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Return to: Twitter Facebook Linkedin Reddit Get Citation Citation Disclaimer: These citations have been automatically generated based on the information we have and it may not be 100% accurate. Please consult the latest official manual style if you have any questions regarding the format accuracy. AMA Citation Therapy H. Therapy H Therapy, Hematology-Oncology. Brain Cancer: Glioblastoma Regimen: Lomustine and Bevacizumab. Hematology-Oncology Therapy Updates, 29 November 2018. McGraw-Hill, 2018. AccessHemOnc. https://hemonc.mhmedical.com/updatesContent.aspx?gbosid=452893§ionid=204842622APA Citation Therapy H. Therapy H Therapy, Hematology-Oncology. (2018). Brain cancer: glioblastoma regimen: lomustine and bevacizumab. Boyiadzis MM. Boyiadzis M.M. Boyiadzis, Michael M. Hematology-oncology therapy updates. McGraw-Hill. https://hemonc.mhmedical.com/updatesContent.aspx?gbosid=452893§ionid=204842622.MLA Citation Therapy H. Therapy H Therapy, Hematology-Oncology. "Brain Cancer: Glioblastoma Regimen: Lomustine and Bevacizumab." Hematology-Oncology Therapy Updates Boyiadzis MM. Boyiadzis M.M. Boyiadzis, Michael M. McGraw-Hill, 2018, https://hemonc.mhmedical.com/updatesContent.aspx?gbosid=452893§ionid=204842622. Download citation file: RIS (Zotero) EndNote BibTex Medlars ProCite RefWorks Reference Manager Mendeley © Copyright Tools Clip Full Chapter Figures Only Tables Only Videos Only Supplementary Content Top Brain Cancer: Glioblastoma Regimen: Lomustine and Bevacizumab by Hematology-Oncology Therapy Listen + +Update to Chapter 5: Brain Cancer + Taal W et al. Lancet Oncol 2014;15:943–953 Wick W et al. N Engl J Med 2017;377:1954–1963 Protocol for: Wick W et al. N Engl J Med 2017;377:1954–1963 (https://www.nejm.org/doi/suppl/10.1056/NEJMoa1707358/suppl_file/nejmoa1707358_protocol.pdf) Bevacizumab 10 mg/kg; administer intravenously in 100 mL 0.9% sodium chloride injection (0.9% NS) on days 1, 15, and 29, every 6 weeks until disease progression (total dosage/6-week cycle = 30 mg/kg), plus: Note: Bevacizumab administration duration for the initial dose is 90 minutes. If administration is well tolerated, the administration duration may be decreased stepwise during subsequent administrations to 60 minutes and, finally, to a minimum duration of 30 minutes Lomustine 90 mg/m2 (maximum dose = 160 mg); administer orally as a single dose, without food, on day 1, every 6 weeks, until disease progression (total dosage/6-week cycle = 90 mg/m2; maximum dosage/6-week cycle = 160 mg) Notes: In the absence of ≥grade 2 hematologic toxicity, may increase the lomustine dose to 110 mg/m2 starting with cycle 2, thus: Lomustine 110 mg/m2 (maximum dose = 200 mg); administer orally as a single dose, without food, on day 1, every 6 weeks, until disease progression (total dosage/6-week cycle = 110 mg/m2; maximum dosage/6-week cycle = 200 mg) To reduce the likelihood of a medication error leading to severe myelosuppression, prescribe, dispense, and administer only enough capsules to supply 1 dose of lomustine. Educate patients that only 1 dose of lomustine is to be taken every 6 weeks and only after documentation of adequate hematologic recovery. (ISMP 2014; https://www.ismp.org/resources/oral-chemotherapy-we-simply-must-do-better. Accessed June 20, 2018) Supportive Care Antiemetic prophylaxis Emetogenic potential on day 1 is MODERATE–HIGH Emetogenic potential on days 15 and 29 is MINIMAL See Chapter 39 for antiemetic recommendations Hematopoietic growth factor (CSF) prophylaxis Primary prophylaxis is NOT indicated See Chapter 43 for more information Antimicrobial prophylaxis Risk of fever and neutropenia is LOW Antimicrobial primary prophylaxis to be considered: Antibacterial—not indicated Antifungal—not indicated Antiviral—not indicated unless