belinostat

belinostat

(be-lin-o-stat),

Beleodaq

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: temporary class
Pregnancy Category: D

Indications

Treatment of relapsed/refractory peripheral T-cell lymphoma (PTCL).

Action

Acts as a histone deacetylase (HDAC) inhibitor, produces accumulation of acetylated histones and other proteins resulting in cell cycle arrest/apoptosis of cells; may have affinity for tumor cells.

Therapeutic effects

Decreased spread of relapsed/refractory PCTL.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Distributes into total body water, minimal tissue distribution; crosses the placenta.
Metabolism and Excretion: Rapidly and extensively metabolized by the liver, primarily by the UGT1A1 enzyme system with minor metabolism by other systems, <2% excreted unchanged in urine.
Half-life: 1.1 hr.

Time/action profile (response)

ROUTEONSETPEAKDURATION
IVunknownunknown12 mo

Contraindications/Precautions

Contraindicated in: Concurrent use of strong inhibitors of UGT1A1; Obstetric: Pregnancy should be avoided (may cause fetal harm); Lactation: Breastfeeding should be avoided.
Use Cautiously in: Advanced stage disease/large tumor burden (↑ risk of Tumor Lysis Syndrome); genetic implication Patients with UGT1A1*28 polymorphism (initial dose reduction required); Moderate/severe hepatic impairment or CCr <39 mL/min; Obstetric: Women with child-bearing potential (reliable contraception recommended); Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)
  • dizziness
  • headache

Respiratory

  • cough

Cardiovascular

  • hypotension
  • peripheral edema
  • phlebitis

Gastrointestinal

  • hepatotoxicity (life-threatening)
  • nausea (most frequent)
  • vomiting (most frequent)
  • abdominal pain
  • ↓ appetite
  • constipation
  • diarrhea

Genitourinary

  • ↑ creatinine

Dermatologic

  • pruritus
  • rash

Fluid and Electrolyte

  • hypokalemia

Hematologic

  • anemia (life-threatening)
  • leukopenia
  • thrombocytopenia (life-threatening)

Local

  • infusion site pain

Miscellaneous

  • infestion (life-threatening)
  • sepsis (life-threatening)
  • tumor lysis syndrome
  • chills (most frequent)
  • fever

Interactions

Drug-Drug interaction

Concurrent use of strong inhibitors of UGT1A1 including atazanvir, gemfibrozil, and indinavir may ↑ blood levels and risk of serious toxicity and should be avoided.

Route/Dosage

Intravenous (Adults) 1000 mg/m2/day on days 1–5 of a 21-day cycle. Cycle may be repeated until disease progression or unacceptable toxicity. Patients with UGT1A1*28 polymorphism—750 mg/m2 initial dose.

Availability

Lyophilized powder for intravenous injection (requires reconstitution): 500 mg/vial

Nursing implications

Nursing assessment

  • Monitor for signs and symptoms of infections (fever, chills, dyspnea, cough). Do not administer belinostat in patients with active infections.
  • Assess for signs and symptoms of tumor lysis syndrome in patients with advanced stage disease and/or with high tumor burden.
  • Monitor for nausea, vomiting, and diarrhea. May require antiemetics and antidiarrheals.
  • Lab Test Considerations: May cause thrombocytopenia, leukopenia, and/or anemia. Monitor CBC at baseline and weekly during therapy. Absolute neutrophil count (ANC) should be ≥1.0 x 109/L and platelet count ≥50 x 109/L prior to each cycle and prior to resuming therapy following toxicity. Discontinue in patients who have recurrent ANC nadirs <0.5 c 109/L and/or recurrent platelet count nadirs <25 x 109/L after 2 dose reductions.
    • If platelet count ≥25 x 109/L and nadir ANC ≥0.5 x 109/L, continue therapy. If nadir ANC <0.5 x 109/L with any platelet count or platelet count <25 x 109/L with any nadir ANC, decrease dose by 25% to 750 mg/m2.
    • Other toxicities must be NCI-CTCAE Grade 2 or less prior to therapy. Any Grade 3 or 4 adverse reaction, decrease dose by 25%; if toxicity is nausea, vomiting, and diarrhea only decrease dose if duration is >7 days with supportive care.
    • May cause hepatotoxicity. Monitor liver function tests before therapy and at start of each cycle. Interrupt or adjust dose until recovery or permanently discontinue if severe.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)
Diarrhea (Adverse Reactions)

