histone deacetylase inhibitors
Treatment of relapsed/refractory peripheral T-cell lymphoma (PTCL).
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.
Decreased spread of relapsed/refractory PCTL.
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)
- Concurrent use of strong inhibitors of UGT1A1;
- OB: Pregnancy (may cause fetal harm);
- Lactation: Lactation.
Use Cautiously in:
- Advanced stage disease/large tumor burden (↑ risk of tumor lysis syndrome)
- Patients with UGT1A1*28 polymorphism (initial dose ↓ required);
- Moderate/severe hepatic impairment or CCr <39 mL/min
- Rep: Women of reproductive potential and men with female partners of reproductive potential
- Pedi: Safety and effectiveness not established in children.
Adverse Reactions/Side Effects
CV: hypotension, peripheral edema, phlebitis
Derm: pruritus, rash
F and E: hypokalemia
GI: HEPATOTOXICITY, nausea, vomiting, abdominal pain, ↓ appetite, constipation, diarrhea
GU: ↓ fertility (males), ↑ serum creatinine
Hemat: ANEMIA, LEUKOPENIA, THROMBOCYTOPENIA
Local: infusion site pain
Neuro: fatigue, dizziness, headache
Misc: INFECTION, TUMOR LYSIS SYNDROME, chills, fever
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Concurrent use of strong inhibitors of UGT1A1 including atazanvir, gemfibrozil, and indinavir may ↑ levels and risk of serious toxicity; avoid concurrent use.
IV (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.
Lyophilized powder for injection: 500 mg/vial
- 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:
Verify negative pregnancy test before starting therapy.
- 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.
- Risk for infection (Adverse Reaction)
- Diarrhea (Adverse Reaction)
- Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers.
- Intermittent Infusion: Reconstitution: 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. Dilution: 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.
- 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.
- Rep: Advise females of reproductive potential to use effective contraception during and for 6 mos after last dose and to avoid breastfeeding during and for 2 wks after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 3 mos after last dose. May impair male fertility.
- Emphasize the need for periodic lab tests to monitor for side effects.
Decreased spread of relapsed/refractory of peripheral T-cell lymphoma.