Skip to Main Content

 

Damaj G et al. J Clin Oncol 2012;31:104–110

 

Premedication for bendamustine HCl: Premedications are not necessary for primary prophylaxis of infusion-related reactions. In the event of a non-severe infusion-related reaction, consider adding a histamine receptor (H1)-subtype antagonist (eg, diphenhydramine 25–50 mg intravenously or orally), an antipyretic (eg, acetaminophen 650–1000 mg orally), and a corticosteroid (eg, methylprednisolone 100 mg intravenously) administered 30 minutes prior to bendamustine HCl administration in subsequent cycles

 

Bendamustine HCl 120 mg/m2 per dose; administer intravenously in a volume of 0.9% sodium chloride injection (0.9% NS) sufficient to produce a concentration with the range 0.2–0.6 mg/mL over 30–60 minutes, on 2 consecutive days, days 1 and 2, every 21 days for 6 cycles (total dosage/21-day cycle = 240 mg/m2)

Notes on bendamustine HCl:

  • Bendamustine HCl can cause severe infusion-related reactions

    • For grade 1–2 infusion-related reactions, consider rechallenge with the addition of antihistamine, antipyretic, and corticosteroid premedications (as described in the above premedication section)

    • For grade 3 infusion-related reactions, consider permanent discontinuation versus rechallenge with the addition of antihistamine, antipyretic, and corticosteroid premedications (as described in the above premedication section) after weighing risks and benefits

    • For grade 4 infusion-related reactions, permanently discontinue bendamustine HCl

  • Coadministration of strong CYP1A2 inhibitors (eg, ciprofloxacin, fluvoxamine) may increase exposure to bendamustine HCl and decrease exposure to its active metabolites. Concomitant CYP1A2 inducers (eg, omeprazole, cigarette smoking) may decrease exposure to bendamustine HCl and increase exposure to its active metabolites. Use caution, or select an alternative therapy, when coadministration of bendamustine HCl with strong CYP1A2 inhibitors or inducers is unavoidable

  • Bendamustine HCl formulations may vary by country; consult local regulatory-approved labeling for guidance. For example, in the United States, the Food and Drug Administration–approved Bendeka® under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act on 7 December 2015. The Bendeka® product labeling contains specific dilution and administration instructions, thus:

    • Bendamustine HCl (Bendeka®, where available) 120 mg/m2 per dose; administer intravenously in a volume of 0.9% NS or 5% dextrose injection (D5W) sufficient to produce a concentration with the range 1.85–5.6 mg/mL, over 10 minutes, on 2 consecutive days, days 1 and 2, every 21 days for 6 cycles (total dosage/21-day cycle = 240 mg/m2)

 

Supportive Care

Antiemetic prophylaxis

Emetogenic potential is MODERATE

See Chapter 39 for antiemetic recommendations

 

Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis MAY be indicated

See Chapter 43 for more information

 

Antimicrobial prophylaxis

Risk of fever and neutropenia is INTERMEDIATE

  Antimicrobial primary prophylaxis to be considered:

  • Antibacterial—consider a fluoroquinolone during periods of prolonged neutropenia, or no prophylaxis

  • Antifungal—consider use during periods of prolonged neutropenia

  • Antiviral—antiherpes antivirals (eg, acyclovir, famciclovir, valacyclovir)

See Chapter 47 for more information

Patient Population Studied

The prospective, open-label, single-agent, phase 2 trial involved 60 patients with relapsed/refractory, histologically confirmed, stage IIB or higher, peripheral T-cell lymphoma or cutaneous T-cell lymphoma. Eligible patients were aged ≥18 years, and had an Eastern Cooperative Oncology Group (ECOG) performance status score ≤3, measurable disease (≥2 cm in the longest diameter on cross-sectional computed tomography and measurable in 2 perpendicular dimensions), and received 1–3 prior lines of chemotherapy. Patients with Sézary syndrome, T-cell leukemia-lymphoma associated with human T-lymphotrophic virus, or prior history of malignancies other than T-cell lymphoma within the preceding 3 years were ineligible. Patients received up to six 21-day cycles of intravenous bendamustine (120 mg/m2 over 30–60 minutes on days 1 and 2)

Efficacy (N = 60)

