A phase I study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 21 days every 28 days in pediatric patients with solid tumors

Elizabeth Fox, John M. Maris, Brigitte C. Widemann, Wendy Goodspeed, Anne Goodwin, Marie Kromplewski, Molly E. Fouts, Diane Medina, Susan L. Cohn, Andrew Krivoshik, Anne E. Hagey, Peter C. Adamson, Frank M. Balis

Research output: Contribution to journalArticle

Abstract

Purpose: To determine the toxicity profile, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) of ABT-751 administered orally once daily for 21days, repeated every 28 days in a pediatric population. Experimental Design: Patients who were V18 years with relapsed or refractory solid tumors and who were able to swallow capsules were eligible. The starting dose was 75 mg/m 2/d (n = 3) and was escalated to 100 (n = 6),130 (n = 5), and 165 (n = 3) mg/m2/d in cohorts of three to six patients. The MTD was determined from DLTs occurring during the first treatment cycle. Results: Nineteen children (median age, 13 years; range, 5-18 years) were enrolled, and 17 were evaluable for toxicity. Diagnoses included neuroblastoma (n = 9), sarcomas (n = 9), and other solid tumors (n = 1). DLTs included fatigue, sensory neuropathy, transient hypertension, neutropenia, thrombocytopenia, nausea, vomiting, dehydration, abdominal pain, and constipation. The MTD of ABT-751 administered daily for 21days every 28 days was 100 mg/m2/d. Non-DLTat the MTD included bone marrow suppression, gastrointestinal toxicities (anorexia, abdominal pain, nausea, vomiting, and constipation), and sensory and motor neuropathies. The median number of cycles administered was one (range, one to five). Tolerance of repeated treatment cycles was poor. Conclusion: Fatigue, hematologic, and gastrointestinal toxicities limited the tolerability of ABT-751 administered to children on the once daily for 21 days every 28 days schedule. The MTD in children with solid tumors (100 mg/m2/d daily for 21 days) was similar to the recommended dose in adults with solid tumors (200 mg fixed dose) receiving the same dosing schedule.

Original languageEnglish (US)
Pages (from-to)1111-1115
Number of pages5
JournalClinical Cancer Research
Volume14
Issue number4
DOIs
StatePublished - Feb 15 2008
Externally publishedYes

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Tubulin Modulators
Maximum Tolerated Dose
Pediatrics
Constipation
Neoplasms
Nausea
Abdominal Pain
Vomiting
Fatigue
Appointments and Schedules
Anorexia
Deglutition
Neutropenia
Neuroblastoma
Dehydration
Sarcoma
Thrombocytopenia
Capsules
Research Design
Bone Marrow

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A phase I study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 21 days every 28 days in pediatric patients with solid tumors. / Fox, Elizabeth; Maris, John M.; Widemann, Brigitte C.; Goodspeed, Wendy; Goodwin, Anne; Kromplewski, Marie; Fouts, Molly E.; Medina, Diane; Cohn, Susan L.; Krivoshik, Andrew; Hagey, Anne E.; Adamson, Peter C.; Balis, Frank M.

In: Clinical Cancer Research, Vol. 14, No. 4, 15.02.2008, p. 1111-1115.

Research output: Contribution to journalArticle

Fox, E, Maris, JM, Widemann, BC, Goodspeed, W, Goodwin, A, Kromplewski, M, Fouts, ME, Medina, D, Cohn, SL, Krivoshik, A, Hagey, AE, Adamson, PC & Balis, FM 2008, 'A phase I study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 21 days every 28 days in pediatric patients with solid tumors', Clinical Cancer Research, vol. 14, no. 4, pp. 1111-1115. https://doi.org/10.1158/1078-0432.CCR-07-4097
Fox, Elizabeth ; Maris, John M. ; Widemann, Brigitte C. ; Goodspeed, Wendy ; Goodwin, Anne ; Kromplewski, Marie ; Fouts, Molly E. ; Medina, Diane ; Cohn, Susan L. ; Krivoshik, Andrew ; Hagey, Anne E. ; Adamson, Peter C. ; Balis, Frank M. / A phase I study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 21 days every 28 days in pediatric patients with solid tumors. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 4. pp. 1111-1115.
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abstract = "Purpose: To determine the toxicity profile, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) of ABT-751 administered orally once daily for 21days, repeated every 28 days in a pediatric population. Experimental Design: Patients who were V18 years with relapsed or refractory solid tumors and who were able to swallow capsules were eligible. The starting dose was 75 mg/m 2/d (n = 3) and was escalated to 100 (n = 6),130 (n = 5), and 165 (n = 3) mg/m2/d in cohorts of three to six patients. The MTD was determined from DLTs occurring during the first treatment cycle. Results: Nineteen children (median age, 13 years; range, 5-18 years) were enrolled, and 17 were evaluable for toxicity. Diagnoses included neuroblastoma (n = 9), sarcomas (n = 9), and other solid tumors (n = 1). DLTs included fatigue, sensory neuropathy, transient hypertension, neutropenia, thrombocytopenia, nausea, vomiting, dehydration, abdominal pain, and constipation. The MTD of ABT-751 administered daily for 21days every 28 days was 100 mg/m2/d. Non-DLTat the MTD included bone marrow suppression, gastrointestinal toxicities (anorexia, abdominal pain, nausea, vomiting, and constipation), and sensory and motor neuropathies. The median number of cycles administered was one (range, one to five). Tolerance of repeated treatment cycles was poor. Conclusion: Fatigue, hematologic, and gastrointestinal toxicities limited the tolerability of ABT-751 administered to children on the once daily for 21 days every 28 days schedule. The MTD in children with solid tumors (100 mg/m2/d daily for 21 days) was similar to the recommended dose in adults with solid tumors (200 mg fixed dose) receiving the same dosing schedule.",
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T1 - A phase I study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 21 days every 28 days in pediatric patients with solid tumors

