TY - JOUR
T1 - Phase I and pharmacokinetic study of CI-980 in recurrent pediatric solid tumor cases
T2 - A pediatric oncology group study
AU - Bernstein, Mark L.
AU - Baruchel, Sylvain
AU - Devine, Susan
AU - Markoglou, Nektaria
AU - Wainer, Irving W.
AU - Williams, Marion
AU - Blaney, Susan
AU - Moghrabi, Albert
AU - Winick, Naomi
AU - Vietti, Teresa
PY - 1999
Y1 - 1999
N2 - To establish the maximum tolerated dosage (MTD), the dose-limiting toxicities (DLTs), and pharmacokinetic parameters of CI-980, a novel tubulin binder, in children with solid tumors refractory to standard therapy. Patients 21 years of age or younger with adequate nutritional, hematopoietic, renal, and hepatic function were eligible. The patient must not have been pregnant. Patients with brain tumors were not eligible for any dosage level until it was demonstrated the level did not produce DLT in patients with extracranial solid tumors. The starting dosage level was 3.5 mg/m2/day, for 3 days, administered as a continuous intravenous infusion (80% of the adult MTD). If a dosage level was associated with dose-limiting myelotoxicity, growth factors were to be added. Thirty-three patients received CI-980. Twenty-four had solid tumor; 9 had brain tumor. The MTD achieved without granulocyte colony stimulating factor (G-CSF) was 3.5 mg/m2/day (DLT: neutropenia) and with G-CSF, it was as follows: patients with brain tumor, 4.2 mg/m2/day (DLT: myelosupression); and patients with solid tumor, 5 mg/m2/day (DLT: cortical toxicity). Several responses were seen, most notably prolonged stable disease in two of five patients with medulloblastoma. Pharmacokinetic data showed a mean steady state level of 1.74 ng/mL for two patients treated with the 5 mg/m2/day regimen, with rapid decay after the termination of the infusion. CI-980 showed preliminary evidence of activity in recurrent pediatric malignancies, with tolerable, reversible toxicities.
AB - To establish the maximum tolerated dosage (MTD), the dose-limiting toxicities (DLTs), and pharmacokinetic parameters of CI-980, a novel tubulin binder, in children with solid tumors refractory to standard therapy. Patients 21 years of age or younger with adequate nutritional, hematopoietic, renal, and hepatic function were eligible. The patient must not have been pregnant. Patients with brain tumors were not eligible for any dosage level until it was demonstrated the level did not produce DLT in patients with extracranial solid tumors. The starting dosage level was 3.5 mg/m2/day, for 3 days, administered as a continuous intravenous infusion (80% of the adult MTD). If a dosage level was associated with dose-limiting myelotoxicity, growth factors were to be added. Thirty-three patients received CI-980. Twenty-four had solid tumor; 9 had brain tumor. The MTD achieved without granulocyte colony stimulating factor (G-CSF) was 3.5 mg/m2/day (DLT: neutropenia) and with G-CSF, it was as follows: patients with brain tumor, 4.2 mg/m2/day (DLT: myelosupression); and patients with solid tumor, 5 mg/m2/day (DLT: cortical toxicity). Several responses were seen, most notably prolonged stable disease in two of five patients with medulloblastoma. Pharmacokinetic data showed a mean steady state level of 1.74 ng/mL for two patients treated with the 5 mg/m2/day regimen, with rapid decay after the termination of the infusion. CI-980 showed preliminary evidence of activity in recurrent pediatric malignancies, with tolerable, reversible toxicities.
KW - CI-980
KW - Granulocyte colony stimulating factor (G-CSF)
KW - Phase I trial
UR - http://www.scopus.com/inward/record.url?scp=0033503146&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033503146&partnerID=8YFLogxK
U2 - 10.1097/00043426-199911000-00009
DO - 10.1097/00043426-199911000-00009
M3 - Article
C2 - 10598660
AN - SCOPUS:0033503146
SN - 1077-4114
VL - 21
SP - 494
EP - 500
JO - Journal of Pediatric Hematology/Oncology
JF - Journal of Pediatric Hematology/Oncology
IS - 6
ER -