title: A combination therapy of dexamethasone and somatostatin analog reintroduces objective clinical responses to LHRH analog in androgen ablation-refractory prostate cancer patients.
abstract: We evaluated whether the combination of triptorelin, a LHRH analog (LHRH-A), with dexamethasone and lanreotide, a somatostatin analog, can produce objective clinical responses in metastatic androgen ablation-refractory prostate cancer (stage D3) patients who have relapsed, after combined androgen blockade (LHRH-A plus antiandrogen) and antiandrogen withdrawal. Eleven stage D3 patients with diffuse bony metastases, who had progressed despite initial responses (lasting <12 months) to combined androgen blockade therapy and subsequently failed antiandrogen withdrawal, received oral dexamethasone (4 mg daily for the first month, tapered down to 2 mg after the first month and 1 mg after the second month, and continued on 1 mg thereafter) and lanreotide (30 mg im every 14 d) in combination with triptorelin (3.75 mg im every 28 d). Serum prostate-specific antigen, alkaline phosphatase, performance status, and bone pain were assessed monthly during therapy. Fasting blood glucose was measured biweekly, and serum IGF-I, T, and dehydroepiandrosterone sulfate levels were assessed at baseline, at response to the combination therapy, and at relapse from it. Ten of 11 stage D3 patients [90.9% of patients; 95% confidence interval (CI), 58.7-99.8%] had durable objective clinical responses (including > or = 50% prostate-specific antigen decline in 8 patients, 72.7%; 95% CI, 39-94%). All patients reported significant and durable improvement of bone pain (for a median duration of 13 months; 95% CI, 12-14 months; range, 6-22 months) and performance status (median duration, 19 months; 95% CI, 13-25 months; range, 7-22 months) without major treatment-related side effects. The median progression-free survival was 7 months (95% CI, 4-10 months; range, 3-17 months), and the median overall survival was 18 months (95% CI, 16-20 months; range, 7-22 months). Five of six total deaths occurred secondary to disease progression. We observed a statistically significant (P = 0.018) reduction in serum IGF-I levels at response to the combination therapy (60% reduction of baseline IGF-I levels). Dehydroepiandrosterone sulfate levels, although already significantly suppressed at baseline, had an additional significant reduction (P < 0.02) at response to therapy. T levels remained suppressed within castration levels (<3 nmol/liter, at baseline and throughout therapy, including relapse). The combination therapy of LHRH-A with dexamethasone plus somatostatin analog produces objective clinical responses and symptomatic improvement in androgen ablation (LHRH-A) refractory prostate cancer patients.
authors.affiliation: Department of Experimental Physiology, Medical School, University of Athens, Athens, 11527 Greece. mkouts@medscape.com
authors.forename: M
authors.initials: M
authors.lastname: Koutsilieris
authors.forename: C
authors.initials: C
authors.lastname: Mitsiades
authors.forename: T
authors.initials: T
authors.lastname: Dimopoulos
authors.forename: A
authors.initials: A
authors.lastname: Ioannidis
authors.forename: A
authors.initials: A
authors.lastname: Ntounis
authors.forename: T
authors.initials: T
authors.lastname: Lambou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D006728:Hormones / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D006728:Hormones; D010456:Peptides, Cyclic; C060347:lanreotide; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone