title: A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone.
abstract: OBJECTIVE
  To find the maximum tolerated dose (MTD) of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors.
  
  
  METHODS
  This was a Phase I study using cohort dose escalation of OSI-461 dosed orally twice daily in combination with mitoxantrone 12 mg/m(2) given on Day 1 of each 21-day cycle.
  
  
  RESULTS
  OSI-461 dose was escalated to 1,000 mg po bid. One patient experienced a dose-limiting toxicity (DLT). Three patients discontinued the study due to adverse events (AE). Two patients (10%) had a partial response, and ten patients (50%) had stable disease as best response.
  
  
  CONCLUSIONS
  The combination of OSI-461 and mitoxantrone was well tolerated. Dose escalation was stopped because of toxicities in a concurrent Phase I trial. The response rate seen in patients with prostate cancer was comparable to response rates seen in trials of mitoxantrone and prednisone alone, and further studies of the combination of OSI-461 and mitoxantrone were not pursued.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, CRB1-1M59, Baltimore, MD 21231, USA.
authors.forename: Lee P
authors.initials: LP
authors.lastname: Resta
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.forename: Mario A
authors.initials: MA
authors.lastname: Eisenberger
authors.forename: Avery
authors.initials: A
authors.lastname: Spitz
authors.forename: Serina
authors.initials: S
authors.lastname: King
authors.forename: Jennifer
authors.initials: J
authors.lastname: Porter
authors.forename: Amy
authors.initials: A
authors.lastname: Franke
authors.forename: Ramesh
authors.initials: R
authors.lastname: Boinpally
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D009369:Neoplasms / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013467:Sulindac / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013736:Testicular Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
chemical_list: C439285:(5-fluoro-2-methyl-1-(4-pyridyl)methylene-3-(N-benzyl)-indene)-acetamide hydrochloride; D000970:Antineoplastic Agents; D013467:Sulindac; D008942:Mitoxantrone
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