title: Phase I trial of weekly docetaxel, total androgen blockade, and image-guided intensity-modulated radiotherapy for localized high-risk prostate adenocarcinoma.
abstract: BACKGROUND
  This was a phase I study to find the maximum tolerable dose (MTD) of weekly docetaxel combined with high-dose intensity-modulated radiotherapy (IMRT) and androgen deprivation therapy (ADT).
  
  
  METHODS
  Men with localized high-risk prostate cancer (HRPC) were treated with weekly docetaxel at 10 to 30 mg/m(2) concurrent with IMRT of 77.4 Gy to the prostate and 45 Gy to the seminal vesicles. ADT consisted of a gonadotropin-releasing hormone agonist (GnRHa) and bicalutamide beginning 2 months before and during chemoradiation. GnRHa was continued for 24 months.
  
  
  RESULTS
  Nineteen patients were enrolled. No dose-limiting toxicity (DLT) was seen with docetaxel doses up to 25 mg/m(2). At the 30 mg/m(2) level, 2 of 4 patients experienced DLTs of both grade 3 fatigue and dyspepsia. At 41 months' median follow-up, 2 patients had died--1 from metastatic prostate cancer and the other from heart failure. Two other patients experienced biochemical failure. One patient with bladder invasion at diagnosis experienced late grade 2 urinary hesitancy 9 months after completion of radiotherapy, requiring short-term intermittent catheterization. All patients had erectile dysfunction, but no late toxicities worse than grade 2 were identified.
  
  
  CONCLUSIONS
  Weekly docetaxel may be combined with high-dose IMRT and long-term ADT up to a MTD of 25 mg/m(2). Acute toxicities and long-term side effects of this regimen were acceptable. Future studies evaluating the efficacy of docetaxel, ADT, and IMRT for localized HRPC should use a weekly dose of 25 mg/m(2) when limiting the irradiated volume to the prostate and seminal vesicles.
authors.affiliation: Medical University of South Carolina, Charleston, SC. Electronic address: marshadt@musc.edu.
authors.forename: David T
authors.initials: DT
authors.lastname: Marshall
authors.affiliation: Medical University of South Carolina, Charleston, SC.
authors.forename: Stephen
authors.initials: S
authors.lastname: Ramey
authors.affiliation: Medical University of South Carolina, Charleston, SC.
authors.forename: Ali-Reza
authors.initials: AR
authors.lastname: Golshayan
authors.affiliation: Medical University of South Carolina, Charleston, SC.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Keane
authors.affiliation: Medical University of South Carolina, Charleston, SC.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Kraft
authors.affiliation: University of California, San Francisco, Fresno, CA.
authors.forename: Uzair
authors.initials: U
authors.lastname: Chaudhary
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage; D000813:Anilides / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D000077143:Docetaxel; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000401:mortality / Q000628:therapy*; D061089:Radiotherapy, Image-Guided; D050397:Radiotherapy, Intensity-Modulated; D043823:Taxoids / Q000008:administration & dosage; D014105:Tosyl Compounds / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D043823:Taxoids; D014105:Tosyl Compounds; D000077143:Docetaxel; C053541:bicalutamide
keywords: Androgen deprivation therapy; Docetaxel; High-risk prostate cancer; Radiotherapy