title: Phase II trial of weekly Docetaxel, Zoledronic acid, and Celecoxib for castration-resistant prostate cancer.
abstract: Background Treatment options for patients with metastatic castration-resistance prostate cancer are unsatisfactory. Docetaxel monotherapy offers promising results with a tolerable toxicity profile. However, enhancing the clinical index of Docetaxel-based therapy remains the ultimate goal. Methods We conducted a phase II, open label, multinational prospective trial to evaluate the efficacy of weekly Docetaxel combined with Zoledronic acid and Celecoxib. Eligible patients received 25 mg/m(2) Docetaxel weekly for 3 consecutive weeks every 4 weeks, 4 mg Zoledronic acid every 4 weeks, and 200 mg oral Celecoxib twice daily. Enrollment was terminated prematurely upon the publication of reports of cardiac toxicity associated with cyclooxygenase (COX) 2 inhibitors. Results Our study enrolled 22 patients with a median of 4.7 cycles per patient. The median overall survival (OS) was 9.8 months (range 0.7 to 24.1 months) with 36 % and 4.5 % survival rates at 1 and 2 years, respectively. Our patients had a biologic response in 40.1 % of cases and a palliative response in 72.7 %. Among the eight patients with measurable disease, three had partial responses, two had stable disease, and three had progressive disease, leading to a response rate (RR) of 62.5 %. The observed toxicities were mild and limited to grade 3 events. Nine patients had anemia (40.1 %), 5 had sensory neuropathy (22.7 %) and 2 had stomatitis (9.1 %). Conclusion The combination of Docetaxel, Celecoxib, and Zoledronic acid failed to improve OS or to offer an acceptable biologic response. We do not believe that there is compelling evidence to include either Celecoxib or Zoledronic acid in further phase II/III trials.
authors.affiliation: Department of Oncology, Hotel-Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kattan
authors.affiliation: Nuclear Medicine Center, Bayrouni Center, Damascus, Syria.
authors.forename: Marwan
authors.initials: M
authors.lastname: Bachour
authors.affiliation: Department of Oncology, Hotel-Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
authors.forename: Fadi
authors.initials: F
authors.lastname: Farhat
authors.affiliation: Department of Oncology, Hotel-Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon. elie.rassy@hotmail.com.
authors.forename: Elie
authors.initials: E
authors.lastname: El Rassy
authors.affiliation: Department of Oncology, Hotel-Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
authors.forename: Tarek
authors.initials: T
authors.lastname: Assi
authors.affiliation: Department of Oncology, Hotel-Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
authors.forename: Marwan
authors.initials: M
authors.lastname: Ghosn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068579:Celecoxib / Q000009:adverse effects / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D052246:Cyclooxygenase 2 Inhibitors; D004164:Diphosphonates; D007093:Imidazoles; D043823:Taxoids; D000077143:Docetaxel; D000077211:Zoledronic Acid; D000068579:Celecoxib
keywords: Celecoxib; Docetaxel; Prostate cancer; Weekly chemotherapy; Zoledronic acid