A phase I study of vincristine, irinotecan, temozolomide and bevacizumab (vitb) in pediatric patients with relapsed solid tumors

PLoS One. 2013 Jul 22;8(7):e68416. doi: 10.1371/journal.pone.0068416. Print 2013.

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Bevacizumab
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Camptothecin / therapeutic use
  • Child
  • Child, Preschool
  • Dacarbazine / adverse effects
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / pharmacology
  • Dacarbazine / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Irinotecan
  • Male
  • Maximum Tolerated Dose
  • Neoplasms / drug therapy*
  • Recurrence
  • Temozolomide
  • Vincristine / adverse effects
  • Vincristine / pharmacology
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Bevacizumab
  • Vincristine
  • Irinotecan
  • Dacarbazine
  • Camptothecin
  • Temozolomide

Associated data

  • ClinicalTrials.gov/NCT00993044