title: Phase I study of tanespimycin in combination with bortezomib in patients with advanced solid malignancies.
abstract: OBJECTIVE
  To determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLT) of tanespimycin when given in combination with bortezomib.
  
  
  METHODS
  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.
authors.affiliation: Division of Medical Oncology, Mayo Clinic College of Medicine, Mayo Clinic, Gonda 19, 200 First Street, S.W, Rochester, MN, 55905, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Schenk
authors.forename: Andrea E Wahner
authors.initials: AE
authors.lastname: Hendrickson
authors.forename: Donald
authors.initials: D
authors.lastname: Northfelt
authors.forename: David O
authors.initials: DO
authors.lastname: Toft
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Ames
authors.forename: Michael
authors.initials: M
authors.lastname: Menefee
authors.forename: Daniel
authors.initials: D
authors.lastname: Satele
authors.forename: Rui
authors.initials: R
authors.lastname: Qin
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016227:Benzoquinones / Q000008:administration & dosage / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D047029:Lactams, Macrocyclic / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D001897:Boronic Acids; D047029:Lactams, Macrocyclic; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; C112765:tanespimycin; D000069286:Bortezomib
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