Use of bisphosphonates in cancer patients

Body, Jean‐Jacques; Coleman, Robert E.; Piccart, Martine

doi:10.1016/s0305-7372(96)90020-1

Cited by 87 publications

(27 citation statements)

References 77 publications

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“…Bisphosphonates are the treatment of choice for hypercalcaemia of malignancy (Body et al, 1996) and have been shown to reduce skeletal complications in multiple myeloma (Berenson et al, 1996) and breast cancer (Hortobayi et al, 1996). They relieve metastatic bone pain caused by a variety of solid tumours, including prostate, with a consequent improvement in quality of life (Adami et al, 1985;Carey and Lippert, 1988;Coleman et al, 1996;Pelger et al, 1998).…”

Section: Resultsmentioning

confidence: 99%

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Garnero

Buchs

Zekri³

et al. 2000

Br J Cancer

215

128

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Prostate cancer is the most common malignancy in elderly men and is often complicated by osteosclerotic metastases. Bone scintigraphy is commonly used to assess the extent of bone metastases; its use is limited in monitoring of treatment efficacy because it is an expensive, time-consuming technique that does not reflect the rapid skeletal response to therapy (Coleman, 1998). The bone scan flare response following successful therapy also reduces the value of bone scanning in the early monitoring of treatment in prostate cancer (Pollen et al, 1984). The serum level of prostatespecific antigen is the most sensitive index of disease progression in most but not all patients, but does not reflect the effects of palliative treatments such as bisphosphonates for bone metastases in patients that escape from antihormonal therapy.The marked increase of osteoblastic activity in patients with osteosclerotic metastases is reflected by increased levels of serum total and bone-specific alkaline phosphatase (Pecherstorfer et al, 1995;Lorente et al, 1996). There is, however, biochemical (Myamoto et al, 1994, Sano et al, 1994Kylmala et al, 1995;Berruti et al, 1996;Ikeda et al, 1996;Takeuchi et al, 1996;Maeda et al, 1997;Nguyen-Pamart et al, 1997, Pelger et al, 1998 and histological (Urwin et al, 1985;Clarke et al, 1991) evidence of increased bone resorption in these patients even in the absence of overt osteolytic bone metastases. This increased bone resorption is of clinical relevance as it is the rationale for using bisphosphonates, a palliative treatment that has been shown to reduce bone pain in patients with progressive metastatic prostate cancer who no longer respond to hormonal therapy (Adami et al, 1985;Carey and Lippert, 1988;Clarke et al, 1992;Kylmala et al, 1993, Taube et al, 1994Pelger et al, 1998).In this study we assessed the level of bone resorption in patients with osteosclerotic metastases from prostate cancer before and after bisphosphonate treatment by using new sensitive and specific biochemical markers of bone resorption including a serum assay for type I collagen C-telopeptide breakdown products; and values were compared to those of bone formation markers. PATIENTS AND METHODSForty-eight patients with carcinoma of the prostate (age 71.7 ± 9.6 years, mean ± 1 s.d.) and nine with benign prostatic hyperplasia (BHP) (age 69.8 ± 4.2 years) were enrolled. All patients with cancer had a prostatic biopsy and tissue diagnosis of adenocarcinoma. Bone involvement and its extent was evaluated by bone scintigraphy using Technetium-99m labelled methylene bisphosphonate. When bone metastases were suspected, confirmation was obtained with standard radiographs, computerized tomography (CT) and/or magnetic resonance imaging. The metastatic load in Summary Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to tha...

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Section: Resultsmentioning

confidence: 99%

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Garnero

Buchs

Zekri³

et al. 2000

Br J Cancer

215

128

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“…Several small pilot studies encouraged investigators to evaluate either regular intravenous infusions of pamidronate, enteric-coated oral pamidronate, or either oral or parenteral clodronate in advanced breast cancer [18]. In addition to the effects on bone pain, sclerosis of lytic lesions was seen in phase II studies of intravenous pamidronate in the absence of specific anticancer treatments.…”

Section: Bisphosphonates As Adjunctive Therapy In Metastatic Bone Dismentioning

confidence: 99%

Management of Bone Metastases

Coleman

2000

The Oncologist

140

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Professor of Medical Oncology, Yorkshire Cancer Research Department of Clinical Oncology, Cancer Research Centre, Weston Park Hospital, Whitham Road, Sheffield, S10 2SJ England. Telephone: 44-0-114-226-5213; Fax: 44-0-114-226-5678; e-mail: r.e.coleman@sheffield.ac.uk. Received July 28, 2000; accepted for publication September 11, 2000. ©AlphaMed Press 1083-7159/2000.00/0 INTRODUCTIONThe skeleton is the most common organ to be affected by metastatic breast cancer, and the site of disease which produces the greatest morbidity. Skeletal morbidity includes pain requiring radiotherapy, hypercalcemia, pathological fracture, and spinal cord or nerve root compression. From randomized trials in advanced breast cancer [1,2], it can be seen that one of these major skeletal events occurs on average every three to four months. Additionally, metastatic disease may remain confined to the skeleton with the decline in quality of life and eventual death due entirely to skeletal complications.There is now a much greater understanding of the mechanisms underlying the development of bone metastases and the interdependence between cancer cells and bone. Tumor cells within the bone marrow cavity secrete a variety of paracrine factors that stimulate bone cell function (Fig. 1).

