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 a llow tumor progression to be greater than 25-50 percent without termin ating treatment. This design may prevent recognition of patients who b enefit 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 thr ough tumor growth can be ethically considered in study design. The eff ect of biologic agents on a neoplasm may include cellular differentiat ion, retardation of growth, cytostasis, cytocidal effects, or apoptosi s. Such effects may clinically translate into a complete response, par tial 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 rad iologic documented doubling of the tumor size and who eventually showe d a delayed response to this agent nine months after initiation of tre atment. Strong consideration should be given to the prolonged treatmen t of non-toxic biologic agents in a controlled clinical trial, where a gents have shown some benefit in phase one studies.