patient previously had an episode of HSV See Chapter 47 for more information +Patient Population Studied + A multicenter, randomized, phase 3 trial (European Organisation for Research and Treatment of Cancer [EORTC] 26101) involved 437 patients with progressive glioblastoma after standard chemoradiation. Patients were randomly assigned in a 2:1 ratio to lomustine plus bevacizumab or lomustine alone. Patients in the combination therapy group received lomustine (90 mg/m2 with maximal dose of 160 mg, but increased to 110 mg/m2 with maximal dose of 200 mg if no grade >1 hematologic toxic effects were noted in the first cycle) every 6 weeks plus bevacizumab (10 mg/kg) every 2 weeks. Patients in the monotherapy group received lomustine (110 mg/m2; maximal dose of 200 mg) every 6 weeks. +Efficacy (N = 437) + Table Graphic Jump LocationFavorite Table | Download (.pdf) | Print Efficacy (N = 437) Lomustine plus Bevacizumab (N = 288) Lomustine Alone (N = 149) Median overall survival 9.1 months 8.6 months HR 0.95, 95% CI 0.74–1.21; P = 0.65 Median progression-free survival 4.2 months 1.5 months HR 0.49, 95% CI 0.39–0.61; P <0.001 Objective response rate 41.5% 13.9% +Therapy Monitoring + Prior to each dose of lomustine: CBC with differential, platelet count, LFTs, BUN, creatinine, electrolytes Baseline pulmonary function studies with frequent PFTs during treatment Prior to each dose of bevacizumab: Vital signs, urine dipstick for protein (perform 24-hour urine collection if ≥2+ protein) Weekly: CBC with differential, platelet count (monitor blood counts weekly for 6 weeks after a dose). Thrombocytopenia occurs at about 4 weeks postadministration and persists for 1–2 weeks. Leukopenia occurs at 5–6 weeks after a dose and persists for 1–2 weeks Response assessment: Contrast-enhanced MRI of the brain every 6 weeks for 6 months, then every 12 weeks thereafter +Treatment Modification + Table Graphic Jump LocationFavorite Table | Download (.pdf) | Print Treatment Modification BEVACIZUMAB DOSE MODIFICATIONS Adverse Event Treatment Modification Gastrointestinal perforations (gastrointestinal perforations, fistula formation in the gastrointestinal tract, intra-abdominal abscess), fistula formation involving an internal organ Discontinue bevacizumab permanently Serious bleeding Wound dehiscence requiring medical intervention Nephrotic syndrome Hypertensive crisis or hypertensive encephalopathy or reversible posterior leukoencephalopathy syndrome (RPLS) Congestive heart failure Necrotizing fasciitis Severe arterial or venous thromboembolic events Discontinue bevacizumab permanently; the safety of reinitiating bevacizumab after a thromboembolic event is resolved is not known Moderate to severe proteinuria Patients with a ≥2+ urine dipstick reading should undergo further assessment, eg, a 24-hour urine collection. Suspend bevacizumab administration for ≥2 g of proteinuria/24 h and resume when proteinuria is <2 g/24 h Severe hypertension not controlled with medical management Hold bevacizumab pending further evaluation and treatment of hypertension Mild, clinically insignificant infusion reaction Decrease the rate of infusion Clinically significant but not severe infusion reaction Interrupt the infusion in patients with clinically significant infusion reactions and consider resuming at a slower rate following resolution. If decision is made to restart, the infusion may be continued at ≤50% of the rate prior to the reaction and increased in 50% increments every 30 minutes if well tolerated. Infusions may be restarted at the full rate during the next cycle Severe infusion reaction—hypertension, hypertensive crises associated with neurologic signs and symptoms, wheezing, oxygen desaturation, G3 hypersensitivity, chest pain, headaches, rigors, and diaphoresis) Stop infusion and administer