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

Andrea E Wahner Hendrickson, Ann L Oberg, Gretchen Glaser, John K Camoriano, Prema P. Peethambaram, Gerardo Colon-Otero, Charles Erlichman, S. Percy Ivy, Scott H Kaufmann, Larry M Karnitz, Paul Haluska

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)210-215
Number of pages6
JournalGynecologic Oncology
Volume124
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

tanespimycin
gemcitabine
Carcinoma
Blood Cells
Neoplasms
Phase II Clinical Trials
Proteins
Neutropenia
Immunoblotting
Ovarian Neoplasms

Keywords

  • Gemcitabine
  • Heat shock protein 90
  • Ovarian cancer
  • Peritoneal cancer
  • Phase I/II trials
  • Tanespimycin

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

A phase II study of gemcitabine in combination with tanespimycin in advanced epithelial ovarian and primary peritoneal carcinoma. / Wahner Hendrickson, Andrea E; Oberg, Ann L; Glaser, Gretchen; Camoriano, John K; Peethambaram, Prema P.; Colon-Otero, Gerardo; Erlichman, Charles; Ivy, S. Percy; Kaufmann, Scott H; Karnitz, Larry M; Haluska, Paul.

In: Gynecologic Oncology, Vol. 124, No. 2, 02.2012, p. 210-215.

Research output: Contribution to journalArticle

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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 na{\"i}ve patient and no partial responses in gemcitabine resistant patients. Stable disease was seen in 6 patients (2 gemcitabine na{\"i}ve 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.",
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AU - Camoriano, John K

AU - Peethambaram, Prema P.

AU - Colon-Otero, Gerardo

AU - Erlichman, Charles

AU - Ivy, S. Percy

AU - Kaufmann, Scott H

AU - Karnitz, Larry M

AU - Haluska, Paul

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