Description
Belinostat is a histone deacetylase (HDAC) inhibitor. HDACs cause the removal of acetyl groups from the lysine residues of histones and other proteins. By inhibiting this enzymatic action, belinostat causes the accumulation of acetylated histones and other proteins within the cells, inducing cell cycle arrest and/or apoptosis of some transformed cells. It is noted that belinostat shows a preferential cytotoxicity towards tumor cells as compared to normal cells.

Policy
Belinostat (Beleodaq) is MEDICALLY NECESSARY for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL). 

Compendial uses that may be considered MEDICALLY NECESSARY include:

• Non-Hodgkins Lymphoma (NHL)
  • Adult T-cell leukemia/lymphoma (ATLL)
  • Mycosis Fungoides (MF)/ Sezary Syndrome (SS)
  • Primary cutaneous CD30+ T cell lymphoproliferative disorders

Belinostat is investigational/unproven therefore is considered NOT MEDICALLY NECESSARY for the treatment of the following hematologic malignancies and solid tumors (not an all-inclusive list) because its effectiveness for these indications has not been established:

• Acute lymphoblastic leukemia
• Acute myeloid leukemia
• Bladder cancer
• Breast cancer
• Chordoma
• Colon cancer
• Fallopian tube cancer
• Hepato-cellular carcinoma
• Lung cancer
• Mesothelioma
• Multiple myeloma
• Myelodysplastic syndrome
• Ovarian cancer
• Pancreatic cancer
• Peritoneal carcinoma
• Prostate cancer
• Rectal cancer
• Thymic tumors
• Thyroid cancer

BlueCross BlueShield of South Carolina recognizes uses and indications of injectable oncology medications (including chemotherapy/systemic therapy, therapeutic radiopharmaceuticals, and selected supportive therapies) to be MEDICALLY NECESSARY if they are listed in the NCCN Drugs and Biologics Compendium with Categories of Evidence + Consensus of 1, 2A and 2B. Treatments listed with a Category of Evidence and Consensus of 3 are considered unproven and NOT MEDICALLY NECESSARY.

Rationale 
Peripheral T-cell lymphomas (PTCLs) comprise a diverse group of rare diseases in which lymph nodes become cancerous. Peripheral T-cell lymphomas represent approximately 10% to 15% of non-Hodgkin’s lymphomas in North America; and these rare malignancies have a poor prognosis. A consequence of lack of randomized controlled trials (RCTs), standard therapy for PTCL has not been established. First-line treatment with anthracycline-based poly-chemotherapy followed by consolidation with high-dose chemotherapy and autologous stem cell transplant in responding patients has demonstrated good feasibility with low toxicity in prospective studies and is widely used in eligible patients. In relapsed and refractory patients, who are not candidates for stem cell transplantations, therapeutic options are limited and are usually palliative. Several new agents are currently under investigation to improve the outcome of PTCL in the first-line and salvage settings. Belinostat, a novel histone deacetylase (HDAC) inhibitor of both class I and class II HDAC enzymes, has demonstrated broad anti-neoplastic activity in pre-clinical studies and promising results in advanced relapsed/refractory lymphomas. 

Reimer and Chawla (2013) reported the case of a 73-year old patient with heavily pre-treated refractory PTCL in complete remission with belinostat for 39 months.

McDermott and Jimeno (2014) stated that several HDAC molecules have been found to be over-expressed in PTCL; and therefore HDAC inhibition has been an important new target in treating these malignancies that have traditionally had poor outcomes and limited treatment response. Phase I studies were tested across a broad range of hematologic malignancies and solid tumors and showed stability of disease with low rates of adverse events. This made it acceptable to proceed with further testing in specific tumor types to further determine effectiveness. Two phase II studies have been completed with belinostat given intravenously in the relapsed/refractory PTCL setting with at least 25 % overall response and minimal toxicities. These findings have led to a request for accelerated approval to the U.S. Food and Drug Administration (FDA) for belinostat in this setting. 

