NCCP Chemotherapy Regimen

Bleomycin, Etoposide and CISplatin (BEP) Therapy

INDICATIONS FOR USE:
Regimen Reimbursement
INDICATION ICD10 Code Status
Adjuvant treatment of high risk (vascular invasion C62 00300a Hospital
carcinoma) stage 1 nonseminoma germ cell tumour
Metastatic germ cell tumours of the testis C62 00300b Hospital
Advanced stage or metastatic germ cell tumours C56 00300c Hospital
(dysgerminoma) of the ovaries
Extra-gonadal germ cell tumours C56/C62 00300d Hospital

TREATMENT:
The starting dose of the drugs detailed below may be adjusted downward by the prescribing clinician, using their
independent medical judgement, to consider each patients individual clinical circumstances.

Treatment with etoposide and CISplatin is administered on days 1-5, and treatment with bleomycin is
administered on days 1, 8 and 15 of a 21 day cycle.
For good risk patients - 3 cycles are administered,
For intermediate to poor risk patients - 4 cycles are administered

Facilities to treat anaphylaxis MUST be present when the chemotherapy is administered.

Admin Day Drug Dose Route Diluent & Rate

Order
a
1 1, 8 and 15 Bleomycin 30,000 International Units IV Bolus
(30mg) or IMb
2 1-5 Etoposide 100mg/m2 IV infusion 1000ml 0.9% NaCl over 60 minutesc
3 1-5 CISplatin 20mg/m2 IV infusion 1000ml 0.9% NaCl over 1 hour
(Pre hydration therapy required) d
Bleomycin dosing may be referred to in international units (IU) or in mg. 1,000 international units = 1mg
aThe total cumulative dose of bleomycin should NOT exceed 400,000 international units (400mg).

The risk of pulmonary toxicity increases beyond a cumulative dose of 300,000 international units (300mg).
bFor IM injection dose is dissolved in up to 5ml 0.9% NaCl. If pain occurs at the site of injection a 1% solution of lignocaine may be used as a solvent (6)

cHypotension following rapid IV administration has been reported.

Longer infusion times may be required based on the patient’s tolerance

d Prehydration therapy required for CISplatin

See local hospital policy recommendations.

Suggested prehydration for CISplatin therapy:
1. Administer 10mmol magnesium sulphate (MgSO 4) ((+/-KCl 20mmol/L if indicated) in 1000 mL sodium chloride 0.9% over 60 minutes.
Administer CISplatin as described above

ELIGIBILITY:
 Indications as above
 ECOG status 0-3

Published: 08/04/2016
NCCP Regimen: BEP Therapy Version number: 5
Review: 28/11/2024
Tumour Group: Genitourinary/Gynaecology ISMO Contributor: Dr Maccon Keane
Page 1 of 5
NCCP Regimen Code: 00300
The information contained in this document is a statement of consensus of NCCP and ISMO or IHS professionals regarding their views of currently accepted
approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of
individual clinical circumstances to determine any patient's care or treatment. Use of these documents is the responsibility of the prescribing clinician and is
subject to HSE’s terms of use available at http://www.hse.ie/eng/Disclaimer
This information is valid only on the day of printing, for any updates please check www.hse.ie/NCCPchemoregimens
 NCCP Chemotherapy Regimen

EXCLUSIONS:
 Hypersensitivity to bleomycin, etoposide, CISplatin or any of the excipients.
 Bleomycin is contraindicated in patients with acute pulmonary infection or chest X rays
suggesting diffuse fibrotic changes or greatly reduced lung function
 CISplatin
o Pre existing neuropathies ≥ grade 2
o Creatinine clearance < 40 mL/min
o Significant hearing impairment/tinnitus
 Severe liver impairment (etoposide)

PRESCRIPTIVE AUTHORITY:
The treatment plan must be initiated by a Consultant Medical Oncologist.

TESTS:
Baseline tests:
 FBC, renal and liver profile, creatinine
 Pulmonary function tests (PFTs) and Chest X-ray prior to bleomycin
 Consider sperm banking for appropriate patients prior to initiation of therapy
 Consider Audiometry testing

Regular tests:
 FBC weekly during treatment
 Renal and liver profile, creatinine prior to each treatment cycle
 Chest X-ray prior to each cycle
 PFTs as clinically indicated

Disease monitoring:
Disease monitoring should be in line with the patient’s treatment plan and any other test/s as directed
by the supervising Consultant.

DOSE MODIFICATIONS:
 Any dose modification should be discussed with a Consultant

Published: 08/04/2016
NCCP Regimen: BEP Therapy Version number: 5
Review: 28/11/2024
Tumour Group: Genitourinary/Gynaecology ISMO Contributor: Dr Maccon Keane
Page 2 of 5
NCCP Regimen Code: 00300
The information contained in this document is a statement of consensus of NCCP and ISMO or IHS professionals regarding their views of currently accepted
approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of
individual clinical circumstances to determine any patient's care or treatment. Use of these documents is the responsibility of the prescribing clinician and is
subject to HSE’s terms of use available at http://www.hse.ie/eng/Disclaimer
This information is valid only on the day of printing, for any updates please check www.hse.ie/NCCPchemoregimens
 NCCP Chemotherapy Regimen

Haematological:
 Delay and dose reductions are not recommended as the efficacy of this treatment may be greatly
compromised
 All delays to treatment must be approved by prescribing consultant.
 Prophylactic use of G-CSF is not recommended.
 G-CSF is indicated in patients receiving their second or subsequent cycle of BEP who have had an episode of
neutropenic fever or who have not recovered their neutrophil count by Day 5.

Renal and Hepatic Impairment:

Table 2: Dose modification in renal and hepatic impairment
Drug Renal impairment Hepatic Impairment
Bleomycin CrCl Dose No dose recommendations available in SmPC, clinical
(ml/min) decision
>50 100%
10-50 75%
<10 50%
Etoposide CrCl Dose Bilirubin AST Dose
(ml/min) (micromol/L) (Units/L)
>50 100%
15-50 75% 26-51 or 60-180 50%
<15 50% >51 or >180 Clinical
Subsequent dosing should be based on decision
patient tolerance and clinical effect.
CISplatin CrCl Dose No dose reduction necessary
(ml/min)
≥ 60 100%
*45-59 75%
<45 Hold CISplatin or delay
with additional IV fluids
*Due to the curative intent of this chemotherapy regimen , in cases where CrCl falls between 45-59ml/min it may be appropriate to maintain
dose of CISplatin but with extra hydration, longer infusion time and daily Creatinine measurements at the discretion of the prescribing
consultant.

Bleomycin Induced Lung Toxicity:

 Bleomycin can be associated with the development of life-threatening pulmonary toxicity.
 Bleomycin should be discontinued in patients demonstrating clinical or radiographic evidence of
pulmonary injury or significant deterioration of pulmonary diffusion capacity.
 Do not reintroduce bleomycin to patients with any bleomycin-induced lung injury.

SUPPORTIVE CARE:

EMETOGENIC POTENTIAL:
Days 1-5 High
Days, 8 15 Minimal (Refer to local policy).

Published: 08/04/2016
NCCP Regimen: BEP Therapy Version number: 5
Review: 28/11/2024
Tumour Group: Genitourinary/Gynaecology ISMO Contributor: Dr Maccon Keane
Page 3 of 5
NCCP Regimen Code: 00300
The information contained in this document is a statement of consensus of NCCP and ISMO or IHS professionals regarding their views of currently accepted
approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of
individual clinical circumstances to determine any patient's care or treatment. Use of these documents is the responsibility of the prescribing clinician and is
subject to HSE’s terms of use available at http://www.hse.ie/eng/Disclaimer
This information is valid only on the day of printing, for any updates please check www.hse.ie/NCCPchemoregimens
 NCCP Chemotherapy Regimen

PREMEDICATIONS:
Hydration prior to CISplatin administration (Reference local policy or see recommendations above).

OTHER SUPPORTIVE CARE:

No specific recommendations

ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS

The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full
details.
 Pulmonary toxicity: Bleomycin: may cause severe and life threatening pulmonary toxicity. Pulmonary
toxicity of bleomycin is both dose-related and age-related. It may also occur when lower doses are
administered, especially in elderly patients, patients with reduced kidney function, pre-existing lung
disease, previous or concurrent radiotherapy to the chest and in patients who need administration of
oxygen. It is significantly enhanced by thoracic radiation and by hyperoxia used during surgical
anaesthesia.
 Hypersensitivity: Hypersensitivity reactions have been reported with etoposide and CISplatin. Monitor
infusion of etoposide for the first 15 minutes for signs of hypotension.
 Neutropenia: Fever or other evidence of infection must be assessed promptly and treated appropriately.
Avoid aminoglycoside antibiotics.
 Renal Toxicity: Nephrotoxicity is common with CISplatin. Strongly encourage oral hydration. If oral
hydration is not possible (e.g. excessive nausea), IV hydration is indicated. Avoid nephrotoxic drugs such
as aminoglycoside antibiotics where possible. Where treatment with nephrotoxic drugs must be used,
monitor renal function.
 Ototoxicity and sensory neural damage: These are associated with CISplatin therapy. They should be
assessed by history prior to each cycle.

