Cancer Treatment Today » Chemotherapy

Adcetris – pro

M Levin, MD — Sun, 06 Oct 2013 23:48:08 +0000

The Food and Drug Administration (FDA) has approved Adcetris (brentuximab vedotin) for treating patients with Hodgkin lymphoma who have already had a stem cell transplant or are not eligible for one. The drug was also approved for patients with systemic anaplastic large-cell lymphoma (ALCL), who have not improved with at least one previous therapy. Adcetris is a newer type of drug known as an antibody-drug conjugate: a manmade antibody that targets a molecule found on some lymphoma cells, combined with a chemotherapy drug. The antibody acts as a sort of homing signal to bring the chemo drug directly to the lymphoma cells.

n a 2010 trial34% of patients with refractory Hodgkin Lymphoma achieved complete remission and another 40% had partial remission.Tumor reductions were achieved in 94% of patients. In ALCL, 87% of patients had tumors shrink at least 50% and 97% of patients had some tumor shrinkage. There are no published studies of this drug in and for first line therapy.

NCT00848926 – A Pivotal Open-Label Trial of Brentuximab Vedotin for Hodgkin Lymphoma

Cytotoxic Agents | ADC Review / Journal of Antibody-drug Conjugates, May 23, 2013 [6]

Prescribing Information,(US)/Adcetris (brentuximab vedotin) for Injection (2013)

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

For Lay version see here

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.

For Lay version see here.

Zolinza for myeloma here

GDP(Gemcitabine, platin, dexamethasone) for salvage of Hodgkin’s – pro

M Levin, MD — Wed, 13 Feb 2013 19:49:13 +0000

Relapsed or refractory Hodgkin lymphoma is a challenging problem for clinicians who treat hematologic malignancies. The general approach involves salvage chemo and a consideration of stem cell transplantation, if salvage succeeds. Unfortunately, there are no direct comparisons of different salvage combinations and no consensus on the gold-standard second-line chemotherapy. The published randomized controlled trials (RCTs) of ASCT for RR-HL used mini-BEAM (ie, BCNU [bis-chloronitrosourea], etoposide, ara-C, melphalan) or dexa-BEAM (dexamethasone, BCNU, etopoxide, ara-C, melphalan), so some experts think that these regimens should be considered standard regimens in this setting(2). Gemzar/cisplatin/dexamethasone in patients with relapsed Hodgkin’s lymphoma was published in 2003 by Baez et al(1). The trial included 23 patients and overall response rate was nearly 70%; the remaining 30% of patients achieved disease stabilization. No patient experienced progressive disease while being treated with Gemzar/cisplatin/dexamethasone. Toxicity was mild and all patients were able to undergo a subsequent autologous stem cell transplant. NCCN(3) is more liberal and lists GDP (gemcitabine, carboplatin and dexamethasone)as well as other regimesn based solely on phase II studies.

1.Baetz T, Belch A, Couban S, et al. Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin’s disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group. Annals of Oncology. 2003;14:1762-1767.

2.John Kuruvilla, Armand Keating, and Michael Crump, How I treat relapsed and refractory Hodgkin lymphoma Blood (2011) 117(16): 4208-4217

3.NCCN, HODG-E, 2

For Lay version see here

Rituxan and Rituxan with Gemcitabine for Hodgkin’s Disease – pro

M Levin, MD — Thu, 09 Aug 2012 17:58:00 +0000

According to results recently published in the journal Blood, Rituxan® (rituximab) appears to be a promising agent in the treatment of some patients with recurrent Hodgkin’s. Rituxan® is a monoclonal antibody approved for treatment of non-Hodgkin’s lymphoma (NHL) and binds to an antigen called CD 20. A small subset of patients with Hodgkin’s lymphoma (3% to 8%) has a type of cancer called CD 20 lymphocyte predominant Hodgkin’s lymphoma, characterized by a large proportion of their cancer cells expressing CD 20. Patients with CD 20 lymphocyte predominant Hodgkin’s lymphoma tend to have a higher rate of recurrence following standard therapy than other patients with Hodgkin’s lymphoma.

NCCN on p HODG-E says that Rituxan should be considered for all patients with relapsed Hodgkin’s disease. It recommends it with ABVD for Lymphocyte Predominant Hodgkin’s in first line. It does not address other chemo combinations with Rituxan.

