Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma

A report from the children's oncology group

Judith G. Villablanca, Wendy B. London, Arlene Naranjo, Patrick McGrady, Matthew M. Ames, Joel M Reid, Renee M. McGovern, Sarah A. Buhrow, Hollie Jackson, Enno Stranzinger, Brenda J. Kitchen, Paul M. Sondel, Marguerite T. Parisi, Barry Shulkin, Gregory A. Yanik, Susan L. Cohn, C. Patrick Reynolds

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma. Experimental Design: Patients received 7 days of fenretinide: 2,475 mg/m 2/d divided TID (<18 years) or 1,800 mg/m 2/d divided BID (≥18 years) every 21 days for a maximum of 30 courses. Patients with stable or responding disease after course 30 could request additional compassionate courses. Best response by course 8 was evaluated in stratum 1 (measurable disease on CT/MRI ± bone marrow and/or MIBG avid sites) and stratum 2 (bone marrow and/or MIBG avid sites only). Results: Sixty-two eligible patients, median age 5 years (range 0.6-19.9), were treated in stratum 1 (n = 38) and stratum 2 (n = 24). One partial response (PR) was seen in stratum 2 (n = 24 evaluable). No responses were seen in stratum 1 (n=35 evaluable). Prolonged stable disease (SD) was seen in 7 patients in stratum 1 and 6 patients in stratum 2 for 4 to 45+ (median 15) courses. Median time to progression was 40 days (range 17-506) for stratum 1 and 48 days (range 17-892) for stratum 2. Mean 4-HPR steady-state trough plasma concentrations were 7.25 μmol/L (coefficient of variation 40-56%) at day 7 course 1. Toxicities were mild and reversible. Conclusions: Although neither stratum met protocol criteria for efficacy, 1 PR + 13 prolonged SD occurred in 14/59 (24%) of evaluable patients. Low bioavailability may have limited fenretinide activity. Novel fenretinide formulations with improved bioavailability are currently in pediatric phase I studies.

Original languageEnglish (US)
Pages (from-to)6858-6866
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number21
DOIs
StatePublished - Nov 1 2011

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Fenretinide
Neuroblastoma
Pediatrics
3-Iodobenzylguanidine
Biological Availability
Bone Marrow
Research Design
Biopsy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma : A report from the children's oncology group. / Villablanca, Judith G.; London, Wendy B.; Naranjo, Arlene; McGrady, Patrick; Ames, Matthew M.; Reid, Joel M; McGovern, Renee M.; Buhrow, Sarah A.; Jackson, Hollie; Stranzinger, Enno; Kitchen, Brenda J.; Sondel, Paul M.; Parisi, Marguerite T.; Shulkin, Barry; Yanik, Gregory A.; Cohn, Susan L.; Patrick Reynolds, C.

In: Clinical Cancer Research, Vol. 17, No. 21, 01.11.2011, p. 6858-6866.