DRUG INTERACTIONS:
 Bleomycin causes sensitization of lung tissue to oxygen. If oxygen is required the use of low concentration
(e.g. 25%) is recommended. Fluid replacement should be carefully monitored with emphasis on
administration of colloid rather than crystalloid to avoid interstitial pulmonary oedema.
 CISplatin may potentiate the nephrotoxic and ototoxic effects of loop diuretics and aminoglycosides so
concurrent use should be avoided.
 Concomitant CISplatin therapy is associated with reduced total body clearance of etoposide.
 CYP3A4 inducers may increase the clearance of etoposide.
 CYP3A4 and p-gp inhibitors may decrease the clearance of etoposide
 Current drug interaction databases should be consulted for more information

ATC CODE:
Bleomycin L01DC01
CISplatin L01XA01
Etoposide L01CB01

Published: 08/04/2016
NCCP Regimen: BEP Therapy Version number: 5
Review: 28/11/2024
Tumour Group: Genitourinary/Gynaecology ISMO Contributor: Dr Maccon Keane
Page 4 of 5
NCCP Regimen Code: 00300
The information contained in this document is a statement of consensus of NCCP and ISMO or IHS professionals regarding their views of currently accepted
approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of
individual clinical circumstances to determine any patient's care or treatment. Use of these documents is the responsibility of the prescribing clinician and is
subject to HSE’s terms of use available at http://www.hse.ie/eng/Disclaimer
This information is valid only on the day of printing, for any updates please check www.hse.ie/NCCPchemoregimens
 NCCP Chemotherapy Regimen

REFERENCES:
1. Einhorn LH, Williams SD, Loehrer PJ, et al. Evaluation of optimal duration of chemotherapy in favorable-
prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J Clin Oncol 1989;
7:387-91
2. Williams S, Birch R, Einhorn LH et al. Treatment of disseminated germ-cell tumors with CISplatin,
bleomycin, and either vinblastine or etoposide. N Engl J Med, 1987; 316: 1435-1440
3. de Wit R, Roberts JT, Wilkinson P, et al. Final analysis demonstrating the equivalence of 3 BEP vs 4 cycles
and the 5 day schedule vs 3 days per cycle in good prognosis germ cell cancer. An EORTC/MRC phase III
study. Proc Am Soc Clin Oncol 2000; 19a:326a (abstract 1281).
4. Nichols 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; Vol 16 (No.4):
1287-1293
5. Williams SD, Blessing JA, Hatch KD et al. Chemotherapy of advanced dysgerminoma: trials of the
Gynecologic Oncology Group. J Clin Oncol 1991; 9(11):1950-1955.
6. Bleomycin, etoposide, and CISplatin (BEP) chemotherapy for germ cell tumors. UptoDate. January 2016
7. Bleo-Kyowa Summary of Product Characteristics Accessed September 2017. Available at
https://www.medicines.org.uk/emc/product/4263/smpc
8. Cisplatin (Eloxatin®) Summary of Product Characteristics HPRA.Last updated: 11/03/2019. Accessed
August 2019 Available at:
https://www.hpra.ie/img/uploaded/swedocuments/Final%20approved%20SPC%20PA0822.199.001.pdf
9. Etoposide 20 mg/ml Concentrate for Solution for Infusion Summary of Product Characteristics. HPRA Last
updated: 29/07/2019 Accessed November 2019 Available at:
https://www.hpra.ie/img/uploaded/swedocuments/Licence_PA2059-036-001_29072019103821.pdf
10. Dosage Adjustment for Cytotoxics in Renal Impairment January 2009; North London Cancer Network.
Available at http://londoncancer.org/media/65600/renal-impairment-dosage-adjustment-for-
cytotoxics.pdf
11. Dosage Adjustment for Cytotoxics in Hepatic Impairment January 2009; North London Cancer Network.
Available at http://londoncancer.org/media/65594/hepatic-impairment-dosage-adjustment-for-
cytotoxics.pdf
12. NCCP Classification Document for Systemic Anti-Cancer Therapy (SACT) Induced Nausea and Vomiting. V1
2018. Available at:
https://www.hse.ie/eng/services/list/5/cancer/profinfo/chemoprotocols/nccp%20antiemetic%20classific
ation%20document%20v1%202018.pdf

Version Date Amendment Approved By

1 08/04/2016 Dr Maccon Keane
2 27/09/2017 Updated with new NCCP regimen Prof Maccon Keane
template
3 06/12/2017 Updated with revised CISplatin Prof Maccon Keane
hydration regimen recommendations
4 20/11/2019 Reviewed. Standardised treatment table Prof Maccon Keane
and renal dose modifications.
5 11/11/2020 Updated baseline tests Prof Maccon Keane

Comments and feedback welcome at [email protected].

Published: 08/04/2016
NCCP Regimen: BEP Therapy Version number: 5
Review: 28/11/2024
Tumour Group: Genitourinary/Gynaecology ISMO Contributor: Dr Maccon Keane
Page 5 of 5
NCCP Regimen Code: 00300
The information contained in this document is a statement of consensus of NCCP and ISMO or IHS professionals regarding their views of currently accepted
approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of
individual clinical circumstances to determine any patient's care or treatment. Use of these documents is the responsibility of the prescribing clinician and is
subject to HSE’s terms of use available at http://www.hse.ie/eng/Disclaimer
This information is valid only on the day of printing, for any updates please check www.hse.ie/NCCPchemoregimens