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Phase II study of the c-MET inhibitor tivantinib (ARQ 197) in patients with relapsed or relapsed/refractory multiple myeloma.
Baljevic, Muhamed; Zaman, Shadia; Baladandayuthapani, Veerabhadran; Lin, Yan Heather; de Partovi, Claudia Morales; Berkova, Zuzana; Amini, Behrang; Thomas, Sheeba K; Shah, Jatin J; Weber, Donna M; Fu, Min; Cleeland, Charles S; Wang, Xin Shelley; Stellrecht, Christine M; Davis, Richard E; Gandhi, Varsha; Orlowski, Robert Z.
Afiliación
  • Baljevic M; Division of Hematology & Oncology, The University of Nebraska Medical Center, Omaha, NE, USA.
  • Zaman S; Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Baladandayuthapani V; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Lin YH; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • de Partovi CM; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Berkova Z; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Amini B; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Thomas SK; Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Shah JJ; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Weber DM; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Fu M; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Cleeland CS; Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wang XS; Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Stellrecht CM; Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Davis RE; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Gandhi V; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Orlowski RZ; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ann Hematol ; 96(6): 977-985, 2017 Jun.
Article en En | MEDLINE | ID: mdl-28337527
The hepatocyte growth factor/c-MET pathway has been implicated in the pathobiology of multiple myeloma, and c-MET inhibitors induce myeloma cell apoptosis, suggesting that they could be useful clinically. We conducted a phase II study with the c-MET inhibitor tivantinib in patients with relapsed, or relapsed and refractory myeloma whose disease had progressed after one to four prior therapies. Tivantinib, 360 mg orally per dose, was administered twice daily continuously over a 4-week treatment cycle without a cap on the number of allowed cycles, barring undue toxicities or disease progression. Primary objectives were to determine the overall response rate and the toxicities of tivantinib in this patient population. Sixteen patients were enrolled in a two-stage design. Notable grade 3 and 4 hematological adverse events were limited to neutropenia in five and four patients, respectively. Nonhematological adverse events of grade 3 or higher included hypertension (in four patients); syncope, infection, and pain (two each); and fatigue, cough, and pulmonary embolism (one each). Four of 11 evaluable patients (36%) had stable disease as their best response, while the remainder showed disease progression. Overall, tivantinib as a single agent did not show promise for unselected relapsed/refractory myeloma patients. However, the ability to achieve stable disease does suggest that combination regimens incorporating targeted inhibitors in patients with c-MET pathway activation could be of interest.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirrolidinonas / Quinolinas / Proteínas Proto-Oncogénicas c-met / Mieloma Múltiple Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Hematol Asunto de la revista: HEMATOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirrolidinonas / Quinolinas / Proteínas Proto-Oncogénicas c-met / Mieloma Múltiple Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Ann Hematol Asunto de la revista: HEMATOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania