Is CBOP/BEP an alternative to BEP for patients with poor prognosis metastatic germ cell tumours?

The management of metastatic germ cell tumours (GCTs) with platinum-based chemotherapy represents a major success story. However, patients with poor-prognosis1 non-seminomatous GCTs (NSGCTs) with high tumour markers, non-pulmonary visceral metastases, or a mediastinal primary site at presentation have a less certain outcome. This group achieved cure rates <50% in an international pooled analysis despite being treated with standard bleomycin, cisplatin and etoposide chemotherapy (BEP).2There have been no clear improvements in the efficacy of first-line chemotherapy since the introduction of BEP in the mid-1980s. Four cycles of BEP given every 3 weeks remain the internationally accepted, standard of care for intermediate-prognosis and poor-prognosis patients,3 and three cycles of BEP given every 3 weeks4 is the most commonly endorsed regimen for good-prognosis patients.5 Attempts to improve survival have included use of multiagent regimens (eg, cisplatin, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide, etoposide (POMB/ACE);6 bleomycin, vincristine, cisplatin/etoposide, ifosfamide, cisplatin, and bleomycin (BOP/VIP-B));7 newer drugs such as ifosfamide,8 paclitaxel and high-dose chemotherapy.9–11 None have proved superior to BEP for overall survival (OS) in randomised trials and all are more toxic.12 Although the chemotherapy sensitivity of GCTs is a strong rationale for testing high-dose chemotherapy, this approach has been hampered by greater toxicity and some early deaths.13 ,14 An alternative approach has been to shorten the interval between courses of chemotherapy rather than increase the doses,15 but even this has been limited by toxicity.In order to improve survival for patients with poor-prognosis disease there is a need to better understand which patients will respond well to BEP and which patients need more intensive treatment. A retrospective study with 653 patients proposed that a subgroup with poor-prognosis NSGCT and an improved outcome could be identified based on tumour …