Randomized phase II study of carboplatin and irinotecan or irinotecan in 1–21 year old patients with refractory solid tumors

Abstract

8559 Background: Carboplatin and irinotecan have been shown to be active in pediatric tumors. Methods: The primary objective of this non-comparative, randomized study is to estimate the response rate of carboplatin AUC 4 mg/ml*min every 21 days in combination with irinotecan 12 mg/m2/day daily × 10 days every 21 days, with growth factor support (Arm A), and irinotecan 20 mg/m2/day daily × 10 days every 21 days(Arm B) in children with refractory solid tumors. The Arm A dose and schedule were determined by a prior phase I study (2003 AACR abst. #3567). One hundred and fifty-one patients were randomized and stratified by site of the primary tumor (non-CNS or CNS) and 148 were treated- 46 non-CNS and 28 CNS on Arm A, and 47 non-CNS and 27 CNS on Arm B. Non-CNS tumor types included osteosarcoma 19 (20%), rhabdomyosarcoma (RMS) 16 (17%), neuroblastoma 15 (16%), Wilm's tumor 12 (13%), sarcomas 9 (10%), retinoblastoma 5 (5%), Ewing's sarcoma 3 (3%), and others 15 (16%). CNS tumor types included gliomas (all grades) 24 (44%), medulloblastoma 10 (18%), ependymoma 9 (16%), and others 11 (20%). Results: Grade 3–4 non-hematologic toxicities in Arm A and B included infection/febrile neutropenia in 45% and 35% of patients, diarrhea in 41% and 42%, vomiting in 35% and 35%, abdominal pain/cramping in 23% and 18%, and nausea in 14% and 23%, respectively. Additional grade 3–4 non-hematologic toxicities in patients with CNS primary tumors on Arm A and B included seizures in 21% and 30% of patients, headache in 21% and 26%, ataxia in 21% and 7%, and motor neuropathy in 21% and 26%, respectively. Grade 3–4 hematologic toxicities in Arm A and B included thrombocytopenia in 20% and 3% of patients, neutropenia in 19% and 9%, and anemia in 24% and 14%, respectively. On Arm A, confirmed partial responses (PR) occurred in 2 patients (pineoblastoma and astrocytoma) and 38 patients had stable disease (SD). On Arm B, there was a confirmed complete response (CR) (neuroblastoma), and 3 PRs (RMS-2, peripheral neuroectodermal tumor). SD was noted in 35 patients. In both arms, several unconfirmed responses in evolution have been classified as SD. Conclusion: Final results will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb