title: An open-label, noncomparative phase II trial to evaluate the efficacy and safety of docetaxel in combination with gefitinib in patients with hormone-refractory metastatic prostate cancer.
abstract: BACKGROUND
  Prostate cancer is the most common type of cancer in men, however, therapeutic options are limited. 50-90% of hormone-refractory prostate cancer cells show an overexpression of epidermal growth factor receptor (EGFR), which may contribute to uncontrolled proliferation and resistance to chemotherapy. In vitro, gefitinib, an orally administered tyrosine kinase inhibitor, has shown a significant increase in antitumor activity when combined with chemotherapy.
  
  
  METHODS
  In this phase II study, the safety and efficacy of gefitinib in combination with docetaxel, a chemotherapeutic agent commonly used for prostate cancer, was investigated in patients with hormone-refractory prostate cancer (HRPC). 37 patients with HRPC were treated continuously with gefitinib 250 mg once daily and docetaxel 35 mg/m2 i.v. for up to 6 cycles. PSA response, defined as a =50% decrease in serum PSA compared with trial entry, was the primary efficacy parameter. PSA levels were measured at prescribed intervals.
  
  
  RESULTS
  The response rate and duration of response were consistent with those seen with docetaxel monotherapy. The combination of docetaxel and gefitinib was reasonably well tolerated in this study.
  
  
  CONCLUSIONS
  Future studies should investigate whether patients with specific tumor characteristics, e.g. EGFR protein overexpression, respond better to gefitinib than patients without, leading to a more customized therapy option.
authors.affiliation: University Hospital Basel, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Salzberg
authors.forename: Christoph
authors.initials: C
authors.lastname: Rochlitz
authors.forename: Rudolf
authors.initials: R
authors.lastname: Morant
authors.forename: George
authors.initials: G
authors.lastname: Thalmann
authors.forename: Augusto
authors.initials: A
authors.lastname: Pedrazzini
authors.forename: Enrico
authors.initials: E
authors.lastname: Roggero
authors.forename: Astrid
authors.initials: A
authors.lastname: Schönenberger
authors.forename: Alexander
authors.initials: A
authors.lastname: Knuth
authors.forename: Markus
authors.initials: M
authors.lastname: Borner
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D000077156:Gefitinib; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D000077156:Gefitinib