Gemcitabine has also been combined with Rituxin and with rituximab and other drugs in studies for relapsed Hodgkin’s. These two drugs together in several phase II studies appear to be “mildly” active and well tolerated.

D. Re, R. K. Thomas, K. Behringer, and V. Diehl
From Hodgkin disease to Hodgkin lymphoma: biologic insights and therapeutic potential
Blood, June 15, 2005; 105(12): 4553 – 4560.

Yasuhiro Oki MD, Barbara Pro MD et al, study of gemcitabine in combination with rituximab in patients with recurrent or refractory Hodgkin lymphoma†
Cancer Volume 112, Issue 4, pages 831–836, 15 February 2008

Oki Y, Younes A. Does rituximab have a place in treating classic hodgkin lymphoma?Curr Hematol Malig Rep. 2010 Jul;5(3):135-9

P. Validire, C. Fermé, P. Brice, M. Diviné, J. Gabarre, K. Bouabdallah, O. Fitoussi, D. Chaoui, C. Soussain, P. Carde, D. Decaudin A large multicentric study of gemcitabine-based regimen in relapsed or refractory Hodgkin lymphoma (HL) patients (pts). Print this page
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 18518

Read the Layperson version here.

BEACOPP and ABVD for Hodgkin’s – pro

M Levin, MD — Thu, 21 Jun 2012 18:10:25 +0000

MOPP, developed in the mid 1960′s, was the first combination chemotherapy regimen for treating Hodgkin’s lymphoma (disease) with a high success rate. It has been used alone or in combination (in part or total) with ABVD chemotherapy. Studies over the last few years seem to indicate ABVD is just as effective with fewer long term effects.The most widely accepted regimen for HD patients with advanced stage now is ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). To improve on these results, time and/or dose intensified third-line protocols were investigated. Such a protocol developed by the German Hodgkin’s Lymphoma Study Group (GHSG), BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) has been studied in various patient groups. THe results appear no better than with ABVD but also not worse.The HD9 randomized trial compared COPP/ABVD + RT with standard dose BEACOPP + RT and escalated dose BEACOPP + RT. Irradiation was given to approximately 70% of patients on all three arms based on presence of initial moderately bulky (> 5 cm) or residual nodal abnormalities. The most recent analysis, also with a median follow-up of 6.9 years, included 1195 evaluable patients and demonstrated superior freedom from treatment failure and overall survival for the patients treated with escalated dose BEACOPP + RT (Table 5).31,32 Escalated BEACOPP showed a higher but manageable rate of hematologic toxicity. Longer follow-up will be required to determine the true usefulness of escalated BEACOPP + RT. Whether the increased toxicity of this regimen (3% treatment induced mortality, 100% infertility in men, 100% infertility plus premature menopause in most women over the age of 25, increased risk of second neoplasms) can be justified remains to be determined. Of particular note is the fact that the increased efficacy of escalated BEACOPP only translated into a survival benefit in the 20% of patients with the poorest prognosis at diagnosis. The other 80% of patients with advanced Hodgkin lymphoma had the same overall survival whether initially treated with ABVD or escalated BEACOPP because of the availability of effective secondary treatment with high-dose chemotherapy and stem cell transplantation.

Bonadonna, M.D., and Alessandro M. Gianni, M.D., for the Michelangelo Foundation, the Gruppo Italiano di Terapie Innovative nei Linfomi, and the Intergruppo Italiano Linfomi
ABVD versus BEACOPP for Hodgkin’s Lymphoma When High-Dose Salvage Is Planned.
N Engl J Med 2011; 365:203-212July 21, 2011

.Filatova, LV et al, [Effectiveness and toxicity of MOPP, ABVD, BEACOPP chemotherapy in first-diagnosed Hodgkin lymphoma with a poor prognosis].Vopr Onkol. 2013;59(2):59-65
[Filatova LV, Plotnikova AA, Gershanovich ML, Semiglazova TIu.

Das P, Ng A, Constine LS, Hodgson DC, Mendenhall NP, Morris DE, Yunes MJ, Chauvenet AR, Friedberg JE, Hudson MM, Winter JN, Expert Panel on Radiation Oncology-Hodgkin's Lymphoma. ACR Appropriateness Criteria® Hodgkin's lymphoma--favorable prognosis stage I and II. [online publication]. Reston (VA): American College of Radiology (ACR); 2008. 14 p. [53 references]