BEP (Bleomycin, Etoposide, Cisplatin) Chemotherapy Regimen for Testicular Cancer

Which Chemotherapy Medicines Are Included in the BEP Protocol?

• Bleomycin
• Etoposide
• cisPlatin

How Does BEP Work?

Each medicine in the BEP regimen is designed to stop cancer cells growing and kill them.

What Is the Aim of Treatment With the BEP Protocol?

BEP is usually given with curative intent (complete cure). Cure rates vary by disease stage. The complete cure rate can fall to 40% in high-risk patients and rise to 97% in early-stage (T2N0) disease.

- Related Topic: What Is Testicular Cancer? What Are Its Causes, Risk Factors, and Types?

BEP Administration, Dosage, and Schedule

• Bleomycin 30 units is administered slowly into a vein (I.V.=intravenous) over 10 minutes on treatment days 2, 9, and 16. Giving medicine intravenously over a specified time is called an infusion.
• Etoposide 100 mg/m2 is infused intravenously over 60 minutes on treatment days 1, 2, 3, 4, and 5.
• Cisplatin 20 mg/m2 is infused intravenously over 120 minutes on treatment days 1, 2, 3, 4, and 5.

Note: Medicine doses and administration times may vary according to your physician’s recommendations.

Estimated Duration of the BEP Regimen

• Administration may take up to 5 hours on days 1, 2, 3, 4, and 5, and approximately 1 hour on treatment days 2, 9, and 16. 
• Infusion times are based on clinical research but may vary depending on the doctor’s preference or the patient’s tolerance. Premedication and hydration may add time. 
• BEP is generally administered in outpatient chemotherapy units, with patients returning home afterward. 
• BEP is repeated every 21 days (3 weeks). This cycle is known as 1 course. Depending on the benefit obtained, treatment is generally given for 4 courses, although the physician may adjust this duration.

Side Effects of the BEP Regimen

In multidrug regimens, each medicine has its own side effects. The side effects that may arise when these two medicines are given together were estimated from clinical trial results. The most frequent side effects reported for BEP in clinical studies were: 

• Nausea (72%)
• Fatigue (63%) 
• Tingling, numbness, or burning in the fingers or toes (peripheral neuropathy) (36%)
• Mouth sores (35%) 
• Ringing in the ears (11%)
• Lung infection (11%) 
• Neutropenic fever (10%)
• Low white blood cell counts (8%)
• Kidney damage (4%)
• Increased bleeding risk [low platelets; thrombocytopenia]

Remember that these side-effect studies were conducted before many currently available anti-nausea medicines existed. Today, the percentage of patients experiencing nausea or vomiting is known to be much lower.

Follow-Up

How Frequently Do Patients Receiving BEP Chemotherapy Need Follow-Up?

Blood tests are recommended before each treatment. Required tests include a complete blood count, comprehensive metabolic panel (biochemistry), and blood magnesium and potassium levels. Other blood tests may be added at the physician’s discretion.

How Frequently Is Imaging (Radiological Examination) Needed?

Imaging may be checked before treatment, immediately after treatment finishes, and during routine follow-up. Imaging methods include computed tomography (CT), magnetic resonance imaging (MRI), PET scanning, bone scans, or X-rays.

Note: Lung function must be sufficiently healthy to receive bleomycin. Pulmonary function tests (PFTs) may generally be performed before treatment. Patients receiving bleomycin are monitored for pulmonary side effects during and after treatment.

How Do Blood Test or Imaging Results Affect Treatment?

Depending on the results, your doctor may continue BEP as planned, adjust its dose, or change treatment.

Points to Consider During and After BEP Treatment

• Intravenous (I.V.) fluids are given for hydration to protect against kidney damage while receiving cisplatin. These fluids may contain electrolytes such as potassium and magnesium. 
• Before the first bleomycin dose in the first course only, a small test dose may sometimes be given to help ensure infusion reactions do not occur. If tolerated, the remainder of the full dose is infused. The test dose does not need to be repeated every course.
• BEP may reduce sperm counts. Before starting treatment, discuss sperm banking with your physician to preserve the possibility of having children later. 
• Typically, after chemotherapy, white blood cell production is stimulated and periods of neutropenia are prevented by administering filgrastim (Neupogen, Tevagrastim, Leucostim, Fraven) or lenograstim (Granocyte). 
• Your oncology pharmacist should check for interactions between medicines.

