In:
Pediatric Blood & Cancer, Wiley, Vol. 54, No. 4 ( 2010-04), p. 538-545
Kurzfassung:
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 × 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 ≥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. Pediatr Blood Cancer 2010;54:538–545. © 2009 Wiley‐Liss, Inc.
Materialart:
Online-Ressource
ISSN:
1545-5009
,
1545-5017
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2010
ZDB Id:
2130978-4