appropriate medical therapy (eg, epinephrine, corticosteroids, intravenous antihistamines, bronchodilators and/or oxygen). Discontinue bevacizumab Planned elective surgery Suspended bevacizumab at least 28 days before elective surgery and do not resume for at least 28 days after surgery or until surgical incision is fully healed Recent hemoptysis Do not administer bevacizumab Evidence of rectosigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction LOMUSTINE DOSE MODIFICATIONS Lomustine dose levels Dose level +1 110 mg/m2 as a single dose; maximum 200 mg Starting dose 90 mg/m2 as a single dose; maximum 160 mg Dose level -1 75 mg/m2 as a single dose; maximum 130 mg No >G1 neutropenia and no >G1 thrombocytopenia during cycle 1 Increase lomustine to dose level +1 beginning with cycle 2 Day 1 WBC <4000/mm3 or platelets <100,000/mm3 Delay therapy until WBC ≥4000/mm3 and platelets ≥100,000/mm3 WBC nadir during the prior cycle <2000/mm3, or ANC nadir during the prior cycle <1000/mm3, or platelet nadir during the prior cycle <50,000/mm3 Delay therapy until WBC ≥4000/mm3 and platelets ≥100,000/mm3 if necessary, then reduce lomustine to dose level -1 in subsequent cycle(s) ≥G3 liver toxicity (AST/ALT >5× ULN) and/or ≥G2 bilirubin (>1.5–3× ULN) Delay therapy until resolution to ≤G1 (AST/ALT ≤3× ULN; bilirubin ≤1.5× ULN), then reduce lomustine 1 dose level in subsequent cycle(s) Any G4 nonhematologic toxicity Discontinue lomustine ≥G2 nonhematologic toxicity that does not recover to ≤G1 within 2 weeks Any ≥G2 nonhematologic toxicity that recurs at the next cycle to ≥G2 Any pulmonary symptoms, but with PFT showing DLco ≥ predicted value Continue with same lomustine dose Any pulmonary symptoms, but with PFT showing <60% of predicted value Discontinue lomustine Decreased oxygen saturation at rest (eg, pulse oximeter <88% or Pao2 ≤55 mm Hg) Shortness of breath at rest or shortness of breath that limits self-care or ADL Severe cough limiting self-care or ADL Cumulative lomustine dosage >1100 mg/m2 Discontinue lomustine due to concerns of developing pulmonary fibrosis Creatinine clearance 10–50 mL/min Reduce lomustine dose by 25% Creatinine clearance <10 mL/min Reduce lomustine dose by 50–75% Notes: • Usually no more than a total of 6–7 cycles (660–770 mg/m2) of lomustine is recommended. Patients receiving >1100 mg/m2 cumulative lomustine dosage have a higher risk of developing pulmonary toxicity. Patients with a baseline FVC or DLco <70% are particularly at risk (GLEOSTINE™ [lomustine] capsules; June 2018 product label. NextSource Biotechnology, LLC, Miami, FL) • Patients who are pregnant or who become pregnant should be apprised of the potential hazard to the fetus from therapy with lomustine +Adverse Events (N = 430) + Grade 3–5✫ adverse events were recorded in 63.6% of patients assigned to lomustine plus bevacizumab and in 38.1% of patients assigned to lomustine alone. Grade 3–5 adverse events of special interest were pulmonary embolism (in 5% of the combination therapy group), arterial hypertension (in 24% of the combination therapy group and in <1% of the monotherapy group), and hematologic toxic effects (in 54% of the combination therapy group and in 50% of the monotherapy group). Deaths unrelated to the tumor were noted for 5 (2%) patients assigned to combination therapy (2 from myocardial infarctions, 1 from large-intestine perforation, 1 from sepsis, and 1 from intracranial hemorrhage) and 1 patient (<1%) assigned to monotherapy (as a result of lung infection). Treatment-related adverse events occurred in 85.2% and 53.1% of patients assigned to combination therapy and monotherapy, respectively, and treatment-related serious adverse events occurred in 38.5% and 9.5% of patients, respectively. ✫According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.