Phase i study of tanespimycin in combination with bortezomib in patients with advanced solid malignancies

Erin Schenk, Andrea E Wahner Hendrickson, Donald W Northfelt, David O. Toft, Matthew M. Ames, Michael Menefee, Daniel Satele, Rui Qin, Charles Erlichman

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose To determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLT) of tanespimycin when given in combination with bortezomib. Experimental design Phase I dose-escalating trial using a standard cohort "3+3" design performed in patients with advanced solid tumors. Patients were given tanespimycin and bortezomib twice weekly for 2 weeks in a 3 week cycle (days 1, 4, 8, 11 every 21 days). Results Seventeen patients were enrolled in this study, fifteen were evaluable for toxicity, and nine patients were evaluable for tumor response. The MTD was 250 mg/m2 of tanespimycin and 1.0 mg/m2 of bortezomib when used in combination. DLTs of abdominal pain (13 %), complete atrioventricular block (7 %), fatigue (7 %), encephalopathy (7 %), anorexia (7 %), hyponatremia (7 %), hypoxia (7 %), and acidosis (7 %) were observed. There were no objective responses. One patient had stable disease. Conclusions The recommended phase II dose for twice weekly 17-AAG and PS341 are 250 mg/m2 and 1.0 mg/m2, respectively, on days 1, 4, 8 and 11 of a 21 day cycle.

Original languageEnglish (US)
Pages (from-to)1251-1256
Number of pages6
JournalInvestigational New Drugs
Volume31
Issue number5
DOIs
StatePublished - Oct 2013

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tanespimycin
Maximum Tolerated Dose
Neoplasms
Hyponatremia
Atrioventricular Block
Anorexia
Brain Diseases
Acidosis
Abdominal Pain
Fatigue
Research Design
Bortezomib

Keywords

  • Bortezomib
  • Phase I Trials
  • Solid tumors
  • Tanespimycin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

Phase i study of tanespimycin in combination with bortezomib in patients with advanced solid malignancies. / Schenk, Erin; Wahner Hendrickson, Andrea E; Northfelt, Donald W; Toft, David O.; Ames, Matthew M.; Menefee, Michael; Satele, Daniel; Qin, Rui; Erlichman, Charles.

In: Investigational New Drugs, Vol. 31, No. 5, 10.2013, p. 1251-1256.

Research output: Contribution to journalArticle

Schenk, Erin ; Wahner Hendrickson, Andrea E ; Northfelt, Donald W ; Toft, David O. ; Ames, Matthew M. ; Menefee, Michael ; Satele, Daniel ; Qin, Rui ; Erlichman, Charles. / Phase i study of tanespimycin in combination with bortezomib in patients with advanced solid malignancies. In: Investigational New Drugs. 2013 ; Vol. 31, No. 5. pp. 1251-1256.
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