title: Combination of LHRH analog with somatostatin analog and dexamethasone versus chemotherapy in hormone-refractory prostate cancer: a randomized phase II study.
abstract: OBJECTIVE
  To evaluate prospectively the combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone in patients with hormone-refractory prostate cancer (HRPC) in a randomized Phase II study. HRPC presents a challenging therapeutic problem. Salvage chemotherapy is the usual approach at this stage of the disease. The combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone has produced objective clinical responses in HRPC.
  
  
  METHODS
  Forty patients with HRPC were randomized to receive one of two treatments. Group 1 underwent chemotherapy (estramustine 140 mg three times daily and etoposide 100 mg orally for 21 days) and group 2 the combination of a somatostatin analog (lanreotide 30 mg intramuscularly every 14 days) and dexamethasone (4 mg tapered to 1 mg), in addition to androgen ablation by orchiectomy or a luteinizing hormone-releasing hormone analog (triptorelin 3.75 mg intramuscularly every 28 days). The clinical and prostate-specific antigen (PSA) response, overall survival, time to progression, and toxicity were compared between the two groups.
  
  
  RESULTS
  The data of 20 patients in group 1 and 18 in group 2 were analyzed. The demographic and clinical data were similar in the two groups at study entry. A PSA response (decrease of greater than 50%) was observed in 45% of group 1 and 44% of group 2. The difference was not statistically significant. A partial clinical response was observed in 29% and 30% of groups 1 and 2, respectively. Again, the difference was not statistically significant. Changes in performance status and pain score during treatment were not significantly different in the two groups. Hematologic toxicity was more frequent in group 1 (80% of patients), and mild diabetes was more frequent in group 2 (22% of patients). The overall survival was 18.8 months in group 1 and 18 months in group 2 (not statistically significant). The time to progression was 6 versus 4 months and, in the PSA responder subgroup, it was 8 versus 7.7 months in groups 1 and 2, respectively (neither difference was statistically significant).
  
  
  CONCLUSIONS
  The results of our randomized Phase II study indicated that the new combination treatment (luteinizing hormone-releasing hormone analog, somatostatin analog, and dexamethasone) may be equally effective as salvage chemotherapy in patients with HRPC in terms of the clinical and PSA response, overall survival, and time to progression. A larger prospective Phase III trial is required to confirm our observations.
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Christos
authors.initials: C
authors.lastname: Kiamouris
authors.forename: Dimitra
authors.initials: D
authors.lastname: Gika
authors.forename: Charalambos
authors.initials: C
authors.lastname: Deliveliotis
authors.forename: Aris
authors.initials: A
authors.lastname: Giannopoulos
authors.forename: Anastasios
authors.initials: A
authors.lastname: Zervas
authors.forename: Christos
authors.initials: C
authors.lastname: Alamanis
authors.forename: Constantinos
authors.initials: C
authors.lastname: Constantinidis
authors.forename: Michael
authors.initials: M
authors.lastname: Koutsilieris
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D003920:Diabetes Mellitus / Q000139:chemically induced; D018572:Disease-Free Survival; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016019:Survival Analysis; D016896:Treatment Outcome; D017329:Triptorelin Pamoate / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D018931:Antineoplastic Agents, Hormonal; D010456:Peptides, Cyclic; D017329:Triptorelin Pamoate; C060347:lanreotide; D007987:Gonadotropin-Releasing Hormone; D004961:Estramustine; D013004:Somatostatin; D005047:Etoposide; D003907:Dexamethasone