Heike Daldrup-Link

Publication Details

  • Phase I Trial of Oral Irinotecan and Temozolomide for Children With Relapsed High-Risk Neuroblastoma: A New Approach to Neuroblastoma Therapy Consortium Study JOURNAL OF CLINICAL ONCOLOGY Wagner, L. M., Villablanca, J. G., Stewart, C. F., Crews, K. R., Groshen, S., Reynolds, C. P., Park, J. R., Maris, J. M., Hawkins, R. A., Daldrup-Link, H. E., Jackson, H. A., Matthay, K. K. 2009; 27 (8): 1290-1296

    Abstract:

    Irinotecan and temozolomide have single-agent activity and schedule-dependent synergy against neuroblastoma. Because protracted administration of intravenous irinotecan is costly and inconvenient, we sought to determine the maximum-tolerated dose (MTD) of oral irinotecan combined with temozolomide in children with recurrent/resistant high-risk neuroblastoma.Patients received oral temozolomide on days 1 through 5 combined with oral irinotecan on days 1 through 5 and 8 through 12 in 3-week courses. Daily oral cefixime was used to reduce irinotecan-associated diarrhea.Fourteen assessable patients received 75 courses. Because neutropenia and thrombocytopenia were initially dose-limiting, temozolomide was reduced from 100 to 75 mg/m(2)/d for subsequent patients. Irinotecan was then escalated from 30 to 60 mg/m2/d. First-course grade 3 diarrhea was dose-limiting in one of six patients treated at the irinotecan MTD of 60 mg/m2/d. Other toxicities were mild and reversible. The median SN-38 lactone area under the plasma concentration versus time curve at this dose was 72 ng . hr/mL. One patient with bulky soft tissue disease had a complete response through six courses. Six additional patients received a median of seven courses (range, three to 22 courses) before progression.This all-oral regimen was feasible and well tolerated in heavily pretreated children with resistant neuroblastoma, and seven (50%) of 14 assessable patients had response or disease stabilization for three or more courses in this phase I trial. SN-38 lactone exposures were similar to those reported with protracted intravenous irinotecan. The dosages recommended for further study in this patient population are temozolomide 75 mg/m2/d plus irinotecan 60 mg/m2/d when given with cefixime.

    View details for DOI 10.1200/JCO.2008.18.5918

    View details for Web of Science ID 000266193700028

    View details for PubMedID 19171709

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