title: Pilot study of estramustine added to radiosurgery and radiotherapy for treatment of high grade glioma.
abstract: Patients with high grade glioma generally have poor prognoses. Addition of radiosensitizing agents might improve the response to irradiation. The chemotherapeutic agent estramustine sensitizes experimental gliomas to radiation. Gliomas express estramustine binding proteins, and cytotoxic concentrations of estramustine metabolites are found in gliomas after oral administration. Twenty three patients, aged 25-78, with new or recurrent high grade glioma were treated with estramustine and radiosurgery and/or radiotherapy. Patients with recurrent tumors were treated with estramustine and Gamma Knife stereotactic radiosurgery; eligible tumors were limited to 4 cm maximal diameter. Patients with newly diagnosed tumors were treated with estramustine and fractionated radiotherapy, with radiosurgery also performed if the tumor was less than 4 cm maximal diameter. Estramustine (16 mg/kg per day orally) was started three days prior to radiosurgery, or, if only radiotherapy was performed, on the first day of radiotherapy. Estramustine was continued until the completion of radiosurgery and/or radiotherapy (72 Gy, 60 fractions, 1.2 Gy bid over 6 weeks). Of the 13 patients treated for newly diagnosed glioblastoma, median survival was 16 months with 38% 2-year survival. Of five patients treated for recurrent glioblastoma, survival was 3, 8, 9, 15, and 23 + months. Two patients with recurrent anaplastic astrocytoma survived for 24 and 48+ months. One patient with recurrent anaplastic mixed glioma survived 5+ months. Two patients with newly diagnosed anaplastic oligodendroglioma survived 20 and 42+ months. Four of the new glioblastoma patients developed deep vein thrombosis. The results of this pilot study indicate some benefit, and further investigation incorporating estramustine into clinical trials is suggested.
authors.affiliation: Department of Neurological Surgery, University of Miami School of Medicine, Miami 33136, USA. hlandy@med.miami.edu
authors.forename: Howard
authors.initials: H
authors.lastname: Landy
authors.forename: Arnold
authors.initials: A
authors.lastname: Markoe
authors.forename: Priscilla
authors.initials: P
authors.lastname: Potter
authors.forename: Garrett
authors.initials: G
authors.lastname: Lasalle
authors.forename: Angela
authors.initials: A
authors.lastname: Marini
authors.forename: Niramol
authors.initials: N
authors.lastname: Savaraj
authors.forename: Isildinha
authors.initials: I
authors.lastname: Reis
authors.forename: Deborah
authors.initials: D
authors.lastname: Heros
authors.forename: Medhi
authors.initials: M
authors.lastname: Wangpaichitr
authors.forename: Lynn
authors.initials: L
authors.lastname: Feun
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004961:Estramustine / Q000627:therapeutic use*; D005260:Female; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D016634:Radiosurgery; D011878:Radiotherapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D011838:Radiation-Sensitizing Agents; D004961:Estramustine