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Correspondence Re: E. Corey et al., Zoledronic Acid Exhibits Inhibitory Effects on Osteoblastic and Osteolytic Metastases of Prostate Cancer. Clin. Cancer Res., 9: 295ndash;306, 2003.

Department of Oncology, Campus Bio-Medico University, 00155 Rome, Italy

Susanna Scarpa

Department of Experimental Medicine and Pathology, La Sapienza University, Rome, Italy

Alfonso Baldi

Department of Biochemistry, Section of Pathology, Second University of Naples, Naples, Italy

We read with particular interest the experimental study by Corey et al. (1) in the "Experimental Therapeutics, Preclinical Pharmacology" section of the January 2003 issue of Clinical Cancer Research. The authors clearly show that zoledronic acid, a new-generation and potent bisphosphonate, displays antiproliferative, apoptotic, and cytostatic effects on prostate cancer cells in vitro and in vivo. This work confirms previous published papers on the same topic. In particular, Lee et al. (2) demonstrated that pamidronate and, in particular, zoledronic acid achieve a significant reduction of prostate cancer cell growth in an in vivo model and suggested that the clinical utility of bisphosphonates in managing skeletal metastases might be attributable in part to a direct inhibition of the growth of prostate cancer cells in the bone microenvironment. Moreover, recently the Institut National de la Santé et de la Recherche Médicale (INSERM) Research group (3) has shown that zoledronic acid strongly inhibits angiogenesis both in bone and in prostate tissues in a murine model. Furthermore, Saad et al. (4) clearly demonstrated that zoledronic acid reduces skeletal-related events in prostate cancer patients with bone metastases. Our research group performed a perspective study¹ to investigate the modifications of serum cytokines after a single zoledronic acid infusion (4 mg) in cancer patients with bone metastases. In all of the patients treated for the first time with zoledronic acid, we selected five patients with metastatic prostate cancer who had not receive radiotherapy, chemotherapy, immunotherapy, steroids, or hormonotherapy during the last 4 weeks before study accrual (the last administration of long-lasting release hormonotherapy was at least 3 months before). In these patients, we performed a PSA² assessment just before the beginning of drug infusion, and again at 7 and 21 days after the zoledronic acid infusion. In all of the five patients, we recorded a reduction of circulating PSA levels at both 7 and 21 days. In particular, we observed a reduction of 22 and 53% in median circulating PSA levels, respectively, 7 days and 21 days after zoledronic acid infusion. These results demonstrate for the first time in the literature, a reduction of a surrogate parameter of response that is clearly caused by bisphosphonate administration. Despite the low number of evaluated patients and the surrogate parameter of response used, these data may suggest a potential anticancer role for zoledronic acid in prostate cancer patients and could represent the basis for future prospective clinical trials aimed at investigating the antineoplastic role of bisphosphonates in prostate cancer.

FOOTNOTES

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Unpublished observations.

² The abbreviation used is: PSA, prostate-specific antigen.

³ To whom requests for reprints should be addressed, at Università Campus Bio-Medico, Via Emilio Longoni, 83, 00155 Rome, Italy. Phone: 39-06-22541738; Fax: 39-06-22541445; E-mail: d.santini{at}unicampus.it

Received 2/ 5/03; accepted 3/26/03.

REFERENCES

1. Corey E., Brown L. G., Quinn J. E., Poot M., Roudier M. P., Higano C. S., Vessella R. L. Zoledronic acid exhibits inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer. Clin. Cancer Res., 9: 295-306, 2003.[Abstract/Free Full Text]
2. Lee M. V., Fong E. M., Singer F. R., Guenette R. S. Bisphosphonate treatment inhibits the growth of prostate cancer cells. Cancer Res., 61: 2602-2608, 2001.[Abstract/Free Full Text]
3. Fournier P., Boissier S., Filleur S., Guglielmi J., Cabon F., Colombel M., Clezardin P. Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res., 62: 6538-6544, 2002.[Abstract/Free Full Text]
4. Saad F., Gleason D. M., Murray R., Tchekmedyian S., Venner P., Lacombe L., Chin J. L., Vinholes J. J., Goas J. A., Chen B., Zoledronic Acid Prostate Cancer Study Group. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J. Natl. Cancer Inst. (Bethesda), 94: 1458-1468, 2002.[Abstract/Free Full Text]

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