Phase II Study of Irinotecan and Temozolomide in Children With Relapsed or Refractory Neuroblastoma: A Children's Oncology Group Study

• Published in: Journal of clinical oncology Vol. 29; no. 2; pp. 208 - 213
• Main Authors: Bagatell, Rochelle, London, Wendy B., Wagner, Lars M., Voss, Stephan D., Stewart, Clinton F., Maris, John M., Kretschmar, Cynthia, Cohn, Susan L.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.01.2011
• Subjects: Adolescent; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Child; Child, Preschool; Dacarbazine - administration & dosage; Dacarbazine - adverse effects; Dacarbazine - analogs & derivatives; Disease-Free Survival; Female; Humans; Infant; Male; Medical sciences; Neuroblastoma - drug therapy; Neurology; Original Reports; Tumors; Tumors of the nervous system. Phacomatoses; Camptothecin derivatives; Human; Antineoplastic agent; Nervous system diseases; Relapse; Treatment resistance; Enzyme; DNA topoisomerase; Enzyme inhibitor; Neuroblastoma; Malignant tumor; Irinotecan; Alkylating agent; Isomerases; Cancerology; Treatment; Phase II trial; Temozolomide; Autonomic neuropathy; Topoisomerase I inhibitor; Child; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2010.31.7107

This phase II study was conducted to determine the response rate associated with use of irinotecan and temozolomide for children with relapsed/refractory neuroblastoma. Patients with relapsed/refractory neuroblastoma measurable by cross-sectional imaging (stratum 1) or assessable by bone marrow aspirate/biopsy or metaiodobenzylguanidine (MIBG) scan (stratum 2) received irinotecan (10 mg/m(2)/dose 5 days a week for 2 weeks) and temozolomide (100 mg/m(2)/dose for 5 days) every 3 weeks. Response was assessed after three and six courses using International Neuroblastoma Response Criteria. Of the first 25 evaluable patients on a given stratum, five or more patients with complete or partial responses were required to conclude that further study would be merited. Fifty-five eligible patients were enrolled. The objective response rate was 15%. Fourteen patients (50%) on stratum 1 and 15 patients (56%) on stratum 2 had stable disease. Objective responses were observed in three of the first 25 evaluable patients on stratum 1 and five of the first 25 evaluable patients on stratum 2. Less than 6% of patients experienced ≥ grade 3 diarrhea. Although neutropenia was observed, less than 10% of patients developed evidence of infection while neutropenic. The combination of irinotecan and temozolomide was well tolerated. The objective response rate of 19% in stratum 2 suggests that this combination may be effective for patients with neuroblastoma detectable by MIBG or marrow analysis. Although fewer objective responses were observed in patients with disease measurable by computed tomography/magnetic resonance imaging, patients in both strata seem to have derived clinical benefit from this therapy.