Your browser doesn't support javascript.
loading
Panobinostat in combination with bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma: an open-label, multicentre phase 2 trial.
Tan, Daryl; Phipps, Colin; Hwang, William Y K; Tan, Soo Yong; Yeap, Chun Hsien; Chan, Yiong Huak; Tay, Kevin; Lim, Soon Thye; Lee, Yuh Shan; Kumar, Sathish Gopalakrishnan; Ng, Soo Chin; Fadilah, S; Kim, Won Seog; Goh, Yeow Tee.
Afiliación
  • Tan D; Department of Hematology, Singapore General Hospital, Singapore; Raffles Cancer Centre, Raffles Hospital, Singapore.
  • Phipps C; Department of Hematology, Singapore General Hospital, Singapore.
  • Hwang WY; Department of Hematology, Singapore General Hospital, Singapore.
  • Tan SY; Department of Pathology, Singapore General Hospital, Singapore.
  • Yeap CH; Department of Hematology, Singapore General Hospital, Singapore.
  • Chan YH; Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Tay K; Medical Oncology, National Cancer Centre of Singapore, Singapore.
  • Lim ST; Medical Oncology, National Cancer Centre of Singapore, Singapore.
  • Lee YS; Department of Hematology, Singapore General Hospital, Singapore.
  • Kumar SG; Department of Hematology, Singapore General Hospital, Singapore.
  • Ng SC; Sime Darby Medical Centre, Selangor, Malaysia.
  • Fadilah S; Hospital Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
  • Kim WS; Samsung Medical Centre, Seoul, South Korea.
  • Goh YT; Department of Hematology, Singapore General Hospital, Singapore. Electronic address: goh.yeow.tee@sgh.com.sg.
Lancet Haematol ; 2(8): e326-33, 2015 Aug.
Article en En | MEDLINE | ID: mdl-26688485
BACKGROUND: Patients with relapsed or refractory peripheral T-cell lymphoma have a poor prognosis after conventional chemotherapy. Approved novel agents have only modest single-agent activity in most subtypes of peripheral T-cell lymphoma. Panobinostat is a potent oral pan-deacetylase inhibitor. Findings of many preclinical studies have shown synergistic antilymphoma activity when panobinostat is combined with the proteasome inhibitor bortezomib. We aimed to study the effect of panobinostat and bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma. METHODS: In this open-label, multicentre phase 2 trial, we recruited patients aged 21 years or older with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy from five tertiary hospitals in Singapore, Malaysia, and South Korea. Patients received 20 mg oral panobinostat three times a week and 1·3 mg/m(2) intravenous bortezomib two times a week, both for 2 of 3 weeks for up to eight cycles. The primary endpoint was the proportion of patients who achieved an objective response in accordance with the International Working Group revised response criteria; analyses were by intention to treat. The study is completed and is registered with ClinicalTrials.gov, number NCT00901147. FINDINGS: Between Nov 9, 2009, and Nov 26, 2013, we enrolled 25 patients with various histological subtypes of peripheral T-cell lymphoma. Of 23 patients assessable for responses, ten (43%, 95% CI 23-63) patients had an objective response, of which five were complete responses. Serious adverse events were reported in ten (40%) of 25 patients. Common treatment-related grade 3-4 adverse events included thrombocytopenia (17 [68%]), neutropenia (ten [40%]), diarrhoea (five [20%]), and asthenia or fatigue (two [8%]). We recorded peripheral neuropathy of any grade in ten (40%) patients. INTERPRETATION: Combined proteasome and histone deacetylase inhibition is safe and feasible and shows encouraging activity for patients with peripheral T-cell lymphoma. Our findings validate those of preclinical studies showing synergism in the combination and represent a rational way forward in harnessing the full potential of novel agents in peripheral T-cell lymphoma. FUNDING: Novartis Pharmaceuticals, Janssen Pharmaceuticals, and Singhealth Foundation.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma de Células T Periférico / Bortezomib / Ácidos Hidroxámicos / Indoles / Antineoplásicos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: Lancet Haematol Año: 2015 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma de Células T Periférico / Bortezomib / Ácidos Hidroxámicos / Indoles / Antineoplásicos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: Lancet Haematol Año: 2015 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Reino Unido