Individual Medicine Label Information

Bleomycin (Blemisin, Bleocin-S, Bleolem)

Mechanism of Action

Although bleomycin’s precise mechanism is unknown, available evidence suggests its main action is inhibition of DNA synthesis and, to a lesser extent, RNA and protein synthesis. It is believed to chelate metal ions, principally iron, producing a pseudoenzyme that reacts with oxygen to generate superoxide and hydroxide free radicals that cleave DNA.

• Bleomycin is given as an intravenous (I.V.) infusion.
• The risk of severe lung infection increases in smokers, patients over 40, those with previous chest radiotherapy, those receiving supplemental oxygen, and those previously treated with bleomycin.
• It may cause wheezing or shortness of breath. To prevent this and establish that the remaining dose is safe, a test dose (1 unit) is given in the first course; the remaining dose may be administered if shortness of breath does not occur.
• Special dose adjustments may be needed in patients with kidney failure.

Common Bleomycin Side Effects

• It can cause skin changes such as rash or pigmentation. These may not develop until the second or third week of treatment.
• Mouth sores
• Hair loss
• Breathing problems

Etoposide (Etoposid Ebewe, Etoposide Amphar, Etoposide-Teva)

Mechanism of Action

Etoposide is derived from podophyllotoxin, a toxin found in the American mayapple plant. It was first synthesized in 1966 and approved in 1983 for cancer treatment by the United States Food and Drug Administration, the FDA . Etoposide targets DNA topoisomerase II enzyme activity, producing DNA breaks and triggering a response affecting several aspects of cellular metabolism.

• Etoposide is an intravenous (I.V.) infusion, generally given over 30-60 minutes or, in some circumstances, as a continuous infusion.
• Etoposide interacts with grapefruit juice, which may increase etoposide-related side effects when taken together.
• Special dose adjustments may be needed for reduced kidney or liver function.

Common Etoposide Side Effects

• Etoposide generally causes temporary hair loss. Hair grows back after treatment ends. 
• Digestive side effects such as diarrhea, mouth sores, and nausea may be common.
• Although uncommon, acute leukemia may develop (2-12%), typically 2-3 years after treatment.
• It may cause low blood counts (white blood cells, red blood cells, and platelets).

Cisplatin (Cisplatin Ebewe, Cisplatin-Koçak, Cisplatin DBL, Cisplatinum)

Mechanism of Action

Cisplatin’s effects on cancer cells are linked to its ability to cross-link purine bases in DNA. It interferes with DNA repair, causing DNA damage and subsequently triggering apoptosis, programmed cell death, in cancer cells. 

• Cisplatin is an intravenous (I.V.) infusion, typically given over one to two hours. 
• Long-term cisplatin use may cause severe infections in the kidneys. 
• Other side effects from multiple doses include low blood counts, nausea, vomiting, and hearing loss.
• Dose adjustments may be needed for reduced kidney function or reduced bone marrow function (low blood counts).
• Cisplatin is harmful to the human fetus; women should avoid pregnancy while taking this medicine.
• Women should not breastfeed while using cisplatin; it is known to pass into human milk. 

- Related Topic: The Revolutionary Cancer Medicine Cisplatin and Its Surprising Story

Common Cisplatin Side Effects

• Kidney problems may occur, especially in older patients.
• Nausea and vomiting may be acute (within the first 24 hours) or delayed (two to five days after infusion).
• Diarrhea 
• Low blood cell counts (myelotoxicity, acute leukemia) 
• Hearing problems and tinnitus. All patients should have a baseline hearing test.
• Low blood electrolytes: magnesium, potassium, calcium, sodium, and phosphate
• Numbness and tingling pain may occur in the hands and feet.
• Vision problems may occur; full recovery generally starts after therapy is stopped.
• Liver problems; recovery generally starts after therapy is stopped.

All Chemotherapy Regimens