On July 3, 2014, the FDA-approved belinostat (Beleodaq) for the treatment of patients with PTCL; the approval was rendered under the agency’s accelerated approval program.

Belinostat works by inhibiting HDAC enzymes that contribute to T-cells becoming cancerous. It is intended for patients with relapsed or refractory PTCL. The safety and effectiveness of belinostat was evaluated in a clinical study involving 129 patients with relapsed or refractory PTCL. All subjects were treated with belinostat until their disease progressed or side effects became unacceptable. Results showed 25.8% of subjects had achieved complete response (CR) or partial response (PR) after treatment. The most common side effects seen in belinostat-treated participants were anemia, fatigue, fever, nausea and vomiting.

The National Comprehensive Cancer Network's clinical practic guideline on "Non-Hodgkin's Lymphomas" (Version 3.2014) added belinostat as 2nd-line therapy of PTCLs for both candidate and non-candidate for transplant (category 2B recommendation).

Belinostat is a member of HDAC inhibitors that have been tested as a single agent and in combination with other chemotherapies and biological agents in the treatment of solid tumors and other types of hematologic malignancies. However, its effectiveness in these settings has not been established.

Ramalingam and colleagues (2009) conducted a phase II study of belinostat in patients with relapsed malignant pleural mesothelioma. Patients with advanced mesothelioma, progression with 1 prior chemotherapy regimen and Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 were eligible. Belinostat was administered at 1,000 mg/m2 intravenously over 30 minutes on days 1 to 5 of every 3-week cycle. The primary end-point was response rate. The Simon 2-stage design was used. Disease assessments were performed every 2 cycles. A total of 13 patients were enrolled. Baseline characteristics were: median age of 73 years; ECOG performance status 0 (n = 4), 1 (n = 8) and 2 (n = 1). A median of 2 cycles of therapy were administered. Disease stabilization was seen in 2 patients. No objective responses were noted and the study did not meet criteria to proceed to the 2nd stage of accrual. Median survival was 5 months with a median progression-free survival (PFS) of 1 month. Salient toxicities included constipation, emesis, fatigue, and nausea. One patient died as a consequence of cardiac arrhythmia that was deemed “possibly” related to therapy. The authors concluded that belinostat is not active as monotherapy against recurrent malignant pleural mesothelioma. Evaluation of combination strategies or alternate dosing schedules may be necessary for further development of this novel agent in mesothelioma.

In a phase I study, Lassen and co-workers (2010) determined the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumor activity of the combination in solid tumors. Cohorts of 3 to 6 patients were treated with escalating doses of belinostat administered intravenously once-daily, days 1 to 5 q21 days; on day 3, carboplatin (area under the curve (AUC) 5) and/or paclitaxel (175 mg/m2) were administered 2 to 3 hours after the end of the belinostat infusion. In all, 23 patients received 600 to 1,000 mg/m2/day of belinostat with carboplatin and/or paclitaxel. No DLT was observed. The maximal administered dose of belinostat was 1,000 mg/m2/day for days 1 to 5, with paclitaxel (175 mg m(-2)) and carboplatin AUC 5 administered on day 3. Grade III/IV adverse events were (n; %): leucopenia (5; 22%), neutropenia (7; 30%), thrombocytopenia (3; 13%) anemia (1; 4%), peripheral sensory neuropathy (2; 9%), fatigue (1; 4%), vomiting (1; 4%) and myalgia (1; 4%). The pharmacokinetics of belinostat, paclitaxel and carboplatin were unaltered by the concurrent administration. There were 2 PR (1 rectal cancer and 1 pancreatic cancer). A third patient (mixed Mullerian tumor of ovarian origin) showed a complete CA-125 response. In addition, 6 patients showed a stable disease (SD) lasting greater than or equal to 6 months. The authors concluded that the combination was well-tolerated, with no evidence of pharmacokinetic interaction. They stated that further evaluation of anti-tumor activity is needed.

