dietary supplements; folic acid; homocysteine; phase 1 clinical trial; folic acid antagonists; alopecia; pralatrexate; aminopterin; cyanocobalamin; methylmalonic acid; 10 deazaaminopterin; vitamins
Journal Title: Clinical Cancer Research
Volume: 13
Issue: 9
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2007-05-01
Start Page: 2692
End Page: 2698
Language: English
DOI: 10.1158/1078-0432.ccr-06-1754
PUBMED: 17473201
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 17" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Venkatraman Ennapadam Seshan
    282 Seshan
  2. Jorge Gomez
    25 Gomez
  3. Michelle S Ginsberg
    154 Ginsberg
  4. Lee M Krug
    202 Krug
  5. Christopher G Azzoli
    99 Azzoli
  6. Vincent Miller
    251 Miller
  7. Megan Dunne
    17 Dunne
  8. Mark Kris
    581 Kris
  9. Francis M Sirotnak
    112 Sirotnak
  10. Leslie Tyson
    49 Tyson
  11. Barbara Pizzo
    31 Pizzo
  12. Roxanne Henry
    5 Henry
  13. Jessica M Jones
    7 Jones