Implementation

  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers (see ).
  • Intravenous Administration
  • Intermittent Infusion: Reconstitute each vial of belinostat by adding 9 mL Sterile Water for injection into vial for a concentration of 50 mg/mL. Swirl until no particles are visible. Reconstituted solution may be stored at room temperature for up to 12 hr. Diluent: Withdraw volume needed and inject into 250 mL of 0.9% NaCl. Diluted solution may be kept at room temperature for up to 36 hr. Do not use solutions that are cloudy or contain a precipitate. Infuse through a 0.22 micron in-line filter.
  • Rate: Infuse over 30 min. If infusion site pain or other infusion-related symptoms occur, extend infusion to 45 min.

Patient/Family Teaching

  • Instruct patient to read the Patient Information sheet prior to starting therapy and with each cycle in case of changes.
  • Advise patient to notify health care professional if signs and symptoms of low platelet counts (unusual bleeding and bruising), low red blood cell count (weakness, tiredness, pale skin, dyspnea), infection (fever, flu-like symptoms, cough, shortness of breath, burning with urination, muscle aches, worsening skin problems), or liver problems (yellowing of skin and whites of eyes, dark urine, itching, pain in upper right stomach area).
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
  • Advise patient that this medication may have teratogenic effects. Contraception should be used during therapy. Advise female patient to avoid breastfeeding.
  • Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

  • Decreased spread of relapsed/refractory of peripheral T-cell lymphoma.
References in periodicals archive ?
The nine new antineoplastic agents and their indications are belinostat (Beleodaq) for peripheral T-cell lymphoma; blinatumomab (Blincyto) for acute lymphoblastic leukemia; ceritinib (Zykadia) for non-small cell lung cancer; idelalisib (Zydelig) for some types of leukemia and lymphoma; nivolumab (Opdivo) for metastatic melanoma; olaparib (Lynparza) for ovarian cancer; pembrolizumab (Keytruda) for unresectable or metastatic melanoma; ramucirumab (Cyramza) for gastric or gastroesophageal adenocarcinoma and metastatic non-small cell lung cancer; and siltuximab (Sylvant) for multicentric Castleman disease.
The move, which will combine Topotarget's flagship Belinostat drug and BioAlliance Pharma's Livatag and Validive drugs, is seen to establish a leading orphan oncology player, backed by a complementary portfolio of late-stage products addressing unmet medical needs, the parties have said.
The plan is aimed at securing the company's financing capabilities until it receives expected significant milestone payments related to the development of Belinostat for the treatment of peripheral T-Cell lymphoma (PTCL).
The reorganisation means that Topotarget will reduce its expenses and concentrate on the future development of cancer drug candidate Belinostat.
With $115 million of cash and investments and a projected operating cash burn of approximately $25 million, we believe that we are in an excellent position to advance our core products, belinostat and CR011-vcMMAE, toward registration development during 2008 and to fund operations into 2011," commented Timothy Shannon, MD, President and Chief Executive Officer of CuraGen.
Safety profile suggests belinostat is acceptable for patients with Relapsed/Refractory Peripheral T-Cell Lymphoma (R/R PTCL), including difficult-to-treat patients with low platelet counts due to marrow involvement with their disease or poor marrow reserve.
Anders Vadsholt, Topotarget s CEO, also released a statement: The positioning of BioAlliance Pharma, their late stage assets and expertise makes BioAlliance Pharma a perfect fit as a company to merge with, allowing the acceleration of belinostat development in several new orphan oncology indications by leveraging on both team s synergistic expertise.
The decision to transfer the TNFSFs rights to Multimeric is explained by the fact that TopoTarget wishes to keep its focus on its leading compound the HDACi belinostat.
26 September 2011 - Danish biotech company Topotarget A/S (CPH:TOPO) said today it and its US partner Spectrum Pharmaceuticals Inc (NASDAQ:SPPI) have received full enrolment for the registrational pivotal trial with belinostat, for the treatment of peripheral T-Cell lymphoma (PTCL).
Belinostat, HDAC inhibitor for the treatment of cancer:
Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in hematology and oncology, today announced surpassing the primary endpoint in the pivotal, registrational Phase 2 BELIEF trial of belinostat, a pan-histone deacetylase (HDAC) inhibitor.
He will be in charge of leading and managing the company's cross-functional brand efforts for FUSILEV and ZEVALIN, as well as brand planning for apaziquone and belinostat.