Journal Article

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

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

2013

Overview

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/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.

• Publisher: Springer US,Springer,Springer Nature B.V
• Subject: Aged / Aged, 80 and over / Analysis / Anticoagulants / Antineoplastic agents / Antineoplastic Agents - administration & dosage / Antineoplastic Agents - adverse effects / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Benzoquinones - administration & dosage / Benzoquinones - adverse effects / Biological and medical sciences / Boronic Acids - administration & dosage / Boronic Acids - adverse effects / Bortezomib / Cancer therapies / Disease / Dose-Response Relationship, Drug / Drug dosages / Drug therapy / Female / General aspects / Humans / Lactams, Macrocyclic - administration & dosage / Lactams, Macrocyclic - adverse effects / Male / Maximum Tolerated Dose / Medical schools / Medical sciences / Medicine / Medicine & Public Health / Middle Aged / Multiple myeloma / Neoplasms - drug therapy / Oncology / Pharmaceutical sciences / Pharmacology. Drug treatments / Pharmacology/Toxicology / Phase I Studies / Protein Kinase Inhibitors - administration & dosage / Protein Kinase Inhibitors - adverse effects / Proteins / Pyrazines - administration & dosage / Pyrazines - adverse effects / Radiation / Signal transduction / Studies / Toxicity / Treatment Outcome / Tumors