Zolinza for maintenance in glioblastoma

M Levin, MD — Mon, 13 May 2013 12:40:37 +0000

With the advent of biologic therapies, many new avenues to approach recalcitrant and difficult diseases have emerged. Once such cancer is the brain cancer glioblastoma(GBM). It is tempting to use Zolinza(vorinostate) for maintenance after attaining a remission of glioblastoma, because this is a disease that almost always comes back.

Unfortunately, there is as of yet no literature supporting the use of Zolnza for maintenance for gliolastoma. A recent study for recurrent disease by Galanis et al concluded that vorinostat monotherapy is well tolerated in patients with recurrent GBM and has modest single-agent activity. Histone acetylation analysis and RNA expression profiling, sophisticated wyas to look at what this drug is doing to the cancer cells, indicate that vorinostat in this dose and schedule affects target pathways in GBM. Additional testing of vorinostat in combination regimens is warranted.

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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

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Zolinza for maintenance in glioblastoma

Vorinostat for Hodgkin’s – pro