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“…The median survival is 2 years with 20% of patients remaining alive for 5 years after first recurrence in bone (Coleman and Rubens, 1987). In addition, a significant proportion of patients appear clinically to have disease confined to the skeleton, and these women die of the complications of metastatic bone disease, namely immobility, pathological fractures, hypercalcaemia of malignancy and bone marrow failure, with no evidence clinically of involvement at other metastatic sites.With the development of bisphosphonates as specific treatments for metastatic bone disease (Body et al, 1996), there is increased interest in identifying those patients who are most likely to benefit from bisphosphonate treatment. In addition, if prophylactic use of bisphosphonates proves able to influence the development of bone metastases, it will be important to identify those patients at greatest risk of bone involvement, particularly in isolation from other metastatic disease, so that treatment can be targeted rationally.…”

mentioning

confidence: 99%

“…With the development of bisphosphonates as specific treatments for metastatic bone disease (Body et al, 1996), there is increased interest in identifying those patients who are most likely to benefit from bisphosphonate treatment. In addition, if prophylactic use of bisphosphonates proves able to influence the development of bone metastases, it will be important to identify those patients at greatest risk of bone involvement, particularly in isolation from other metastatic disease, so that treatment can be targeted rationally.…”

mentioning

confidence: 99%

Clinical course and prognostic factors following bone recurrence from breast cancer

Coleman

Smith²,

Rubens³

1998

Br J Cancer

257

153

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Summary Three hundred and sixty-seven women presenting to the Breast Unit at Guy's Hospital between 1975 and 1990 whose first distant metastasis was in the skeleton were identified and the influence of a number of patient and tumour characteristics on the development and subsequent prognosis of bone metastases was assessed.One hundred and thirty-nine women had disease that remained clinically confined to the skeleton. They were more likely to be older, with lobular carcinoma and to have presented initially with little or no axillary lymph node involvement. The 228 women who subsequently developed disease at extra-osseus sites were more likely to have poorly differentiated ductal tumours and heavy lymph node involvement at primary diagnosis.On multivariate analysis, the clinical and pathological factors of greatest prognostic importance for survival after the development of bone metastases were histological grade (P = < 0.0001), oestrogen receptor status (P = < 0.0001), bone disease at initial presentation (P= < 0.0001), disease-free interval (P= 0.002) and age (P= 0.006).To enable a rational cost-effective use of bisphosphonates in metastatic bone disease, selection of patients with relatively indolent, bone-only disease for bisphosphonate therapy (as defined in this study) should be compared with the current licensed recommendation of unselected treatment for all patients with lytic bone metastases.Bone metastases are frequent in advanced breast cancer and often contribute to the cause of death. Like breast cancer affecting other organs, metastatic bone disease has an extremely variable prognosis. The median survival is 2 years with 20% of patients remaining alive for 5 years after first recurrence in bone (Coleman and Rubens, 1987). In addition, a significant proportion of patients appear clinically to have disease confined to the skeleton, and these women die of the complications of metastatic bone disease, namely immobility, pathological fractures, hypercalcaemia of malignancy and bone marrow failure, with no evidence clinically of involvement at other metastatic sites.With the development of bisphosphonates as specific treatments for metastatic bone disease (Body et al, 1996), there is increased interest in identifying those patients who are most likely to benefit from bisphosphonate treatment. In addition, if prophylactic use of bisphosphonates proves able to influence the development of bone metastases, it will be important to identify those patients at greatest risk of bone involvement, particularly in isolation from other metastatic disease, so that treatment can be targeted rationally. In this study, we have reviewed the clinical and tumour characteristics of patients developing first recurrence of breast cancer in bone and identified prognostic factors that predict for both survival and/or subsequent spread to other metastatic sites. PATIENTS AND METHODSThree hundred and sixty-seven women presenting to the Breast Unit at Guy's Hospital between 1975 and 1990 whose first distant metastasis was in the s...

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Use of bisphosphonates in cancer patients

Cited by 87 publications

References 77 publications

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Management of Bone Metastases

Clinical course and prognostic factors following bone recurrence from breast cancer

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