The use of chemotherapy for PCNSL is expanding [26-41] (Table 16.7). Patients receiving chemotherapy and radiotherapy live longer than those receiving radiotherapy alone [36, 41-44]. The median survival following combinations of radiation and chemotherapy has ranged from 16 to 44.5 months; the 5-year survival rate is 20-30%. Long-term follow-up in one group of 31 patients revealed frequent relapse (15 of 29 patients) and a high rate of late neurologic toxicity, especially in patients older than 60 years . Patients with AIDS-associated disease, selected for good performance status, lack of active comorbid disease and high CD4 counts, may also benefit from chemotherapy .
Differences among chemotherapy regimens for primary CNS lymphoma are numerous: the agents used, the timing of administration (before or after radiotherapy) and the method of delivery (intravenous, intrathecal, or intra-arterial). The chemotherapeutic agents used are those with demonstrated efficacy against systemic lymphomas: corticosteroids, methotrex-ate, vinca alkaloids and alkylating agents. Corticosteroids lyse tumor cells and induce radiographic and clinical remission, but their effects are often brief. Methotrexate penetrates the intact blood brain barrier. It has demonstrated impressive efficacy against primary CNS lymphoma . Although agents such as cyclophosphamide have been used with success against systemic lymphomas, they have not proven as efficacious against CNS disease, probably because of poor penetration of the blood-brain barrier.
Toxicity depends on the drug used. In general, acute systemic effects include mucosi-tis, myelosuppression, nausea, vomiting and alopecia. Cognitive impairment is the feared late complication. Methotrexate administered after radiotherapy has been implicated in a higher incidence of this problem.
The rationale for administering chemotherapy before radiotherapy is twofold: (1) since radiotherapy often results in complete radiographic remission, administering it first prevents assessment of the effect of chemotherapy on measurable disease, and (2) the neurologic toxicity of some chemotherapeutic agents, including methotrexate, is less frequent and less severe when the drug is given prior to, rather than after, radiation. Intrathecal injection and intra-arterial delivery following blood-brain barrier disruption have been used to improve the penetration of these agents into the brain parenchyma .
Chemotherapy alone, with radiotherapy reserved for failure, has shown promise in uncontrolled trials [38-40]. The high initial response rates and the avoidance of radiation induced toxicity of this strategy warrant its further study.
TUMORS: CEREBRAL METASTASES AND LYMPHOMA
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