Comparison of the effects of intravenous pamidronate and oral clodronate on symptoms and bone resorption in patients with metastatic bone disease

Jagdev, Satinder; Purohit, O.P.; Heatley, Sarah; Herling, Christian; Coleman, Robert E.

doi:10.1023/a:1012506426440

Cited by 103 publications

(68 citation statements)

References 26 publications

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“…This may also explain the pain control obtained in a randomised controlled trial that favoured intravenous pamidronate over oral clodronato. 20 The severity of the disease may be an important issue for debate when 21 who failed to show improvement in pain control after adjuvant clodronate vs mitoxantrone. He had an analgesic response (450% decrease in analgesic intake from baseline) in 33% out of 104 cases using clodronate and 30% in the placebo group.…”

Section: Discussionmentioning

confidence: 99%

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

Rodrigues

Hering

Campagnari

2004

Prostate Cancer Prostatic Dis

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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.

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Section: Discussionmentioning

confidence: 99%

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

Rodrigues

Hering

Campagnari

2004

Prostate Cancer Prostatic Dis

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“…The majority of patients on the study received oral clodronate and this response rate is consistent with previous data with this drug. Higher biochemical response rates would be expected with more potent IV bisphosphonates (Vinholes et al, 1997;Jagdev et al, 2001). A proportion of the patients (approximately 21%) had already been on bisphosphonates prior to study entry and may have already achieved a biochemical response.…”

Section: Biochemical Response and Follow-up For Longer Than 6 Monthsmentioning

confidence: 99%

“…A study by Vinholes et al (1996) showed a significant correlation between metastatic bone pain and bone resorption. Several subsequent studies in both breast and prostate cancer patients have confirmed this initial finding (Jagdev et al, 2001). Both oral and intravenous bisphosphonate therapy have been shown to reduce Ntx levels and, importantly, only those patients who showed normalisation of bone resorption following bisphosphonate treatment experienced clinical benefit in terms of an improvement in pain, analgesic use and morbidity (Vinholes et al, 1997).…”

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confidence: 91%

Bone resorption predicts for skeletal complications in metastatic bone disease

et al. 2003

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Relationships between the rate of bone resorption (measured by urinary N-telopeptide (Ntx) excretion) and a range of skeletal complications have been evaluated in patients with metastatic bone disease. A total of 121 patients had monthly measurements of Ntx during treatment with bisphosphonates. All skeletal-related events, plus hospital admissions for bone pain and death during the period of observation, were recorded. Data were available for 121 patients over the first 3-month period of monitoring (0 -3 months) and 95 patients over the second 3-month period (4 -6 months). N-telopeptide levels were correlated with the number of skeletal-related events and/or death (r ¼ 0.62, Po0.001 for 0 -3 months and r ¼ 0.46, Po0.001 for 4 -6 months, respectively). Patients with baseline Ntx values X100 nmol mmol À1 creatinine (representing clearly accelerated bone resorption) were 19.48 times (95% CI 7.55, 50.22) more likely to experience a skeletal-related event/death during the first 3 months than those with Ntx o100 (Po0.001). In a multivariate logistic regression model, Ntx was highly predictive for events/death. This study is the first to indicate a strong correlation between the rate of bone resorption and the frequency of skeletal complications in metastatic bone disease. N-telopeptide appears useful in the prediction of patients most likely to experience skeletal complications and thus benefit from bisphosphonate treatment.

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“…In addition, the inhibitory activity of bisphosphonates on bone resorption may be indirectly mediated by other cells such as cells of the osteoblastic lineage or the macrophage family (Sahni et al, 1993;Nishikawa et al, 1996;Vitte et al, 1996;Siwek et al, 1997;Fromigue and Body, 2002). On the other hand, we and others (Fromigue et al, 2000;Senaratne et al, 2000;Jagdev et al, 2001b) previously showed that bisphosphonates can induce human breast cancer cell death in vitro (apoptosis and/or necrosis), which could contribute to their beneficial clinical effects. Thus, bisphosphonates exhibit beneficial effects on bone integrity by reducing bone resorption induced by osteoclasts and maybe also by direct 'antitumoral' effects.…”

mentioning

confidence: 92%

Bisphosphonates antagonise bone growth factors' effects on human breast cancer cells survival

2003

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Bone tissue constitutes a fertile 'soil' for metastatic tumours, notably breast cancer. High concentrations of growth factors in bone matrix favour cancer cell proliferation and survival, and a vicious cycle settles between bone matrix, osteoclasts and cancer cells. Classically, bisphosphonates interrupt this vicious cycle by inhibiting osteoclast-mediated bone resorption. We and others recently reported that bisphosphonates can also induce human breast cancer cell death in vitro, which could contribute to their beneficial clinical effects. We hypothesised that bisphosphonates could inhibit the favourable effects of 'bone -derived' growth factors, and indeed found that bisphosphonates reduced or abolished the stimulatory effects of growth factors (IGFs, FGF-2) on MCF-7 and T47D cell proliferation and inhibited their protective effects on apoptotic cell death in vitro under serum-free conditions. This could happen through an interaction with growth factors' intracellular phosphorylation transduction pathways, such as ERK1/2-MAPK. In conclusion, we report that bisphosphonates antagonised the stimulatory effects of growth factors on human breast cancer cell survival and reduced their protective effects against apoptotic cell death. Bisphosphonates and growth factors thus appear to be concurrent compounds for tumour cell growth and survival in bone tissue. This could represent a new mechanism of action of bisphosphonates in their protective effects against breast cancer-induced osteolysis.

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Comparison of the effects of intravenous pamidronate and oral clodronate on symptoms and bone resorption in patients with metastatic bone disease

Abstract: Intravenous pamidronate appears to be more effective than oral clodronate in both controlling symptoms and suppressing bone resorption.

Cited by 103 publications

References 26 publications

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

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

Bone resorption predicts for skeletal complications in metastatic bone disease

Bisphosphonates antagonise bone growth factors' effects on human breast cancer cells survival

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