title: A phase I study of vincristine, irinotecan, temozolomide and bevacizumab (vitb) in pediatric patients with relapsed solid tumors.
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.
  
  
  BACKGROUND
  ClinicalTrials.gov; NCT00993044; http://clinicaltrials.gov/show/NCT00993044.
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California, USA. rvenkatramani@chla.usc.edu
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Venkatramani
authors.forename: Marcio
authors.initials: M
authors.lastname: Malogolowkin
authors.forename: Tom B
authors.initials: TB
authors.lastname: Davidson
authors.forename: William
authors.initials: W
authors.lastname: May
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.forename: Leo
authors.initials: L
authors.lastname: Mascarenhas
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D000068258:Bevacizumab; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000188:drug therapy*; D012008:Recurrence; D000077204:Temozolomide; D014750:Vincristine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D014750:Vincristine; D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide
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