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A Combination Therapy of Dexamethasone and Somatostatin Analog Reintroduces Objective Clinical Responses to LHRH Analog in Androgen Ablation-Refractory Prostate Cancer Patients

Department of Experimental Physiology (M.K., C.M.), Medical School, University of Athens, Athens, 11527 Greece; Department of Urology (T.D.), Panagia Hospital, Foundation of Public Insurance, Thessaloniki, 55132 Greece; Institute of Brachytherapy and Urology (A.I., A.N.), Ygeia Health Center, Maroussi, Athens, 15123 Greece; Department of Urology (T.L.), Thriassion General Hospital, National System of Public Health, Athens, 19200 Greece

Address all correspondence and requests for reprints to: Michael Koutsilieris, M.D., Ph.D., Department of Experimental Physiology, Medical School, University of Athens, 75 Mikras Asias, Goudi 115 27, Athens, Greece. E-mail: mkouts{at}medscape.com

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 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.

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