In a phase II study, Mackay et al. (2010) evaluated the activity of belinostat in 2 patient populations: women with metastatic or recurrent platinum resistant (progression within 6 months) epithelial ovarian cancer (EOC) and micropapillary/borderline (LMP) ovarian tumors, both groups had received no more than 3 prior lines of chemotherapy. Belinostat 1,000 mg/m2/day was administered intravenously on days 1 to 5 of a 21-day cycle. Peripheral blood mononuclear cells (PBMCs) and tumor biopsies, where possible, for correlative studies were obtained prior to and following treatment. A total of 18 patients with EOC and 14 patients with LMP tumors were enrolled in this study. Belinostat was well-tolerated with no grade 4 toxicity (179 cycles). Grade 3 toxicity consisted of thrombosis (n = 3), hypersensitivity (n = 1) and elevated ALP (n = 1). One patient with LMP tumor had a PR (unconfirmed) and 10 had SD, 3 were non-evaluable. Median PFS was 13.4 months (95% confidence interval [CI]: 5.6 to not reached). Best response in patients with EOC was SD (9 patients) and median PFS was 2.3 months (95% CI: 1.2 to 5.7 months). An accumulation of acetylated histones H3 and H4 was noted in PBMCs and in tumor tissue. The authors concluded that belinostat is well-tolerated in both patient groups and showed some activity in patients with LMP disease. The clinical effectiveness of belinostat for ovarian cancer awaits results from phase III clinical trials.

In a phase II study, Dizon and associates (2012) evaluated the impact of belinostat in combination with carboplatin in women with platinum-resistant ovarian cancer (including patients with fallopian tube, or primary peritoneal carcinoma). Eligible patients had measurable, recurrent disease within 6 months of their last dose of a platinum-based combination. Belinostat was dosed at 1,000 mg/m2 daily for 5 days with carboplatin AUC 5 on day 3 of 21-day cycles. The primary end-point was overall response rate (ORR), using a 2-stage design. A total of 29 women enrolled in this study and 27 were evaluable. The median number of cycles given was 2 (range of 1 to 10). One patient had a CR and 1 had a PR, for an ORR of 7.4% (95% CI: 0.9% to 24.3%). Twelve patients had SD while 8 had increasing disease. Response could not be assessed in 5 (18.5%). Grade 3 and 4 events occurring in more than 10 % of treated patients were uncommon and limited to neutropenia (22.2%), thrombocytopenia (14.8%), and vomiting (11.1%). The median PFS was 3.3 months and overall survival (OS) was 13.7 months. Progression-free survival of at least 6 months was noted in 29.6% of patients. Due to the lack of drug activity, the study was closed after the first stage. The authors concluded that the addition of belinostat to carboplatin had little activity in a population with platinum-resistant ovarian cancer.

Na and colleagues (2011) investigated the anti-tumor effect of PXD101 (belinostat) combined with irinotecan in colon cancer. HCT116 and HT29 colon cancer cells for cell viability assay were treated with PXD101 and/or SN-38, the active form of irinotecan. Anti-tumor effects of HCT116 and HT29 xenografts treated with these combinations were evaluated. [(18)F]FLT-PET was used to detect early responses to PXD101 and irinotecan in colon cancer. PXD101 and SN38 possessed dose-dependent anti-proliferative activity against HCT116 and HT29 cells and exerted a synergistic effect when used in combination. In xenografted mice, PXD101 in combination with irinotecan dramatically inhibited tumor growth without causing additive toxicity. Apoptotic effects on xenograft tumors were greater with combined treatment than with irinotecan alone. [(18)F]FLT-PET imaging revealed a 64 % decrease in [(18)F]FLT uptake in tumors of HCT116 xenograft-bearing mice treated with a combination of PXD101 and irinotecan, indicating a decrease in thymidine kinase 1 (TK1) activity. These results were supported by Western blot analyses showing a decrease in tumor thymidine kinase 1 protein levels, suggesting that [(18)F]FLT-PET can be used to non-invasively detect early responses to these agents. The authors concluded that these data showed that PXD101 (belinostat) increased the cytotoxic activity of irinotecan in in-vitro and in-vivo colon cancer models and suggested these agent combinations should be explored in the treatment of colon cancer.

In a phase II clinical trial, Giaccone and colleagues (2011) examined the effectiveness of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors. Patients with advanced thymic epithelial malignancies in whom at least 1 line of platinum-containing chemotherapy had failed were eligible for this study. Other eligibility criteria included adequate organ function and good performance status. Belinostat was administered intravenously at 1 g/m2 on days 1 to 5 of a 21-day cycle until disease progression or development of intolerance. The primary objective was response rate in patients with thymoma. Of the 41 patients enrolled, 25 had thymoma, and 16 had thymic carcinoma; patients had a median of 2 previous systemic regimens (range of 1 to 10 regimens). Treatment was well-tolerated, with nausea, vomiting, and fatigue being the most frequent adverse effects. Two patients achieved PR (both had thymoma; response rate, 8%; 95% CI: 2.2% to 25%), 25 had SD, and 13 had progressive disease; there were no responses among patients with thymic carcinoma. Median times to progression and survival were 5.8 and 19.1 months, respectively. Survival of patients with thymoma was significantly longer than that of patients with thymic carcinoma (median not reached versus 12.4 months; p = 0.001). Protein acetylation, regulatory T-cell numbers, and circulating angiogenic factors did not predict outcome. The authors concluded that belinostat has modest anti-tumor activity in this group of heavily pre-treated thymic malignancies. However, the duration of response and disease stabilization is intriguing, and additional testing of belinostat in this disease is warranted.

Yeo and colleagues (2012) noted that epigenetic aberrations have been reported in hepato-cellular carcinoma (HCC). In a phase I/II clinical trial, these researchers determined dose-limiting toxicity (DLT) and MTD of belinostat for patients with unresectable HCC. They assessed pharmacokinetics (phase I study), and assessed activity of and explored potential biomarkers for response (phase II study). Major eligibility criteria included histologically confirmed unresectable HCC, ECOG performance score less than or equal to 2, and adequate organ function. Phase I consisted of 18 patients; belinostat was given intravenously once-daily on days 1 to 5 every 3 weeks; dose levels were 600 mg/m2 per day (level 1), 900 mg/m2 per day (level 2), 1,200 mg/m2 per day (level 3), and 1,400 mg/m2 per day (level 4). Phase II consisted of 42 patients. The primary end-point was PFS, and the main secondary end-points were response according to Response Evaluation Criteria in Solid Tumors (RECIST) and OS. Exploratory analysis was conducted on pre-treatment tumor tissues to determine whether HR23B expression is a potential biomarker for response. Belinostat pharmacokinetics were linear from 600 to 1,400 mg/m2 without significant accumulation. The MTD was not reached at the maximum dose administered. Dose level 4 was used in phase II. The median number of cycles was 2 (range of 1 to 12). The PR and SD rates were 2.4 % and 45.2 %, respectively. The median PFS and OS were 2.64 and 6.60 months, respectively. Exploratory analysis revealed that disease stabilization rate (CR plus PR plus SD) in tumors having high and low HR23B histo-scores were 58% and 14%, respectively (p = 0.036). The authors concluded that epigenetic therapy with belinostat demonstrated tumor stabilization and is generally well-tolerated. HR23B expression was associated with disease stabilization. The clinical effectiveness of belinostat for HCC awaits results from phase III clinical trials.

Ismaili and coworkers (2012) stated that targeting both vascular endothelial growth factor and fibroblast growth factor pathways is a very promising strategy. In bladder (urothelial) cancer, 2 molecules are promising, the belinostat and the bortezomib.

