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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
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Chemotherapy regimens for germ cell tumors: Bleomycin, etoposide, and cisplatin (BEP)[1]

Chemotherapy regimens for germ cell tumors: Bleomycin, etoposide, and cisplatin (BEP)[1]
Cycle length: 21 days.
Total cycles: 3 to 4.*
Drug Dose and route Administration Given on days
Bleomycin 30 unitsΔ IV per dose Dilute in 50 mL normal saline (NS) and administer over 10 minutes. Days 1, 8, and 15
Etoposide 100 mg/m2 IV per day Dilute in 500 mL NS (concentration less than 0.4 mg/mL) and administer over one hour. Days 1 through 5
Cisplatin 20 mg/m2 IV per day Dilute in 250 mL NS and administer over two hours. Do not administer with aluminum needles or intravenous sets. Days 1 through 5
Pretreatment considerations:
Hydration
  • Induction of diuresis using at least 2000 mL of NS minimizes the risk of cisplatin nephrotoxicity. Fluid administration should be adequate to establish a urine flow of at least 100 mL/hour for two hours prior to and two hours after cisplatin administration.
  • Refer to UpToDate topics on cisplatin nephrotoxicity.
Emesis risk
  • HIGH (>90% frequency of emesis).
  • Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults. 
Vesicant/irritant properties
  • Bleomycin, etoposide, and cisplatin are classified as irritants. Cisplatin can cause significant tissue damage; avoid extravasation.[2]
  • Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
Infection prophylaxis
  • Primary prophylaxis with granulocyte colony stimulating factors (G-CSF) is not indicated.
  • Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
Dose adjustment for baseline liver or kidney dysfunction
  • Bleomycin should not be administered in patients with a baseline creatinine >2.0 mg/dL. A lower initial dose of cisplatin or etoposide may be needed for patients with kidney or hepatic dysfunction.[2,3]
  • Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents; and chemotherapy nephrotoxicity and dose modification in patients with kidney impairment, conventional cytotoxic agents.
Monitoring parameters:
  • CBC with differential and platelet count weekly during treatment.
  • Basic metabolic panel (creatinine and electrolytes) prior to each treatment cycle.
  • Liver function tests prior to each treatment cycle.
  • Assessment of baseline pulmonary function tests (PFTs), including a diffusing capacity for carbon monoxide (DLCO), should be performed prior to bleomycin treatment and repeated at intervals during therapy.
Suggested dose modifications for toxicity:
Myelotoxicity
  • Each cycle should begin on schedule regardless of the degree of myelosuppression.[1] If febrile neutropenia or thrombocytopenic bleeding occurs, a dose reduction of 25% for etoposide should be used for subsequent cycles. If neutrophil count remains ≤2500 cells/microL or platelets remain ≤100,000/microL, G-CSF should be administered.
  • Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
Pulmonary toxicity
  • Bleomycin can be associated with the development of life-threatening pulmonary toxicity. Maximum lifetime bleomycin dose should not exceed 400 mg. Discontinue bleomycin in patients with clinical or radiographic evidence of pulmonary injury, or decline in the DLCO of 25% or more, even if asymptomatic. Do not reintroduce bleomycin to patients with any bleomycin-induced lung injury.
Neurologic toxicity
  • Neuropathy usually is seen after cumulative doses of cisplatin beyond 400 mg/m2, although there is marked interindividual variation. Patients with mild neuropathy can continue to receive full cisplatin doses. However, if the neuropathy interferes with function, the risk of potentially disabling neurotoxicity must be weighed against the benefit of continued treatment. Peripheral neuropathies can occur with prolonged courses (four to seven months) of cisplatin. Cisplatin treatment should be discontinued with the first signs and symptoms of the development of neurotoxicity.[2,5]
  • Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
Kidney toxicity
  • Treatment in the setting of kidney impairment (ie, creatinine >2.0 mg/dL or GFR <50 mL/min) requires a balanced discussion of the goals of treatment and the risks of cisplatin nephrotoxiciy in the face of impaired kidney function.
If there is a change in body weight of at least 10%, doses should be recalculated.
This table is provided as an example of how to administer this regimen; there may be other acceptable methods. This regimen must be administered by a clinician trained in the use of chemotherapy, who should use independent medical judgment in the context of individual circumstances to make adjustments, as necessary.

CBC: complete blood count; GFR: glomerular filtration rate; IV: intravenous.

* The precise number of cycles depends on the stage of the germ cell tumor.

¶ Cumulative lifetime dose of bleomycin should be limited to 400 units because of the increased rates of pulmonary toxicity. Refer to UpToDate topics on bleomycin-induced lung injury.

Δ 1 unit = 1 mg.

References:
  1. Nichols CR, Catalano PJ, Crawford ED, et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol 1998; 16:1287.
  2. Cisplatin injection, powder, lyophilized, for solution. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on December 8, 2011).
  3. Etoposide injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on December 9, 2011).
  4. Bleomycin sulfate injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on December 8, 2011).
  5. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2011; 29:4189.
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