title: 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.
authors: Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA.
authors: Andrea E Wahner
authors: AE
authors: Hendrickson
authors: Ann L
authors: AL
authors: Oberg
authors: Gretchen
authors: G
authors: Glaser
authors: John K
authors: JK
authors: Camoriano
authors: Prema P
authors: PP
authors: Peethambaram
authors: Gerardo
authors: G
authors: Colon-Otero
authors: Charles
authors: C
authors: Erlichman
authors: S Percy
authors: SP
authors: Ivy
authors: Scott H
authors: SH
authors: Kaufmann
authors: Larry M
authors: LM
authors: Karnitz
authors: Paul
authors: P
authors: Haluska
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016227:Benzoquinones / Q000008:administration & dosage / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D047029:Lactams, Macrocyclic / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D016227:Benzoquinones; D014408:Biomarkers, Tumor; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; D047029:Lactams, Macrocyclic; D003841:Deoxycytidine; C112765:tanespimycin; D000093542:Gemcitabine