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A phase II study of gemcitabine in combination with tanespimycin in advanced epithelial ovarian and primary peritoneal carcinoma.

Abstract：

OBJECTIVE:To evaluate the efficacy and biological effects of the gemcitabine/tanespimycin combination in patients with advanced ovarian and peritoneal cancer. To assess the effect of tanespimycin on tumor cells, levels of the chaperone proteins HSP90 and HSP70 were examined in peripheral blood mononuclear cells (PBMC) and paired tumor biopsy lysates. METHODS:Two-cohort phase II clinical trial. Patients were grouped according to prior gemcitabine therapy. All participants received tanespimycin 154 mg/m(2) on days 1 and 9 of cycle 1 and days 2 and 9 of subsequent cycles. Patients also received gemcitabine 750 mg/m(2) on day 8 of the first treatment cycle and days 1 and 8 of subsequent cycles. RESULTS:The tanespimycin/gemcitabine combination induced a partial response in 1 gemcitabine naïve patient and no partial responses in gemcitabine resistant patients. Stable disease was seen in 6 patients (2 gemcitabine naïve and 4 gemcitabine resistant). The most common toxicities were hematologic (anemia and neutropenia) as well as nausea and vomiting. Immunoblotting demonstrated limited upregulation of HSP70 but little or no change in levels of most client proteins in PBMC and paired tumor samples. CONCLUSIONS:Although well tolerated, the tanespimycin/gemcitabine combination exhibited limited anticancer activity in patients with advanced epithelial ovarian and primary peritoneal carcinoma, perhaps because of failure to significantly downregulate the client proteins at clinically achievable exposures.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Hendrickson AE,Oberg AL,Glaser G,Camoriano JK,Peethambaram PP,Colon-Otero G,Erlichman C,Ivy SP,Kaufmann SH,Karnitz LM,Haluska P

doi

10.1016/j.ygyno.2011.10.002

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

210-5

issue

2

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(11)00814-6

journal_volume

124

pub_type

杂志文章

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