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Published on: January 19, 2019
Phase I study of tanespimycin in combination with bortezomib in patients with advanced solid malignancies
Erin Schenk1, Andrea E Wahner Hendrickson, Donald Northfelt
1Division of Medical Oncology, Mayo Clinic College of Medicine, Mayo Clinic, Gonda 19, 200 First Street, S.W, Rochester, MN, 55905, USA.
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/m(2) of tanespimycin and 1.0 mg/m(2) 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/m(2) and 1.0 mg/m(2), respectively, on days 1, 4, 8 and 11 of a 21 day cycle.