Lin and associates (2013) evaluated the therapeutic effects of the histone deacetylase inhibitor PXD101 (belinostat) alone and in combination with conventional chemotherapy in treating thyroid cancer. These researchers studied 8 cell lines from 4 types of thyroid cancer (papillary, follicular, anaplastic and medullary). The cytotoxicity of PXD101 alone and in combination with 3 conventional chemotherapeutic agents (doxorubicin, paclitaxel and docetaxel) was measured using LDH assay. Western blot assessed expression of acetylation of histone H3, histone H4 and tubulin, proteins associated with apoptosis, RAS/RAF/ERK and PI3K/AKT/mTOR signaling pathways, DNA damage and repair. Apoptosis and intra-cellular reactive oxygen species (ROS) were measured by flow cytometry. Mice bearing flank anaplastic thyroid cancers (ATC) were daily treated with intra-peritoneal injection of PXD101 for 5 days/week. PXD101 effectively inhibited thyroid cancer cell proliferation in a dose-dependent manner. PXD101 induced ROS accumulation and inhibited RAS/RAF/ERK and PI3K/mTOR pathways in sensitive cells. Double-stranded DNA damage and apoptosis were induced by PXD101 in both sensitive and resistant cell lines. PXD101 retarded growth of 8505C ATC xenograft tumors with promising safety. Combination therapy of PXD101with doxorubicin and paclitaxel demonstrated synergistic effects against 4 ATC lines in vitro. The authors concluded that PXD101 repressed thyroid cancer proliferation and has synergistic effects in combination with doxorubicin and paclitaxel in treating ATC. The authors stated that these findings supported clinical trials using PXD101 for patients with this dismal disease.

Scheipl et al. (2013) noted that chordomas are rare malignancies of the axial skeleton. Therapy is mainly restricted to surgery. These researchers investigated HDAC inhibitors as potential therapeutics for chordomas. Immunohistochemistry (IHC) was performed using the HDAC 1 – 6 antibodies on 50 chordoma samples (34 primary tumors, 16 recurrences) from 44 patients (27 males, 17 females). Pan-HDAC-inhibitors vorinostat (SAHA), panobinostat (LBH-589), and belinostat (PXD101) were tested for their effectiveness in the chordoma cell line MUG-Chor1 via Western blot, cell cycle analysis, caspase 3/7 activity (MUG-Chor1, UCh-1), cleaved caspase-3, and PARP cleavage; p-values below 0.05 were considered significant. Immunohistochemistry was negative for HDAC1, positive for HDAC2 in most (n = 36; 72%), and for HDACs 3 to 6 in all specimens available (n = 43; 86 %); HDAC6 expression was strongest. Vorinostat and panobinostat, but not belinostat caused a significant increase of G2/M phase cells and of cleaved caspase-3 (p = 0.0003, and p = 0.0014 after 72 hours, respectively), and a peak of caspase 3/7 activity. PARP cleavage confirmed apoptosis. The presented chordoma series expressed HDACs 2 – 6 with strongest expression of HDAC6. The authors concluded that vorinostat and panobinostat significantly increased apoptosis and changed cell cycle distribution in-vitro. They stated that HDAC-inhibitors should be further evaluated as therapeutic options for chordoma.

Dai et al. (2011) investigated interactions between belinostat and bortezomib in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) cells. Co-administration of sub-micromolar concentrations of belinostat with low nanomolar concentrations of bortezomib sharply increased apoptosis in both AML and ALL cell lines and primary blasts. Synergistic interactions were associated with interruption of both canonical and non-canonical nuclear factor (NF)-κB signaling pathways, e.g., accumulation of the phosphorylated (S32/S36) form of IκBα, diminished belinostat-mediated RelA/p65 hyper-acetylation (K310), and reduced processing of p100 into p52. These events were accompanied by down-regulation of NF-κB-dependent pro-survival proteins (e.g., XIAP, Bcl-xL). Moreover, belinostat/bortezomib co-exposure induced up-regulation of the BH3-only pro-death protein Bim. Significantly, shRNA knock-down of Bim substantially reduced the lethality of belinostat/bortezomib regimens. Administration of belinostat ± bortezomib also induced hyper-acetylation (K40) of α-tubulin, indicating histone deacetylase inhibitor 6 inhibition. Finally, in contrast to the pronounced lethality of belinostat/bortezomib toward primary leukemia blasts, equivalent treatment was relatively non-toxic to normal CD34(+) cells. The authors concluded that these findings indicated that belinostat and bortezomib interact synergistically in both cultured and primary AML and ALL cells, and raise the possibilities that up-regulation of Bim and interference with NF-κB pathways contribute to this phenomenon. They also suggested that combined belinostat/bortezomib regimens warrant further attention in acute leukemia.

