Investigational New Drugs

, Volume 31, Issue 5, pp 1251–1256 | Cite as

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

  • Erin Schenk
  • Andrea E. Wahner Hendrickson
  • Donald Northfelt
  • David O. Toft
  • Matthew M. Ames
  • Michael Menefee
  • Daniel Satele
  • Rui Qin
  • Charles ErlichmanEmail author


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.


Phase I Trials Tanespimycin Bortezomib Solid tumors 


Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Erin Schenk
    • 1
  • Andrea E. Wahner Hendrickson
    • 1
  • Donald Northfelt
    • 1
  • David O. Toft
    • 2
  • Matthew M. Ames
    • 1
    • 4
  • Michael Menefee
    • 1
  • Daniel Satele
    • 3
  • Rui Qin
    • 3
  • Charles Erlichman
    • 1
    Email author
  1. 1.Division of Medical OncologyMayo Clinic College of MedicineRochesterUSA
  2. 2.Department of Biochemistry and Molecular BiologyMayo Clinic College of MedicineRochesterUSA
  3. 3.Division of BiostatisticsMayo Clinic College of MedicineRochesterUSA
  4. 4.Department of PharmacologyMayo Clinic College of MedicineRochesterUSA

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