Favorite Table | Download (.pdf) | Print
Efficacy (N = 60)
Overall response rate after three cycles 50%
Median duration of response 3.50 months
Median progression-free survival 3.63 months
Median overall survival 6.27 months
Overall response rate includes patients with either a complete or partial response to treatment

Therapy Monitoring

  1. Prior to treatment initiation: CBC with differential, chemistries (potassium, uric acid, phosphorus, calcium, serum creatinine, LDH), serum bilirubin, ALT or AST, urine pregnancy test (women of child-bearing potential only)

  2. Prior to each cycle: CBC with differential, serum chemistries, serum bilirubin, ALT or AST

  3. Weekly during treatment: CBC with differential

  4. In patients at high risk for tumor lysis syndrome (eg, high tumor burden, renal dysfunction, rapidly progressing disease, markedly elevated LDH, baseline abnormalities in laboratory indices of tumor lysis syndrome [potassium, phosphate, uric acid, calcium, serum creatinine]): Consider frequent monitoring of laboratory indices of tumor lysis syndrome, intravenous hydration, and prophylaxis with a xanthine oxidase inhibitor (eg, allopurinol) during the first cycle

  5. Monitor periodically for: Signs and symptoms of infection and dermatologic toxicity

  6. Response assessment every 2–3 cycles: Physical examination, CT scans

Treatment Modifications

Favorite Table | Download (.pdf) | Print
Treatment Modifications
Bendamustine Dose Modifications
Starting dose 120 mg/m2 per dose on days 1 and 2
Dose level 1 90 mg/m2 per dose on days 1 and 2
Dose level 2 60 mg/m2 per dose on days 1 and 2
Dose level 3 Discontinue bendamustine
Hematologic Toxicity
Day 1 platelet count <75,000/mm3 or Day 1 ANC <1000/mm3 Delay start of cycle until platelet count ≥ 75,000/mm3 and ANC ≥1000/mm3 or until recovery to near baseline values, then reduce by 1 dose level for subsequent cycles. Consider G-CSF use in subsequent cycles for dose-limiting neutropenia
G4 neutropenia (ANC <500/mm3) or G4 thrombocytopenia (platelet count <25,000/mm3) Delay start of cycle until platelet count ≥75,000/mm3 and ANC ≥1000/mm3 or until recovery to near baseline values, then reduce the bendamustine dosage by 1 dose level for subsequent cycles. Consider G-CSF use in subsequent cycles for dose-limiting neutropenia or severe neutropenic complications
Infectious Complications
Active infection Interrupt bendamustine until resolution of infection, then resume bendamustine at either the same dose, or reduced by 1 dose level, depending on the severity of infection
Drug Interactions
Patient requires concomitant therapy with a CYP1A2 inhibitor (eg, fluvoxamine, ciprofloxacin) Consider alternative treatment instead of the CYP1A2 inhibitor. If the CYP1A2 inhibitor cannot be avoided, use caution, and monitor carefully for bendamustine adverse effects
Patient requires concomitant therapy with a CYP1A2 inducer (eg, omeprazole), or patient is a smoker Consider alternative treatment instead of the CYP1A2 inducer. Recommend cessation of smoking, if applicable. If the CYP1A2 inducer cannot be avoided, use caution and monitor carefully for reduced bendamustine efficacy
Other Toxicities
≥G3 nonhematologic toxicity during the prior cycle Delay start of cycle until nonhematologic toxicity resolves to ≤G1 or baseline, then reduce the bendamustine dosage by 1 dose level for subsequent cycles
Bendamustine hydrochloride may cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during therapy

Abbreviations: ANC, absolute neutrophil count; G-CSF, granulocyte colony-stimulating factor

 

References:

  1. Bendeka (bendamustine hydrochloride injection) prescribing information. North Wales, PA: Teva Pharmaceuticals USA, Inc; 2018 July

  2. Damaj G et al. J Clin Oncol 2012;31:104–110

Adverse Events (N = 60)

The most frequent grade 3–4 adverse events were neutropenia (which occurred in 57% patients) and thrombocytopenia (occurring in 38% patients). The other most frequent grade 3–4 toxicities included infections, skin reactions, mucositis, and arrhythmia. Serious adverse events not related to disease progression occurred in 31 (52%) patients. Deaths secondary to infections occurred in four (7%) patients

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.

>