In a phase II, multi-center study, Cashen et al. (2012) estimated the effectiveness of belinostat for the treatment of myelodysplastic syndrome (MDS). Adults with MDS and less than or equal to 2 prior therapies were treated with belinostat 1,000 mg/m2 intravenously on days 1 to 5 of a 21-day cycle. The primary end-point was a proportion of confirmed responses during the first 12 weeks of treatment. Responding patients could receive additional cycles until disease progression or unacceptable toxicity. A total of 21 patients were enrolled, and all were evaluable. Patients were a median 13.4 months from diagnosis, and 14 patients (67%) had less than 5 % bone marrow blasts. Seventeen patients (81%) were transfusion-dependent. Prior therapy included azacytidine (n = 7) and chemotherapy (n = 8). The patients were treated with a median of 4 cycles (range of 1 to 8) of belinostat. There was 1 confirmed response-hematologic improvement in neutrophils-for an ORR of 5% (95% CI: 0.2 to 23). Median OS was 17.9 months. Grades 3 to 4 toxicities considered at least to be possibly related to belinostat were: neutropenia (n = 10), thrombocytopenia (n = 9), anemia (n = 5), fatigue (n = 2), febrile neutropenia (n = 1), headache (n = 1), and QTc prolongation (n = 1). Because the study met the stopping rule in the first stage of enrollment, it was closed to further accrual.

Grassadonia et al. (2013) stated that hydroxamate-based HDAC inhibitors (Hb-HDACIs), such as vorinostat, belinostat and panobinostat, have been previously shown to have a wide range of activity in hematologic malignancies such as cutaneous T-cell lymphoma and multiple myeloma. Recent data showed that they synergize with a variety of cytotoxic and molecular targeted agents in many different solid tumors, including breast, prostate, pancreatic, lung and ovarian cancer. Hb-HDACIs have a quite good toxicity profile and are now being tested in phase I and II clinical trials in solid tumors with promising results in selected neoplasms, such as HCC.

Kirschbaum et al. (2014) performed a phase II study of belinostat in patients with acute myeloid leukemia (AML). In this open-label phase II study, patients with relapsed/refractory AML, or newly diagnosed patients with AML over the age of 60, were eligible. Belinostat was administered intravenously at a dose of 1,000 mg/m2 daily on days 1 to 5 of a 21-day cycle until progression or unacceptable toxicity. The primary end-point was CR rate, with secondary end-points of ORR (CR + PR), time to treatment failure, OS and safety. A total of 12 eligible patients with AML were enrolled, of whom 6 had received at least 1 prior line of therapy. No CR or PR was seen; 4 patients had SD for at least 5 cycles. Grade 3 non-hematological toxicities occurred in 4 patients. The authors concluded that belinostat as monotherapy has minimal single-agent effect in AML on this dosing schedule.

