A phase 2 trial of all-trans-retinoic acid in combination with interferon-alpha2a in children with recurrent neuroblastoma or Wilms tumor: A Pediatric Oncology Branch, NCI and Children's Oncology Group Study.
BACKGROUND
The combination of the antiproliferative and differentiation-inducing effects of retinoids together with the antiproliferative, immunostimulatory, and differentiation-potentiating effects of interferon-alpha (IFN-alpha) were the basis for the development of this combination in pediatric patients with refractory neuroblastoma or Wilms tumor.


METHODS
A phase 2 trial of all-trans-retinoic acid (ATRA), administered orally at a dose of 90 mg/m(2)/day in three divided doses for 3 consecutive days per week, and IFN-alpha2a, administered subcutaneously daily at a dose of 3 x 10(6) U/m(2)/day for 5 consecutive days per week, in 4 week cycles was performed. A two-stage design was used for each disease stratum.


RESULTS
Seventeen patients (16 evaluable) with neuroblastoma, median age 9 years, and 15 patients (14 evaluable) with Wilms tumor, median age 6 years, were enrolled. Overall, the combination was well tolerated, with headache being the most common toxicity observed. There were no complete or partial responses. The median number of cycles administered was 1 (range 1-9). Four patients with neuroblastoma had stable disease for 12 or more weeks.


CONCLUSIONS
The combination of ATRA and IFN-alpha2a was inactive in children with relapsed or refractory neuroblastoma and Wilms tumor. The lack of activity with this combination in children with refractory neuroblastoma is similar to the disappointing phase 2 results of single agent 13-cis-retinoic-acid (13cRA) and does not support further development of ATRA for children with relapsed neuroblastoma.
Adamson
Peter C
PC
The Children's Hospital of Philadelphia, Philadelphia, PA, USA. adamsonp@mail.med.upenn.edu
Matthay
Katherine K
KK
O'Brien
Michelle
M
Reaman
Gregory H
GH
Sato
Judith K
JK
Balis
Frank M
FM
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D006801:Humans; D007223:Infant; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000633:toxicity; D009447:Neuroblastoma / Q000150:complications / Q000188:drug therapy*; D011994:Recombinant Proteins; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage* / Q000633:toxicity; D009396:Wilms Tumor / Q000150:complications / Q000188:drug therapy*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014212:Tretinoin