title: The combined use of radiation therapy and lonidamine in the treatment of brain metastases.
abstract: Lonidamine is an indazole carboxylic acid that has been shown to be synergistic with radiotherapy (RT) in tissue culture and animal models. Clinical experience has shown that lonidamine is well-tolerated, and appears to potentiate the activity of conventional chemotherapy in the treatment of brain metastases. A prospective randomized trial was undertaken to evaluate the use of lonidamine in combination with RT in the treatment of brain metastases. All patients received 3000 cGy of whole brain radiotherapy (WBRT). Fifty eight patients were enrolled; 31 received lonidamine plus WBRT and 27 received WBRT alone. There was no significant difference in response rate or survival between the treatment groups. Lonidamine blood levels were measured in 30 of the 31 patients who received the drug, and were therapeutic (greater than or equal to 15 micrograms/ml) in 50%. Survival and response rate were unaffected by the presence or absence of a therapeutic lonidamine level. The most common side-effects of lonidamine were myalgia, testicular pain, anorexia, and ototoxicity; however, only 2 patients had to discontinue the drug because of intolerable myalgias. No serious organ toxicity or myelosuppression was observed.
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: L M
authors.initials: LM
authors.lastname: DeAngelis
authors.forename: V E
authors.initials: VE
authors.lastname: Currie
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: G
authors.initials: G
authors.lastname: Krol
authors.forename: M A
authors.initials: MA
authors.lastname: O'Hehir
authors.forename: F M
authors.initials: FM
authors.lastname: Farag
authors.forename: C W
authors.initials: CW
authors.lastname: Young
authors.forename: J B
authors.initials: JB
authors.lastname: Posner
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007191:Indazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011720:Pyrazoles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D011720:Pyrazoles; C016371:lonidamine