Cancer Treatment Today » Hodgkin’s

Everolimus for Hodgkin’s – pro

M Levin, MD — Tue, 12 Mar 2013 03:24:38 +0000

Everolimus is an oral antineoplastic agent that targets the raptor mammalian target of rapamycin (mTORC1). The phosphatidylinositol 3-kinase/mTOR signal transduction pathway has been demonstrated to be activated in Hodgkin lymphoma (HL) and there was speculation that everolimus might be effective for this disease. Johnston et al studied everolimus in 19 patient. Patients had received a median of six prior therapies (range, 3-14) and 84% had undergone prior autologous stem cell transplant. The ORR was 47% (95% CI: 24-71%) with eight patients achieving a PR and one patient achieving a CR. The median TTP was 7.2 months. Four responders remained progression free at 12 months. IN what appears a continuation fo this study, Johnston fartehr presented 57 patients and concluded that everolimus monotherapy demonstrated favorable efficacy and a short time to response in patients with heavily pretreated, relapsed/refractory classical HL. Several studies of combinations with everolimus for Hodgkin’s are listed on clinicaltrials.gov. There is also the study: Study of RAD001 in Patients With Relapsed/Refractory Hodgkin Lymphoma That Has Progressed After High-dose Chemotherapy and Autologous Stem Cell Transplant and/or After Gemcitabine- or Vinorelbine- or Vinblastine- Based Treatment, NCT01022996.

Rule S. Everolimus in relapsed Hodgkin’s lymphoma: something exciting or a case of caveat mTOR? Am J Hematol. 2010 May; 85(5):313-4.

Johnston PB, Inwards DJ, Colgan JP, Laplant BR, Kabat BF, Habermann TM, Micallef IN, Porrata LF, Ansell SM, Reeder CB, Roy V, Witzig TE.
A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma.Am J Hematol. 2010 May;85(5):320-4.

2740 Everolimus for Relapsed/Refractory Classical Hodgkin Lymphoma: Multicenter, Open-Label, Single-Arm, Phase 2 Study
Program: Oral and Poster Abstracts
Session: 624. Lymphoma – Therapy with Biologic Agents, excluding Pre-Clinical Models: Poster II
Patrick B. Johnston

Ibeas P, Cantos B, Provencio M. mTOR inhibitor in the treatment of Hodgkin’s lymphoma: a case report Blood and Lymphatic Cancer: Targets and Therapy November 2011 Volume 2011:1 Pages 19 – 22

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Zolinza for Hodgkin’s

M Levin, MD — Fri, 01 Mar 2013 21:03:38 +0000

Current chemotherapy drugs are very effective for Hodgkin’s lymphomas but patients who relapse after receiving them don;t do as well. This is because the cancers develop resistance to the se drugs. Zolinza is a new drug approved in the USA for the treatment of cutaneous(skin) T-cell lymphoma who have progressive, persistent or recurrent disease or following two systemic therapies. It may be effective for Hodgkin’s. For Hodgkin’s, a phase II study enrolled twenty-five eligible patients. The overall resposne rate was low, 4% (one partial response), but the drug was well tolerated. A phase I clinical trial treated several types of lymphoma. The best responses were seen in those with Hodgkin and diffuse large B-cell lymphoma (Budde et al). A study of Vorinostat and Lenalidomide in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma was started at the City of Hope but was terminated.

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Vorinostat for Hodgkin’s – pro

M Levin, MD — Fri, 01 Mar 2013 19:23:16 +0000

Current front-line chemotherapy drugs are very effective against Hodgkin’s lymphoma but patients who relapse after receiving them are less likely to achieve long-term, disease-free survival with current salvage therapies. This is because Hodgkin’s develops resistance to the drugs or the tumor’s biology changes in some way to reduce their effectiveness. This led to researchers testing newly released drugs for this purpose. Zolinza is approved in the USA for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. However, it may be effective in other conditions as well. Merck initiated phase II studies, VANTAGE 088 and VANTAGE 095, as well as a Phase III, global, randomized, double-blind, placebo-controlled, 742-patient multicenter trial investigating Zolinza plus Velcade in relapsed MM after one to three prior anti-myeloma. However, the therapy remains investigational so far. For Hodgkin’s, a phase II study enrolled twenty-five eligible patients The ORR was 4% (one partial response). Median PFS was 4.8 months and the drug was well tolerated. A phase I clinical trial tested the effectiveness of HDACs to augment standard chemotherapy. Patients treated in the trial had several types of lymphoma. The best responses were seen in those with Hodgkin and diffuse large B-cell lymphoma (Budde et al). A study of Vorinostat and Lenalidomide in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma was started at the City of Hope but was terminated.

Weber D, Badros AZ, Jagannath S, et al. Vorinostat plus bortezomib for the treatment of relapsed/refractory multiple myeloma: Early clinical experience. Blood. 2008;112:322, abstract number 871

Kirschbaum MH, Goldman BH, Zain JM, Cook JR, Rimsza LM, Forman SJ, Fisher R, A phase 2 study of vorinostat for treatment of relapsed or refractory Hodgkin lymphoma: Southwest Oncology Group Study S0517. .Leuk Lymphoma. 2012 Feb;53(2):259-62.

Budde LE, Zhang MM, Shustov AR, Pagel JM, Gooley TA, Oliveira GR, Chen TL, Knudsen NL, Roden JE, Kammerer BE, Frayo SL, Warr TA, Boyd TE, Press OW, Gopal AK.
A phase I study of pulse high-dose vorinostat (V) plus rituximab (R), ifosphamide, carboplatin, and etoposide (ICE) in patients with relapsed lymphoma.Br J Haematol. 2013 Jan 29. doi: 10.1111/bjh.12230.

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Zolinza for myeloma here