A phase I study of the heat shock protein 90 inhibitor alvespimycin (17-DMAG) given intravenously to patients with advanced solid tumors.

Article Details

Citation

Pacey S, Wilson RH, Walton M, Eatock MM, Hardcastle A, Zetterlund A, Arkenau HT, Moreno-Farre J, Banerji U, Roels B, Peachey H, Aherne W, de Bono JS, Raynaud F, Workman P, Judson I

A phase I study of the heat shock protein 90 inhibitor alvespimycin (17-DMAG) given intravenously to patients with advanced solid tumors.

Clin Cancer Res. 2011 Mar 15;17(6):1561-70. doi: 10.1158/1078-0432.CCR-10-1927. Epub 2011 Jan 28.

PubMed ID
21278242 [ View in PubMed
]
Abstract

PURPOSE: A phase I study to define toxicity and recommend a phase II dose of the HSP90 inhibitor alvespimycin (17-DMAG; 17-dimethylaminoethylamino-17-demethoxygeldanamycin). Secondary endpoints included evaluation of pharmacokinetic profile, tumor response, and definition of a biologically effective dose (BED). PATIENTS AND METHODS: Patients with advanced solid cancers were treated with weekly, intravenous (i.v.) 17-DMAG. An accelerated titration dose escalation design was used. The maximum tolerated dose (MTD) was the highest dose at which /= 20 mg/m(2)) and sustained for 96 hours (>/= 40 mg/m(2)). Plasma HSP72 levels were greatest in the two patients who experienced DLT. At 80 mg/m(2) client protein (CDK4, LCK) depletion was detected and tumor samples from 3 of 5 patients confirmed HSP90 inhibition. Clinical activity included complete response (castration refractory prostate cancer, CRPC 124 weeks), partial response (melanoma, 159 weeks), and stable disease (chondrosarcoma, CRPC, and renal cancer for 28, 59, and 76 weeks, respectively). CONCLUSIONS: The recommended phase II dose of 17-DMAG is 80 mg/m(2) weekly i.v.

DrugBank Data that Cites this Article

Drugs