Faculty Collaboration Database

A phase I study of vincristine, irinotecan, temozolomide and bevacizumab (vitb) in pediatric patients with relapsed solid tumors. PLoS One 2013;8(7):e68416

Date

07/31/2013

Pubmed ID

23894304

Pubmed Central ID

PMC3718768

DOI

10.1371/journal.pone.0068416

Scopus ID

2-s2.0-84880684324 (requires institutional sign-in at Scopus site)   38 Citations

Abstract

BACKGROUND: To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of irinotecan administered in combination with vincristine, temozolomide and bevacizumab in children with refractory solid tumors.

METHODS: The study design included two dose levels (DL) of irinotecan given intravenously once daily for 5 consecutive days (DL1: 30 mg/m(2), and DL2: 50 mg/m(2)), combined with vincristine 1.5 mg/m(2) on days 1 and 8, temozolomide 100 mg/m(2) on days 1-5, and bevacizumab 15mg/kg on day 1, administered every 21 days for a maximum of 12 cycles.

RESULTS: Thirteen patients were enrolled and 12 were evaluable for toxicity Dose limiting toxicity observed included grade 3 hyperbilirubinemia in 1 of 6 patients on DL1, and grade 3 colitis in 1 of 6 patients on DL2. DL 2 was the determined MTD. A total of 87 cycles were administered. Myelosuppression was mild. Grade 1-2 diarrhea occurred in the majority of cycles with grade 3 diarrhea occurring in only one cycle. Grade 2 hypertension developed in two patients. Severe hemorrhage, intestinal perforation, posterior leukoencephalopathy or growth plate abnormalities were not observed. Objective responses were noted in three Wilms tumor patients and one each of medulloblastoma and hepatocellular carcinoma. Five patients completed all 12 cycles of protocol therapy.

CONCLUSIONS: Irinotecan 50 mg/m(2)/day for 5 days was the MTD when combined with vincristine, temozolomide and bevacizumab administered on a 21 day schedule. Encouraging anti-tumor activity was noted.

TRIAL REGISTRATION: ClinicalTrials.gov; NCT00993044; http://clinicaltrials.gov/show/NCT00993044.

Author List

Venkatramani R, Malogolowkin M, Davidson TB, May W, Sposto R, Mascarenhas L

MESH terms used to index this publication - Major topics in bold

Adolescent
Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Bevacizumab
Camptothecin
Child
Child, Preschool
Dacarbazine
Dose-Response Relationship, Drug
Female
Humans
Male
Maximum Tolerated Dose
Neoplasms
Recurrence
Vincristine
Young Adult