title: Sunitinib plus androgen deprivation and radiation therapy for patients with localized high-risk prostate cancer: results from a multi-institutional phase 1 study.
abstract: OBJECTIVE
  To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer.
  
  
  METHODS
  Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib.
  
  
  RESULTS
  Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy.
  
  
  CONCLUSIONS
  The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. pcorn@mdanderson.org
authors.forename: Paul G
authors.initials: PG
authors.lastname: Corn
authors.forename: Danny Y
authors.initials: DY
authors.lastname: Song
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Heath
authors.forename: Jordan
authors.initials: J
authors.lastname: Maier
authors.forename: Raymond
authors.initials: R
authors.lastname: Meyn
authors.forename: Deborah
authors.initials: D
authors.lastname: Kuban
authors.forename: Thomas A
authors.initials: TA
authors.lastname: DePetrillo
authors.forename: Paul
authors.initials: P
authors.lastname: Mathew
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000813:Anilides / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000379:methods; D004347:Drug Interactions; D005240:Feasibility Studies; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D016729:Leuprolide / Q000627:therapeutic use; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects; D011467:Prostate / Q000528:radiation effects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods; D012669:Seminal Vesicles / Q000528:radiation effects; D000077210:Sunitinib; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D000970:Antineoplastic Agents; D007211:Indoles; D009570:Nitriles; D011758:Pyrroles; D014105:Tosyl Compounds; D017273:Goserelin; C053541:bicalutamide; D017430:Prostate-Specific Antigen; D016729:Leuprolide; D000077210:Sunitinib
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