Research output: Contribution to journalArticle

Villablanca, JG, London, WB, Naranjo, A, McGrady, P, Ames, MM, Reid, JM, McGovern, RM, Buhrow, SA, Jackson, H, Stranzinger, E, Kitchen, BJ, Sondel, PM, Parisi, MT, Shulkin, B, Yanik, GA, Cohn, SL & Patrick Reynolds, C 2011, 'Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: A report from the children's oncology group', Clinical Cancer Research, vol. 17, no. 21, pp. 6858-6866. https://doi.org/10.1158/1078-0432.CCR-11-0995
Villablanca, Judith G. ; London, Wendy B. ; Naranjo, Arlene ; McGrady, Patrick ; Ames, Matthew M. ; Reid, Joel M ; McGovern, Renee M. ; Buhrow, Sarah A. ; Jackson, Hollie ; Stranzinger, Enno ; Kitchen, Brenda J. ; Sondel, Paul M. ; Parisi, Marguerite T. ; Shulkin, Barry ; Yanik, Gregory A. ; Cohn, Susan L. ; Patrick Reynolds, C. / Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma : A report from the children's oncology group. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 21. pp. 6858-6866.
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abstract = "Purpose: To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma. Experimental Design: Patients received 7 days of fenretinide: 2,475 mg/m 2/d divided TID (<18 years) or 1,800 mg/m 2/d divided BID (≥18 years) every 21 days for a maximum of 30 courses. Patients with stable or responding disease after course 30 could request additional compassionate courses. Best response by course 8 was evaluated in stratum 1 (measurable disease on CT/MRI ± bone marrow and/or MIBG avid sites) and stratum 2 (bone marrow and/or MIBG avid sites only). Results: Sixty-two eligible patients, median age 5 years (range 0.6-19.9), were treated in stratum 1 (n = 38) and stratum 2 (n = 24). One partial response (PR) was seen in stratum 2 (n = 24 evaluable). No responses were seen in stratum 1 (n=35 evaluable). Prolonged stable disease (SD) was seen in 7 patients in stratum 1 and 6 patients in stratum 2 for 4 to 45+ (median 15) courses. Median time to progression was 40 days (range 17-506) for stratum 1 and 48 days (range 17-892) for stratum 2. Mean 4-HPR steady-state trough plasma concentrations were 7.25 μmol/L (coefficient of variation 40-56{\%}) at day 7 course 1. Toxicities were mild and reversible. Conclusions: Although neither stratum met protocol criteria for efficacy, 1 PR + 13 prolonged SD occurred in 14/59 (24{\%}) of evaluable patients. Low bioavailability may have limited fenretinide activity. Novel fenretinide formulations with improved bioavailability are currently in pediatric phase I studies.",
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T1 - Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma

T2 - A report from the children's oncology group

AU - Villablanca, Judith G.

AU - London, Wendy B.

AU - Naranjo, Arlene

AU - McGrady, Patrick

AU - Ames, Matthew M.

AU - Reid, Joel M

AU - McGovern, Renee M.

AU - Buhrow, Sarah A.

AU - Jackson, Hollie

AU - Stranzinger, Enno

AU - Kitchen, Brenda J.

AU - Sondel, Paul M.

AU - Parisi, Marguerite T.

AU - Shulkin, Barry

AU - Yanik, Gregory A.

AU - Cohn, Susan L.

AU - Patrick Reynolds, C.

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N2 - Purpose: To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma. Experimental Design: Patients received 7 days of fenretinide: 2,475 mg/m 2/d divided TID (<18 years) or 1,800 mg/m 2/d divided BID (≥18 years) every 21 days for a maximum of 30 courses. Patients with stable or responding disease after course 30 could request additional compassionate courses. Best response by course 8 was evaluated in stratum 1 (measurable disease on CT/MRI ± bone marrow and/or MIBG avid sites) and stratum 2 (bone marrow and/or MIBG avid sites only). Results: Sixty-two eligible patients, median age 5 years (range 0.6-19.9), were treated in stratum 1 (n = 38) and stratum 2 (n = 24). One partial response (PR) was seen in stratum 2 (n = 24 evaluable). No responses were seen in stratum 1 (n=35 evaluable). Prolonged stable disease (SD) was seen in 7 patients in stratum 1 and 6 patients in stratum 2 for 4 to 45+ (median 15) courses. Median time to progression was 40 days (range 17-506) for stratum 1 and 48 days (range 17-892) for stratum 2. Mean 4-HPR steady-state trough plasma concentrations were 7.25 μmol/L (coefficient of variation 40-56%) at day 7 course 1. Toxicities were mild and reversible. Conclusions: Although neither stratum met protocol criteria for efficacy, 1 PR + 13 prolonged SD occurred in 14/59 (24%) of evaluable patients. Low bioavailability may have limited fenretinide activity. Novel fenretinide formulations with improved bioavailability are currently in pediatric phase I studies.

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