A Phase I Study of Vincristine, Irinotecan, Temozolomide and Bevacizumab (Vitb) in Pediatric Patients with Relapsed Solid Tumors

Rajkumar Venkatramani, Marcio Malogolowkin, Tom B. Davidson, William May, Richard Sposto, Leo Mascarenhas

Research output: Contribution to journalArticle

19 Citations (Scopus)

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/m2, and DL2: 50 mg/m2), combined with vincristine 1.5 mg/m2 on days 1 and 8, temozolomide 100 mg/m2 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/m2/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.

Original languageEnglish (US)
Article numbere68416
JournalPLoS One
Volume8
Issue number7
DOIs
StatePublished - Jul 22 2013
Externally publishedYes

Fingerprint

irinotecan
temozolomide
vincristine
Pediatrics
Vincristine
Toxicity
Tumors
neoplasms
Maximum Tolerated Dose
dosage
Neoplasms
Refractory materials
toxicity
Diarrhea
Gilbert Disease
diarrhea
Intestinal Perforation
Leukoencephalopathies
Medulloblastoma
Growth Plate

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

A Phase I Study of Vincristine, Irinotecan, Temozolomide and Bevacizumab (Vitb) in Pediatric Patients with Relapsed Solid Tumors. / Venkatramani, Rajkumar; Malogolowkin, Marcio; Davidson, Tom B.; May, William; Sposto, Richard; Mascarenhas, Leo.

In: PLoS One, Vol. 8, No. 7, e68416, 22.07.2013.

Research output: Contribution to journalArticle

Venkatramani, Rajkumar ; Malogolowkin, Marcio ; Davidson, Tom B. ; May, William ; Sposto, Richard ; Mascarenhas, Leo. / A Phase I Study of Vincristine, Irinotecan, Temozolomide and Bevacizumab (Vitb) in Pediatric Patients with Relapsed Solid Tumors. In: PLoS One. 2013 ; Vol. 8, No. 7.
@article{70a7ac1ecd7446559448b15367d8bb41,
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/m2, and DL2: 50 mg/m2), combined with vincristine 1.5 mg/m2 on days 1 and 8, temozolomide 100 mg/m2 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/m2/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 = "Rajkumar Venkatramani and Marcio Malogolowkin and Davidson, {Tom B.} and William May and Richard Sposto and Leo Mascarenhas",
year = "2013",
month = "7",
day = "22",
doi = "10.1371/journal.pone.0068416",
language = "English (US)",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - A Phase I Study of Vincristine, Irinotecan, Temozolomide and Bevacizumab (Vitb) in Pediatric Patients with Relapsed Solid Tumors

AU - Venkatramani, Rajkumar

AU - Malogolowkin, Marcio

AU - Davidson, Tom B.

AU - May, William

AU - Sposto, Richard

AU - Mascarenhas, Leo

PY - 2013/7/22

Y1 - 2013/7/22

N2 - 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/m2, and DL2: 50 mg/m2), combined with vincristine 1.5 mg/m2 on days 1 and 8, temozolomide 100 mg/m2 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/m2/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.

AB - 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/m2, and DL2: 50 mg/m2), combined with vincristine 1.5 mg/m2 on days 1 and 8, temozolomide 100 mg/m2 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/m2/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.

UR - http://www.scopus.com/inward/record.url?scp=84880684324&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880684324&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0068416

DO - 10.1371/journal.pone.0068416

M3 - Article

C2 - 23425509

AN - SCOPUS:84880684324

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e68416

ER -