Elsevier

Urology

Volume 63, Issue 1, January 2004, Pages 120-125
Urology

Adult urology
Combination of LHRH analog with somatostatin analog and dexamethasone versus chemotherapy in hormone-refractory prostate cancer: a randomized phase II study

https://doi.org/10.1016/j.urology.2003.08.041Get rights and content

Abstract

Objectives

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.

Section snippets

Patient population

During a 2-year period, 40 patients were recruited for this randomized Phase II study. Patients were eligible if they had Eastern Cooperative Oncology Group performance status of 0 to 3, had adenocarcinoma of the prostate that was progressing despite androgen deprivation, with measurable or assessable metastases, and had not received prior chemotherapy, diethylstilbestrol, estramustine, dexamethasone, or a somatostatin analog. All antiandrogen therapy was discontinued for at least 1 month, and

Results

The patient and disease characteristics are shown in Table I and were well balanced between the two treatment groups.

The PSA response data are shown in Table II. Approximately one half of the patients in each group achieved at least a 50% reduction in their PSA level. The median time for a PSA response was 7 weeks in the chemotherapy group and 9 weeks in the combination therapy group. An improved or stable bone scan was noted in 59% and 44%, respectively, of patients with osseous disease in

Comment

In our patients with HRPC, chemotherapy with estramustine and etoposide was compared with the combination of the somatostatin analog lanreotide and dexamethasone in addition to androgen ablation by orchiectomy or the LHRH analog triptorelin. The two treatments resulted in similar responses in terms of PSA level, measurable disease, osseous disease, time to progression, and overall survival. The quality of life, expressed as the performance status and pain score, did not differ between the two

Acknowledgements

To the following physicians for contributing patients to the study: Charalambos Arvanitis, Athanasios Bekos, Michael Bourounis, Antonios Farmakis, Charalambos Fasoulakis, Paraskevas Kalomiris, Ioannis Kastriotis, Petros Kirtsis, Theoharis Lambou, Michael Likourinas, Konstantinos Papoulis, Iraklis Poulias, Zoucher Sami, and Athanasios Tsintavis.

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