Abstract | BACKGROUND: PROCEDURE: Patients (3-21 years) with NF1-related progressive PN received pirfenidone at the previously determined optimal dose (500 mg/m(2) orally, q8h) on a continuous dosing schedule (one cycle = 28 days). Volumetric MRI analysis was used to assess response. Progression was defined as ≥ 20% PN volume increase compared to baseline. Pirfenidone would be considered active if it doubled the median time to progression ( TTP) compared to the TTP on the placebo arm of a phase II trial with the farnesyltransferase inhibitor tipifarnib, which used near identical eligibility criteria. Toxicities, objective response rate, and quality of life (QOL) also were evaluated. RESULTS: Thirty-six patients were enrolled and tolerated pirfenidone well with intermittent nausea and vomiting as the most frequent toxicities. A dose reduction was required in only three patients. The median TTP for pirfenidone was 13.2 months compared to 10.6 months for the placebo control group from the tipifarnib trial (two-tailed P = 0.92; one-tailed P = 0.46). No objective responses were observed. CONCLUSIONS:
Pirfenidone was well tolerated, but did not demonstrate activity as defined in this trial and does not warrant further evaluation in children with NF1 and progressive PN.
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Authors | Brigitte C Widemann, Dusica Babovic-Vuksanovic, Eva Dombi, Pamela L Wolters, Stewart Goldman, Staci Martin, Anne Goodwin, Wendy Goodspeed, Mark W Kieran, Bruce Cohen, Susan M Blaney, Allison King, Jeffrey Solomon, Nicholas Patronas, Frank M Balis, Elizabeth Fox, Seth M Steinberg, Roger J Packer |
Journal | Pediatric blood & cancer
(Pediatr Blood Cancer)
Vol. 61
Issue 9
Pg. 1598-602
(Sep 2014)
ISSN: 1545-5017 [Electronic] United States |
PMID | 24753394
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Copyright | © 2014 Wiley Periodicals, Inc. |
Chemical References |
- Antineoplastic Agents
- Pyridones
- Tumor Necrosis Factor-alpha
- pirfenidone
|
Topics |
- Adolescent
- Adult
- Antineoplastic Agents
(therapeutic use)
- Child
- Child, Preschool
- Disease Progression
- Female
- Follow-Up Studies
- Humans
- Male
- Neoplasm Staging
- Neurofibroma, Plexiform
(drug therapy, mortality, pathology)
- Neurofibromatosis 1
(drug therapy, mortality, pathology)
- Prognosis
- Pyridones
(therapeutic use)
- Quality of Life
- Survival Rate
- Time Factors
- Tumor Necrosis Factor-alpha
(antagonists & inhibitors)
- Young Adult
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