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Phase I Study of IGF-Methotrexate Conjugate in the Treatment of Advanced Tumors Expressing IGF-1R.
Venepalli, Neeta K; Emmadi, Rajyasree; Danciu, Oana C; Chowdhery, Rozina; Cabay, Robert J; Gaitonde, Sujata; Aardsma, Nathan; Kothari, Rajul; Liu, Li C; Fischer, James H; Zaidi, Ayesha; Russell, Meredith J; Dudek, Arkadiusz Z.
Afiliación
  • Venepalli NK; Department of Medicine, Division of Hematology/Oncology.
  • Emmadi R; Departments of Pathology.
  • Danciu OC; Department of Medicine, Division of Hematology/Oncology.
  • Chowdhery R; Department of Medicine, Division of Hematology/Oncology.
  • Cabay RJ; Departments of Pathology.
  • Gaitonde S; Departments of Pathology.
  • Aardsma N; Departments of Pathology.
  • Kothari R; Gynecology-Oncology.
  • Liu LC; Division of Epidemiology and Biostatistics School of Public Health.
  • Fischer JH; Department of Pharmacy Practice, College of Pharmacy.
  • Zaidi A; Oncology Clinical Trials Office, University of Illinois at Chicago, Chicago, IL.
  • Russell MJ; Oncology Clinical Trials Office, University of Illinois at Chicago, Chicago, IL.
  • Dudek AZ; Department of Medicine, Division of Hematology/Oncology.
Am J Clin Oncol ; 42(11): 862-869, 2019 11.
Article en En | MEDLINE | ID: mdl-31633515
OBJECTIVES: Insulin-like growth factor-methotrexate (IGF-MTX) is a conjugate of methotrexate and 765IGF, a variant of IGF-1 with high affinity for insulin-like growth factor type 1 receptor. The study aim was to determine the maximum tolerated dose of IGF-MTX in refractory solid organ and hematologic malignancies expressing insulin-like growth factor type 1 receptor. MATERIALS AND METHODS: This phase I trial used a modified toxicity probability interval design with 5 cohort dose levels, and expansion cohort at maximum tolerated dose. IGF-MTX was given intravenously over 90 minutes on days 1, 8, and 15 of a 28-day cycle. RESULTS: A total of 17 patients were enrolled. The highest tolerated dose tested was 0.80 µEq/kg with dose-limiting toxicity of grade 3 hypoglycemia. Drug-related grade 3 and 4 toxicities included abdominal pain (26%), hypoglycemia (10%), and hypotension (10%). Of the 15 evaluable for response, 3 patients (20%) had stable disease, including the patient with Hodgkin lymphoma with stable disease for 12 cycles of therapy. IGF-MTX concentrations declined rapidly, with half-lives of 5.2 to 14 minutes for the initial distribution phase and 6.5 to 7.5 hours for the terminal elimination phase. Higher IGF-R1 expression did not correlate with better outcome. CONCLUSIONS: IGF-MTX is well tolerated. IGF-MTX pharmacokinetics suggest rapid cellular uptake. The activity of IGF-MTX in Hodgkin lymphoma should be explored.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Metotrexato / Receptor IGF Tipo 1 / Neoplasias Hematológicas / Neoplasias Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: America do norte Idioma: En Revista: Am J Clin Oncol Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Metotrexato / Receptor IGF Tipo 1 / Neoplasias Hematológicas / Neoplasias Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: America do norte Idioma: En Revista: Am J Clin Oncol Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos