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

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Summary

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.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Medical Oncology, Mayo Clinic College of Medicine, Mayo Clinic, Gonda 19, 200 First Street, S.W, Rochester, MN, 55905, USA

    Erin Schenk, Andrea E. Wahner Hendrickson, Donald Northfelt, Matthew M. Ames, Michael Menefee & Charles Erlichman

  2. Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA

    David O. Toft

  3. Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, MN, USA

    Daniel Satele & Rui Qin

  4. Department of Pharmacology, Mayo Clinic College of Medicine, Rochester, MN, USA

    Matthew M. Ames

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  1. Erin Schenk
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  2. Andrea E. Wahner Hendrickson
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  9. Charles Erlichman
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Correspondence to Charles Erlichman.

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Schenk, E., Hendrickson, A.E.W., Northfelt, D. et al. Phase I study of tanespimycin in combination with bortezomib in patients with advanced solid malignancies. Invest New Drugs 31, 1251–1256 (2013). https://doi.org/10.1007/s10637-013-9946-7

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  • DOI: https://doi.org/10.1007/s10637-013-9946-7

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