Phase II trial of ixabepilone administered daily for five days in children and young adults with refractory solid tumors: A report from the children's oncology group Journal Article
| Authors: | Jacobs, S.; Fox, E.; Krailo, M.; Hartley, G.; Navid, F.; Wexler, L.; Blaney, S. M.; Goodwin, A.; Goodspeed, W.; Balis, F. M.; Adamson, P. C.; Widemann, B. C. |
| Article Title: | Phase II trial of ixabepilone administered daily for five days in children and young adults with refractory solid tumors: A report from the children's oncology group |
| Abstract: | Purpose: Ixabepilone is a microtubule-stabilizing agent with activity in adult solid tumors and in pediatric tumor xenograft models that are resistant to paclitaxel. The maximum tolerated dose on the daily-for-5-days i.v. schedule was 6 mg/m2/dose in adults and 8 mg/m2/dose in children, and the primary dose-limiting toxicity (DLT) was neutropenia. This study aimed to determine the response rate to ixabepilone in six solid tumor strata in children and young adults. Experimental Design: We conducted a phase II trial of ixabepilone (8 mg/m2/dose for 5 days every 21 days) using a two-stage design in taxane-naïve children and young adults with treatment-refractory, measurable rhabdomyosarcoma, Ewing sarcoma family tumors, osteosarcoma, synovial sarcoma, or malignant peripheral nerve sheath tumor, neuroblastoma, and Wilms tumor. Results: Sixty-one eligible patients (36 male) were enrolled. Median (range) age was 13 years (range, 3-36). Fifty-nine patients were fully evaluable for toxicity and response. DLTs, most commonly myelosuppression, occurred in 11 patients (15% incidence in 3-18 years old and 33% in 19-36 years old; P = 0.2) during cycle 1. The median (range) number of cycles was 2 (range, 1-38). No partial or complete responses (response evaluation criteria in solid tumors) were observed. Seven patients received ≥3 cycles, and two had prolonged stable disease (Wilms' tumor, 38 cycles; synovial sarcoma, 8 cycles). Conclusions: Ixabepilone at 8 mg/m2/dose daily for 5 days was tolerable in children and adolescents, but did not show evidence of clinical activity in the childhood solid tumors studied. ©2010 AACR. |
| Keywords: | osteosarcoma; adolescent; adult; child; preschool child; school child; treatment outcome; child, preschool; young adult; major clinical study; clinical trial; drug tolerability; fatigue; neutropenia; drug dose reduction; drug withdrawal; hypertension; side effect; solid tumor; antineoplastic agents; recurrent cancer; anorexia; neoplasms; multiple cycle treatment; pain; phase 2 clinical trial; sensory neuropathy; anemia; bone marrow suppression; bleeding; thrombocytopenia; dehydration; myalgia; drug administration schedule; dose-response relationship, drug; drug resistance, neoplasm; groups by age; aminotransferase blood level; drug fever; drug hypersensitivity; ewing sarcoma; febrile neutropenia; hyperglycemia; hypomagnesemia; lymphocytopenia; chemotherapy induced emesis; hyponatremia; neuroblastoma; tumor burden; drug response; nausea and vomiting; maximum tolerated dose; childhood; rhabdomyosarcoma; synovial sarcoma; aphasia; malignant peripheral nerve sheath tumor; nerve sheath tumor; nephroblastoma; ixabepilone; epothilones; diphenhydramine; central nervous system disease; ranitidine |
| Journal Title: | Clinical Cancer Research |
| Volume: | 16 |
| Issue: | 2 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2010-01-15 |
| Start Page: | 750 |
| End Page: | 754 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-09-1906 |
| PUBMED: | 20068084 |
| PROVIDER: | scopus |
| PMCID: | PMC3086796 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: CCREF" - "Source: Scopus" |
