Prolonged treatment with biologic agents for malignant glioma: a case study with high dose tamoxifen.

Traditional study design for treatment of malignant gliomas does not allow tumor progression to be greater than 25-50 percent without terminating treatment. This design may prevent recognition of patients who benefit from the treatment either by slowed growth or delayed response. A delayed response or slowed growth may be characteristic of biologic agents being evaluated in the treatment of malignant glioma. Because of the low toxicity of certain biologic drugs, continued treatment through tumor growth can be ethically considered in study design. The effect of biologic agents on a neoplasm may include cellular differentiation, retardation of growth, cytostasis, cytocidal effects, or apoptosis. Such effects may clinically translate into a complete response, partial response, stable disease or retardation of growth with or without an eventual reduction of tumor. We present a patient with a recurrent malignant glioma who was continued on high dose tamoxifen despite radiologic documented doubling of the tumor size and who eventually showed a delayed response to this agent nine months after initiation of treatment. Strong consideration should be given to the prolonged treatment of non-toxic biologic agents in a controlled clinical trial, where agents have shown some benefit in phase one studies.