Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients

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 hormonerefractory 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.

Bone-modifying agents in the treatment of bone metastases in patients with advanced genitourinary malignancies: a focus on zoledronic acid

“…Ernst et al 2003;Heidenreich et al 2005;Hering et al 2003;Rodrigues et al 2004;Saad and Eastham, 2010a;Saad et al 2004;Small et al 2003]. …”

“…It is therefore important to distinguish between BP use to preserve BMD during ADT or palliate pain from PC bone metastases and BP therapy to reduce the risk of SREs in patients with advanced CRPC. Zoledronic acid is the only BP approved for the latter purpose, although several BPs have demonstrated palliative benefits in patients with bone metastases from PC (Table 1) [Donat et al 2006;Ernst et al 2003;Heidenreich et al 2005;Hering et al 2003;Rodrigues et al 2004;Saad and Eastham, 2010a;Saad et al 2004;Small et al 2003]. …”

“…Bisphosphonate therapy interrupts the vicious cycle of increased osteolysis coupled with increased tumor growth, thereby preserving bone health and potentially delaying bone lesion progression [Mundy, 2002]. Several BPs have been evaluated in patients with bone metastases from GU malignancies [Donat et al 2006; Ernst et al 2003;Hatoum et al 2008Hatoum et al , 2011Hering et al 2003;Lipton et al 2002;Rodrigues et al 2004;Saad, 2008;Saad et al 2004]; although both oral and intravenous BPs have shown palliative activity in these settings, zoledronic acid (ZOL) is the only BP to have demonstrated significant objective and durable benefits and to have received broad regulatory approval for preventing SREs in patients with bone metastases from castration-resistant PC (CRPC) or other GU cancers (e.g. RCC and bladder cancer) [Lipton et al 2003;Saad et al 2002Saad et al , 2004 Zaghloul et al 2010].…”

Osteoclasts and Biomaterials

“…If implants can be used, they loosen due to particle-induced activation of osteoclasts [9] or osteoclasts lead to periprosthetic resorption, which in the worst case results in periprosthetic fracture [10]. The pain in metastatic bone disease seems to be mediated at least in part by osteoclastic action and can be alleviated by treatment with bisphosphonates [11]. Bone metastases use osteoclasts to spread inside bones [12].…”

Skeletal Related Events in Prostate Cancer: Important Therapeutic Considerations

“…Moreover, these substances can act as pain relief agents (Verreuther R, 1993;Rodrigues P, et al, 2004). Bisphosphonates, synthetic analogs of the endogenous pyrophosphate molecule, inhibit osteoclast-mediated bone destruction by a decrease bone resorption in patients receiving ADT and/or with metastatic disease (Smith MR, 2003;Ryan CW, et al, 2006;Lipton A, 2004).…”