Chemotherapy

The selection of a specific chemotherapeutic combination for use in patients with brain metastases from testicular GCTs is dependent on a number of factors. One factor is the presence of adequate renal, pulmonary, and hepatic function and other potential intercurrent illnesses. Another is prior drug exposure and the length of the time interval since that exposure (see further discussion in Chapters 13,14, and 16).

For patients with an initial presentation and with adequate renal and hepatic function, there are two regimens that have been reported on extensively in combination with whole-brain radiation therapy and/or surgery. The first regimen, favored in the

United States and many other parts of the world, is a combination of bleomycin, etoposide, and cisplatin (BEP), given every 3 weeks for four cycles.19,43 The second regimen, favored in the United Kingdom for selected poor-risk cases, is the POMB/ACE regimen (see Chapter 14)—cisplatin, vincristine (Oncovin), methotrexate, and bleomycin, alternating with actin-omycin D, cyclophosphamide, and etoposide.11,12,16,34 This regimen involves the use of more rapid cycling of agents on a treatment schedule that repeats every 2 weeks. The two regimens have never been compared to each other in a structured or randomized trial setting. Such comparisons are unlikely to happen, given the relatively low incidence of testicular cancer and cerebral metastasis, with even large centers seeing only a few cases per year. The BEP regimen has the advantage of being familiar to most medical oncologists and is associated with less unpredictable toxicity. However, it contains two drugs, cisplatin and bleomycin, that have variable penetration of the CNS. POMB/ACE is a more intense regimen with more toxicity than the BEP regimen in some hands, especially when administered infrequently at the treating center. It has the advantage of cycling a series of drugs that have better CNS penetration, in the form of moderate-dose methotrex-ate, actinomycin D, and etoposide. Reports from Charing Cross Hospital of using multimodal therapy incorporating POMB/ACE describe complete brain and systemic responses in 80% of patients, with intermediate- to long-term disease-free survival in most of these patients. Both BEP and POMB/ACE combinations require significant resources and skill to administer them safely with concurrent radiation and are optimally given in a center with significant experience in GCT management. Support with blood products and judicious assessment and treatment of infections and hemorrhagic problems is mandatory. Initial admission to an intensive care service for close monitoring is optimal. The availability of rapid access to ventilatory and inotropic support and neu-rosurgical intervention is also essential.

For patients presenting with chemorefractory disease, there is no defined optimal regimen. Many large centers maintain cisplatin in the regimen and add ifosfamide and etoposide or vinblastine, similar to standard salvage regimens such as the etoposide/

ifosfamide/cisplatin (VIP) or vinblastine/ifosfamide/ cisplatin (VelP) regimen (see Chapters 14 and 16) 21,46 Precautions similar to those discussed above need to be exercised in following these cases, despite the fact that the prognosis of these patients is worse. Among the newer drugs, the taxanes and gemcitabine have activity against the disease,17,55 but their place in therapy and in combination or salvage therapy for patients with brain metastases has not been determined. There is some experience in a few centers with combined high-dose chemotherapy and concurrent radiation therapy with stem cell res-cue.33 The initial results of this approach appear promising but must be placed in the context of the facts that high-dose chemotherapy protocols have not demonstrated a sustained survival advantage in refractory patients and that the role of such therapy in GCT management is yet to be determined.

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