Bleomycin, Etoposide and Cisplatinum (BEP) Chemotherapy for Metastatic Germ Cell Tumours: Treatment Outcomes at UKM Medical Centre, Malaysia

  • Azrif, Muhammad (Department of Radiotherapy & Oncology, UKM Medical Centre) ;
  • Leong, Yu Kong (Department of Radiotherapy & Oncology, UKM Medical Centre) ;
  • Aslan, Nik Muhammad (Department of Radiotherapy & Oncology, UKM Medical Centre) ;
  • Fong, Kua Voon (Department of Radiotherapy & Oncology, UKM Medical Centre) ;
  • Ismail, Fuad (Department of Radiotherapy & Oncology, UKM Medical Centre)
  • Published : 2012.06.30


Introduction: Although bleomycin/etoposide/cisplatinum (BEP) chemotherapy is established as the standard treatment for germ cell tumours, it requires significant experience in administration and toxicity management to maintain optimal dose intensity. A retrospective review of 30 patients was conducted at UKMMC to study treatment outcomes. Methods & Materials: Patients with GCTs and treated with at least two cycles of BEP chemotherapy between January 2003 and Oct 2009 were eligible for this study. Patients received 4-6 cycles of bleomycin 30,000IU IV D1, D8 & D15 and either etoposide $100mg/m^2$ IV D1-D5 and cisplatin $20mg/m^2$ IV D1-D5 (5 day BEP regimen) or etoposide $165mg/m^2$ D1-D3 and cisplatin $50mg/m^2$ D1-3 (3 day BEP regimen) every three weeks per cycle. All patients received prophylactic granulocyte colony-stimulating factor (GCSF) from days 6 to 10 of each cycle. The overall response rates, 2 year progression-free survival and overall survival of the whole cohort were assessed. Results: Thirty patients fulfilled the inclusion criteria. Non-seminomatous GCTs comprised 93.3% of cases and gonadal and mediastinal primary sites were the most common. Sixty percent were classified as IGCCCG poor risk disease. Median follow-up was 26.6 months. The overall response rate (CR+PR) was 70%. The two year PFS and OS were 70% and 66%. There was a significant difference in terms of the overall response rate (85% vs 40%, p = 0.03) and in PFS (94.7% vs 50%, p = 0.003) between gonadal and extragonadal primary sites. Conclusion: It is possible to achieve outcomes similar to those in international clinical trials with close monitoring and good supportive care of patients undergoing BEP chemotherapy. There is a strong argument for patients with IGCCCG poor prognosis disease to be treated in specialist tertiary centres to optimize treatment outcomes.


Germ cell tumour;BEP chemotherapy;prognosis;Malaysia


  1. Aass N, Klepp O, Cavallin Stahl E, et al (1991). Prognostic factors in unselected patients with non-seminomatous metastatic testicular cancer: a multicentre experience. J Clin Oncol, 9, 818-26.
  2. Bajorin DF, Nichols CR, Margolin KA, et al (2006). Phase 3 trial of conventional dose chemotherapy alone or with high dose chemotherapy for metastatic germ cell tumour patients: a cooperative group trial by memorial sloan kettering cancer center, ECOG, SWOG and CALGB. J Clin Oncol, 24, 219.
  3. Bokemeyer C, Kohrmann O, Tischer J, et al (1996). A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with good risk metastatic non-seminomatous germ cell tumors. Ann Oncol, 7, 1015-21.
  4. Collette L, Sylvester R, Stenning S, et al (1999). Impact of the treating institution on survival of patients with "poor prognosis" metastatic non-seminoma. J Natl Cancer Inst, 91, 839-46.
  5. Culine S, Kramar A, Theodore C, et al (2008). Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate and poor risk metastatic non-seminomatous germ cell tumours: genito-urinary group of the French federation of cancer centers trial T93MP. J Clin Oncol, 26, 421-7.
  6. De Wit R, Stoter G, Sleijfer DT, et al (1995). Four cycles of BEP versus an alternating regime of PVB and BEP in patients with poor prognosis metastatic testicular non-seminoma; a randomized study of the EORTC Genitourianry Tract Cancer Cooperative Group. British J Cancer, 71, 1311-4.
  7. De Wit R, Stoter G, Kaye SB, et al (1997). Importance of bleomycin in combination chemotherapy for good prognosis testicular non-seminoma: a randomized study of the European organization for research and treatment of cancer genitourinary tract cancer cooperative group. J Clin Oncol, 15, 1837-43.
  8. De Wit R, Roberts JT, Wilkinson PM, et al (2001). Equivalence of three or four cycles of bleomycin, etoposide and cisplatin chemotherapy and of 3- or 5- day schedule in good-prognosis germ cell cancer: a randomized study of the European organization for research and treatment of cancer trial and medical research council. J Clin Oncol, 19, 1629-40.
  9. Droz JP, Kramar A, Biron P, et al (2007). Failure of high-dose cyclophosphamide and etoposide combined with doubledose cisplatin and bone marrow support in patients with high volume metastatic non-seminomatous germ-cell tumours: mature results of a randomised trial. Eur Urol, 51, 739-48.
  10. Einhorn LH, Williams SD, Loehrer PJ, et al (1989). Evaluation of optimal duration of chemotherapy in favourable prognosis disseminated germ cell tumours: a southern cancer study group protocol. J Clin Oncol, 7, 387-91.
  11. Gerard L C C, Rampal S, Yahya H (2008). Cancer Incidence in PeninsularMalaysia 2003-2005. National Cancer Registry, the Ministry of Health, Malaysia.
  12. Harding MJ, Paul J, Gillis CR (1993). Management of malignant teratoma: does referral to a specialist unit matter? Lancet, 314, 999-1002.
  13. Horwich A, Sleijfer DT, Fossa D, et al (1997). Randomized trial of bleomycin, etoposide and cisplatin compared with a bleomycin, etoposide and carboplatin in good prognosis metastatic non-seminomatous germ cell cancer: a multi-institutional medical research Council/European organization for research and treatment of cancer trial. J Clin Oncol, 15, 1844-52.
  14. International Germ Cell Cancer Collaborative Group (1997). International germ cell consensus classification; a prognostic factor based staging system for metastatic germ cell cancers. J Clin Oncol, 15, 594-603
  15. Kaye SB, Mead GM, Fossa S, et al (1998). Intensive inductionsequential chemotherapy with BOP/VIP-B compared with treatment with BEP/EP for poor prognosis metastatic nonseminomatous germ cell tumour: a randomized medical research Council/ European organization for research and treatment of cancer study. J Clin Oncol, 16, 692-701
  16. Levi JA, Raghavan D, Harvey V, et al (1993). The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian germ cell trial group. J Clin Oncol, 11, 1300-5
  17. Loehrer Sr P, Johnson D, Elson P, Einhorn LH, Trump D (1995). Importance of bleomycin in favourable-prognosis disseminated germ cell tumours: an Eastern Co-operative Oncology Group trial. J Clin Oncol, 13, 470-6
  18. Nichols CR, Catalano PJ, Crawford ED, et al (1998). Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumours: an Eastern cooperative oncology group, Southwest oncology group and cancer and leukemia group B study. J Clin Oncol, 16, 1287-93