AU - Fox, Elizabeth

AU - Maris, John M.

AU - Widemann, Brigitte C.

AU - Goodspeed, Wendy

AU - Goodwin, Anne

AU - Kromplewski, Marie

AU - Fouts, Molly E.

AU - Medina, Diane

AU - Cohn, Susan L.

AU - Krivoshik, Andrew

AU - Hagey, Anne E.

AU - Adamson, Peter C.

AU - Balis, Frank M.

PY - 2008/2/15

Y1 - 2008/2/15

N2 - Purpose: To determine the toxicity profile, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) of ABT-751 administered orally once daily for 21days, repeated every 28 days in a pediatric population. Experimental Design: Patients who were V18 years with relapsed or refractory solid tumors and who were able to swallow capsules were eligible. The starting dose was 75 mg/m 2/d (n = 3) and was escalated to 100 (n = 6),130 (n = 5), and 165 (n = 3) mg/m2/d in cohorts of three to six patients. The MTD was determined from DLTs occurring during the first treatment cycle. Results: Nineteen children (median age, 13 years; range, 5-18 years) were enrolled, and 17 were evaluable for toxicity. Diagnoses included neuroblastoma (n = 9), sarcomas (n = 9), and other solid tumors (n = 1). DLTs included fatigue, sensory neuropathy, transient hypertension, neutropenia, thrombocytopenia, nausea, vomiting, dehydration, abdominal pain, and constipation. The MTD of ABT-751 administered daily for 21days every 28 days was 100 mg/m2/d. Non-DLTat the MTD included bone marrow suppression, gastrointestinal toxicities (anorexia, abdominal pain, nausea, vomiting, and constipation), and sensory and motor neuropathies. The median number of cycles administered was one (range, one to five). Tolerance of repeated treatment cycles was poor. Conclusion: Fatigue, hematologic, and gastrointestinal toxicities limited the tolerability of ABT-751 administered to children on the once daily for 21 days every 28 days schedule. The MTD in children with solid tumors (100 mg/m2/d daily for 21 days) was similar to the recommended dose in adults with solid tumors (200 mg fixed dose) receiving the same dosing schedule.

AB - Purpose: To determine the toxicity profile, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) of ABT-751 administered orally once daily for 21days, repeated every 28 days in a pediatric population. Experimental Design: Patients who were V18 years with relapsed or refractory solid tumors and who were able to swallow capsules were eligible. The starting dose was 75 mg/m 2/d (n = 3) and was escalated to 100 (n = 6),130 (n = 5), and 165 (n = 3) mg/m2/d in cohorts of three to six patients. The MTD was determined from DLTs occurring during the first treatment cycle. Results: Nineteen children (median age, 13 years; range, 5-18 years) were enrolled, and 17 were evaluable for toxicity. Diagnoses included neuroblastoma (n = 9), sarcomas (n = 9), and other solid tumors (n = 1). DLTs included fatigue, sensory neuropathy, transient hypertension, neutropenia, thrombocytopenia, nausea, vomiting, dehydration, abdominal pain, and constipation. The MTD of ABT-751 administered daily for 21days every 28 days was 100 mg/m2/d. Non-DLTat the MTD included bone marrow suppression, gastrointestinal toxicities (anorexia, abdominal pain, nausea, vomiting, and constipation), and sensory and motor neuropathies. The median number of cycles administered was one (range, one to five). Tolerance of repeated treatment cycles was poor. Conclusion: Fatigue, hematologic, and gastrointestinal toxicities limited the tolerability of ABT-751 administered to children on the once daily for 21 days every 28 days schedule. The MTD in children with solid tumors (100 mg/m2/d daily for 21 days) was similar to the recommended dose in adults with solid tumors (200 mg fixed dose) receiving the same dosing schedule.

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