estramustine and lanreotide

The development of resistance to anticancer therapies is a major hurdle in preventing long-lasting clinical responses to conventional therapies in hormone-refractory prostate cancer. Herein, the molecular evidence documenting that bone metastasis microenvironment survival factors (mainly the paracrine growth hormone-independent, urokinase-type plasminogen activator-mediated increase of IGF-1 and the endocrine production of growth hormone-dependent IGF-1, mainly liver-derived IGF-1 production) produce an epigenetic form of prostate cancer cells that are resistant to proapoptotic therapies is reviewed. Consequently, the authors present the conceptual framework of a novel antibone microenvironment survival factor, mainly an anti-IGF-1 hormonal manipulation for androgen ablation refractory prostate cancer (a combination of conventional androgen ablation therapy [luteinising hormone-releasing hormone agonist-A or orchiectomy]) with dexamethasone plus somatostatin analogue, which yielded durable objective responses and major improvement of bone pain and performance status in stage D3 prostate cancer patients.

Topics: Adenocarcinoma; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Bone Neoplasms; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Dexamethasone; Drug Resistance, Neoplasm; Estramustine; Etoposide; Gonadotropin-Releasing Hormone; Growth Substances; Humans; Leuprolide; Male; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Orchiectomy; Osteoblasts; Osteoclasts; Paracrine Communication; Peptides, Cyclic; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Receptors, Androgen; Salvage Therapy; Somatostatin; Survival Analysis; Triptorelin Pamoate

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.. 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.. 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).. 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.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Dexamethasone; Diabetes Mellitus; Disease-Free Survival; Estramustine; Etoposide; Gastrointestinal Diseases; Gonadotropin-Releasing Hormone; Hematologic Diseases; Humans; Life Tables; Male; Middle Aged; Orchiectomy; Peptides, Cyclic; Prostatic Neoplasms; Somatostatin; Survival Analysis; Treatment Outcome; Triptorelin Pamoate

We report on a patient with androgen ablation-refractory prostate adenocarcinoma who had an objective response for longer than 24 months using a combination of estramustine and lanreotide. At baseline from our combination therapy, his prostate-specific antigen level was 21.30 ng/mL and serum chromogranin A level was 816 ng/mL. The patient discontinued complete androgen deprivation therapy and underwent combination therapy with oral estramustine 420 mg/day plus lanreotide acetate 73.9 mg intramuscularly every 4 weeks. After 33 months of follow-up, the patient was alive without clinical disease progression, and his prostate-specific antigen and chromogranin A level was 0.10 and 12 ng/mL, respectively.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chromogranin A; Chromogranins; Estramustine; Humans; Male; Peptides, Cyclic; Prostate-Specific Antigen; Prostatic Neoplasms; Somatostatin

Osteoblasts and osteoblast-derived survival growth factors, such as insulin-like growth factor I (IGF I), inhibit chemotherapy apoptosis of prostate cancer cells, thereby producing cytotoxic drug-resistant tumor growth, in vitro.. We tested a novel therapeutic approach, referred to as antisurvival factor (AFS) therapy, that aimed at reduction of osteoblast-derived IGFs, using dexamethasone (4 mg per os, qD) and growth hormone (GH)-dependent liver-derived IGFs, using a somatostatin-analog (lanreotide, 30 mg, intramuscularly (i.m.), q14D) in combination with triptorelin (3.75 mg, intramuscularly, q28D) to produce a clinical response in 4 patients with progressing hormone-refractory prostate cancer.. The patients given ASF therapy exhibited an excellent improvement of clinical performance and a decline of prostate-specific antigen (PSA) within 2 months of ASF therapy. One of them experienced excellent clinical response (normalization of PSA), two experienced good clinical response (decline of PSA of more than 50%), and one experienced stabilization (decline of PSA of less than 50%).. We conclude that this novel concept of combination therapy, using ASF with hormone ablation, is a promising salvage therapy that should be further assessed with a randomized clinical trial.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Dexamethasone; Doxorubicin; Estramustine; Humans; Male; Middle Aged; Peptides, Cyclic; Prostatic Neoplasms; Somatostatin; Triptorelin Pamoate