Phase I study of vincristine, irinotecan, and ¹³¹I-metaiodobenzylguanidine for patients with relapsed or refractory neuroblastoma: a new approaches to neuroblastoma therapy trial.

Abstract

PURPOSE:

(131)I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical with activity in patients with relapsed or refractory neuroblastoma. Irinotecan is a known radiosensitizer with activity in neuroblastoma. This phase I study aimed to determine the recommended phase 2 dose of MIBG together with fixed doses of vincristine and irinotecan.

EXPERIMENTAL DESIGN:

Patients 1 to 30 years old with relapsed or refractory neuroblastoma and MIBG-avid tumors were eligible. All patients had autologous hematopoietic stem cells (PBSC) available and met standard phase I organ function requirements. Irinotecan (20 mg/m(2)/dose IV) was given on days 0 to 4 and 7 to 11, with vincristine (1.5 mg/m(2) IV) on days 0 and 7. MIBG was given on day 1 following a 3 + 3 phase I dose escalation design starting at 8 mCi/kg MIBG. PBSCs were administered at dose level 8 mCi/kg for prolonged myelosuppression and for all patients at 12 mCi/kg or more.

RESULTS:

Twenty-four patients evaluable for dose escalation (median age, 6.7 years; range, 1.9-26.8 years) received 1 (n = 17), 2 (n = 5), or 3 (n = 2) cycles of therapy. Myelosuppression and diarrhea were the most common toxicities. Two of 6 patients at the 18 mCi/kg dose level had dose-limiting toxicity (DLT), including one with protocol-defined DLT with prolonged mild aspartate aminotransferase elevation. Eighteen mCi/kg was the recommended phase 2 dose. Six additional patients were treated at 18 mCi/kg, with one additional DLT. Responses (2 complete and 4 partial responses) occurred in 6 of 24 (25%) evaluable patients.

CONCLUSIONS:

MIBG is tolerable and active at 18 mCi/kg with standard doses of vincristine and irinotecan.

• Authors: Steven G DuBois, Louis Chesler, Susan Groshen, Randall Hawkins, Fariba Goodarzian, Hiroyuki Shimada, Greg Yanik, Michael Tagen, Clinton Stewart, Yael P Mosse, John M Maris, Denice Tsao-Wei, Araz Marachelian, Judith G Villablanca, Katherine K Matthay
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 18 Issue 9 Pg. 2679-86 (May 01 2012) ISSN: 1557-3265 [Electronic] United States
• PMID: 22421195 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR.

Chemical References

• Iodine Radioisotopes
• 3-Iodobenzylguanidine
• Vincristine
• Irinotecan
• Camptothecin

Topics

• 3-Iodobenzylguanidine (administration & dosage)
• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (pharmacokinetics, therapeutic use)
• Camptothecin (administration & dosage, analogs & derivatives)
• Child
• Child, Preschool
• Female
• Follow-Up Studies
• Humans
• Infant
• Iodine Radioisotopes (pharmacokinetics, therapeutic use)
• Irinotecan
• Male
• Maximum Tolerated Dose
• Neuroblastoma (drug therapy)
• Prognosis
• Tissue Distribution
• Vincristine (administration & dosage)
• Young Adult