Abstract
Introduction: Approximately 85% of patients who die from prostate cancer present the spread of bone metastases. Even though the radiological appearance of such metastases is osteoblastic, it is now known that these lesions coexist in their microenvironment with blastic and lytic lesions. The process always begins with bone lysis by osteoclast proliferation, paralleling nearby bone deposition. The treatment options are palliative and have poor clinical response with short-lived improvement. We have studied the clinical effect of bisphosphonates (clodronate) in the treatment of skeletal complications from prostate cancer.
Materials and Methods: In an open prospective study, 58 patients with hormone-refractory prostate cancer with bone metastases were assessed from November 2000 to September 2003. The mean age was 70.3 y (range: 51–87 y). Bone scintigraphy, plain X-ray, assaying of prostate-specific antigen (PSA) and biochemical tests were requested before and following treatment. Patients were previously and subsequently assessed using the visual pain scale (0–10) and Karnofsky's index after the first and second intravenous (i.v.) infusions (administration of i.v. clodronate every 28 days) and every 4–6 months thereafter. Student's t-test was used for statistical analysis.
Results: A total of 53 patients (91.4%) showed improvement after the first and/or second cycle, which persisted for at least 4 months (average 6.3 months). The averages on the visual pain scale improved from 7.4 (range: 2–8) to 2.4 (0–7) and on Karnofsky's index from 43 (32–58) to 73 (50–82). The radiological appearance of the metastases improved in 27 patients (46.5%) and there were few relapses (six patients; 10.3%).
Conclusions: Clodronate was effective in the treatment of skeletal complications from prostate cancer. There was an objective response in 91.4% of treated patients, with a marked improvement in the subjective visual pain scale evaluation as well as on Karnofsky's index, with low side effects.
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References
Berruti A et al. Incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease: predictive role of bone resorption and formation markers evaluated at baseline. J Urol 2000; 164: 1248–1253.
Greenlee RT, Murray T, Bolden S . Cancer statistics, 2000. American Cancer Society, January/February 2000; 50: 6–11.
Parker SL, Tong T, Bolden S . Cancer statistics 1997. Cancer J Clin 1997; 47: 5–6.
Issacs JT . The biology of hormone refractory prostate cancer. Why does it develop? Urol Clin North Am 1999; 26: 263–269.
Smith Jr JA, Soloway MS, Young MJ . Complications of advanced prostate cancer. Urology 1999; 54: 8–12.
Guise TA, Mundy GR . Cancer and bone. Endocr Rev 1998; 19: 18–54.
Dodwell DJ . Malignant bone resorption: cellular and biochemical mechanisms. Ann oncol 1992; 3: 257–267.
Powles T et al. Controled trial of clodronate in patient with primary operable breast cancer. J Clin Oncol 2002; 20: 3219–3224.
Orr F, Lee J, Duivenvoorden WC . Pathophysiologic interactions in skeletal metastasis. Cancer, Suppl 2000; 88: 2912–2915.
Sansoni P, Passeri G, Fangnoni F . Inhibition of antigen presenting and cell function by alendronate in vitro. J. Bone Miner Res 1995; 10: 1719–1723.
Lissoni P, Cazzanigna M, Barni, Derenne S . Acute effect of pamidronate administration on serum levels of interleukin-6 in advanced solid tumor patients with bone metastases and their possible implications in the immunotherapy of cancer with interleukin-2. Eur J Cancer 1992; 33: 304–308.
Diel IJ, Solomayer EF, Costa SD . Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med 1998; 339: 357–363.
Luckman SP, Huges DE, Loxon FF . Nitrogen containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins including Ras. J Bone Miner Res 1998; 13: 581–589.
Adami S, Salvagno G, Guarrera G . Dichloromethylene—biphosphonate in patients with prostatic carcinoma metastatic to the skeleton. J Urol 1985; 134: 1152–1155.
Vorreuther R . Biphosphonates as an adjunct to palliative therapy of bone metastases from prostatic carcinoma. A pilot study on clodronate. Br J Urol 1993; 72: 792–795.
Heidenreich A, Hofmann R, Engelmann UH . The use of bisphosphonate for the palliative treatment of painful bone metastasis due to hormone refractory prostate cancer. J Urol 2001; 165: 136–140.
Dearnaley DP et al. A double-blind, placebo-controlled, randomized trial of oral sodium clodronate for metastatic prostate cancer (MRC PR05 Trial). J Natl Cancer Inst 2003; 95: 1300–1311.
Munoy GR . Bisphosphonates and tumor burden. J Clin Oncol 2002; 20: 3191–3192.
Smith Jr JA . Palliation of painful bone metastases from prostate cancer using sodium etidronate: results of randomized, prospective, double-blind placebo controlled study. J Urol 1989; 141: 85–87.
Jagdev SP et al. Comparison of effects of intravenous pamidronate and oral clodronate on symptoms and bone resorption with metastatic bone disease. Ann Oncol 2001; 12: 1433–1438.
Ernst DS et al. Randomized, double-blind, controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/predinisone and placebo in patients with hormone-refractory prostate cancer and pain. J Clin Oncol 2003; 21: 3335–3342.
Saad F et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002; 94: 1458–1468.
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Rodrigues, P., Hering, F. & Campagnari, J. Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients. Prostate Cancer Prostatic Dis 7, 350–354 (2004). https://doi.org/10.1038/sj.pcan.4500752
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DOI: https://doi.org/10.1038/sj.pcan.4500752
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