References 

1. Ramalingam SS, Belani CP, Ruel C, et al. Phase II study of belinostat (PXD101), a histone deacetylase inhibitor, for second line therapy of advanced malignant pleural mesothelioma. J Thorac Oncol. 2009;4(1):97-101.
2. Lassen U, Molife LR, Sorensen M, et al. A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours. Br J Cancer. 2010;103(1):12-17.
3. Mackay HJ, Hirte H, Colgan T, et al. Phase II trial of the histone deacetylase inhibitor belinostat in women with platinum resistant epithelial ovarian cancer and micropapillary (LMP) ovarian tumours. Eur J Cancer. 2010;46(9):1573-1579.
4. Na YS, Jung KA, Kim SM, et al. The histone deacetylase inhibitor PXD101 increases the efficacy of irinotecan in in vitro and in vivo colon cancer models. Cancer Chemother Pharmacol. 2011;68(2):389-398.
5. Giaccone G, Rajan A, Berman A, et al. Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors. J Clin Oncol. 2011;29(15):2052-2059.
6. Dai Y, Chen S, Wang L, et al. Bortezomib interacts synergistically with belinostat in human acute myeloid leukaemia and acute lymphoblastic leukaemia cells in association with perturbations in NF-κB and Bim. Br J Haematol. 2011;153(2):222-235.
7. Dizon DS, Blessing JA, Penson RT, et al. A phase II evaluation of belinostat and carboplatin in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol. 2012;125(2):367-371.
8. Yeo W, Chung HC, Chan SL, et al.  Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: A multicenter phase I/II study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group. J Clin Oncol. 2012;30(27):3361-3367.
9. Ismaili N, Afqir S, Belbaraka R, et al. Urological cancers: ECCO/ESMO congress 2011. Presse Med. 2012;41(12 Pt 1):1181-1187.
10. Cashen A, Juckett M, Jumonville A, et al. Phase II study of the histone deacetylase inhibitor belinostat (PXD101) for the treatment of myelodysplastic syndrome (MDS). Ann Hematol. 2012;91(1):33-38.
11. Lin SF, Lin JD, Chou TC, et al. Utility of a histone deacetylase inhibitor (PXD101) for thyroid cancer treatment. PLoS One. 2013;8(10):e77684.
12. Scheipl S, Lohberger B, Rinner B, et al. Histone deacetylase inhibitors as potential therapeutic approaches for chordoma: An immunohistochemical and functional analysis. J Orthop Res. 2013;31(12):1999-2005.
13. Grassadonia A, Cioffi P, Simiele F, et al. Role of hydroxamate-based histone deacetylase inhibitors (Hb-HDACIs) in the treatment of solid malignancies. Cancers (Basel). 2013;5(3):919-942.
14. Reimer P, Chawla S. Long-term complete remission with belinostat in a patient with chemotherapy refractory peripheral T-cell lymphoma. J Hematol Oncol. 2013;6:69.
15. McDermott J, Jimeno A. Belinostat for the treatment of peripheral T-cell lymphomas. Drugs Today (Barc). 2014;50(5):337-345.
16. U.S. Food and Drug Administration. FDA approves Beleodaq to treat rare, aggressive form of non-Hodgkin lymphoma. July 3. 12014. FDA: Silver Spring, MD. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm403929.htm. Accessed July 11, 2014.
17. No authors listed. Highlights of Prescribing Information. Beleodaq® (belinostat) for injection, for intravenous administration. Spectrum Pharmaceuticals, Inc., Irvine, CA. July 2014. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206256lbl.pdf. Accessed July 11, 2014.
18. National Comprehensive Cancer Network. Clinical practice guideline: Non-Hodgkin’s Lymphomas. Version 3.2014. NCCN: Fort Washington, PA.
19. Kirschbaum MH, Foon KA, Frankel P, et al. A phase 2 study of belinostat (PXD101) in patients with relapsed or refractory acute myeloid leukemia or patients over the age of 60 with newly diagnosed acute myeloid leukemia: A California Cancer Consortium Study. Leuk Lymphoma. 2014;55(10):2301-2304.

Coding Section 

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

Dosage Information 
BELEODAQ* (belinostat) for injection, for intravenous administration
Initial U.S. Approval: 2014

Indications and Usage
Beleodaq is a histone deacetylas inhibitor indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This indication is approved under accelerated approval based on tumor response rate and duration of response. An improvement in survival or disease-related symptoms has not been established. continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial. 

Dosage and Administration 
Recommended dosage of Beleodaq is 1,000 mg/m² administered over 30 minutes by intravenous infusion once daily on days 1 – 5 of a 21 day cycle. Cycles can be repeated until disease progression or unacceptable toxicity.

Treatment dicontinuation or interuption with or without dosage reduction by 25% may be nned to manage adverse reaction.

Dosage Forms and Strengths
For injection 500 mg, lyophilized powder in single use vial for reconstitution

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology^© American Medical Association. All Rights Reserved." 

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