Phase I trial of two schedules of vincristine, oral irinotecan, and temozolomide (VOIT) for children with relapsed or refractory solid tumors: a Children's Oncology Group phase I consortium study

Pediatr Blood Cancer. 2010 Apr;54(4):538-45. doi: 10.1002/pbc.22407.


Background: In preclinical models, temozolomide, and vincristine are additive or synergistic with irinotecan. We examined this three-drug combination in children with relapsed solid tumors. Patients received orally administered irinotecan together with temozolomide and vincristine on two different schedules, using cefixime to reduce irinotecan-associated diarrhea.

Methods: Oral irinotecan was given daily on days 1-5 and 8-12 (Schedule A), or on days 1-5 (Schedule B). Temozolomide was given on days 1-5, with vincristine 1.5 mg/m(2) administered on days 1 and 8 (Schedule A) or day 1 (Schedule B) in 21-day courses.

Results: On Schedule A, the maximum tolerated dose of oral irinotecan was 35 mg/m(2)/day combined with temozolomide 100 mg/m(2)/day and vincristine on days 1 and 8. Dose-limiting toxicities in 4 of 12 patients included hepatotoxicity, abdominal pain, anorexia, hypokalemia, and thrombocytopenia at 50 mg/m(2)/day. Using Schedule B, 0 of 6 patients experienced dose-limiting toxicity (DLT) at the highest doses studied of oral irinotecan 90 mg/m(2)/day, temozolomide 150 mg/m(2)/day x 5, and vincristine on day 1. First-course and cumulative toxicity was greater with Schedule A. UGT1A1*28 genotype did not correlate with DLT. At the irinotecan dose of 90 mg/m(2)/day, the mean SN-38 AUC(inf) was 63 ng/ml hr. Activity was seen in sarcoma patients, and overall eight patients received >or=6 courses.

Conclusions: The 5-day schedule of VOIT was well tolerated and provided SN-38 exposures similar to those achieved with intravenous IRN. Activity on this and prior studies suggests a potential role for VOIT in a spectrum of childhood solid tumors.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Area Under Curve
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacokinetics
  • Child
  • Child, Preschool
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / pharmacokinetics
  • Female
  • Humans
  • Infant
  • Irinotecan
  • Male
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasms / drug therapy*
  • Temozolomide
  • Vincristine / administration & dosage
  • Vincristine / adverse effects
  • Vincristine / pharmacokinetics
  • Young Adult


  • Vincristine
  • Irinotecan
  • Dacarbazine
  • Camptothecin
  • Temozolomide