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.