Effects of Long-Term Intravenous Ibandronate Therapy on Skeletal-Related Events, Survival, and Bone Resorption Markers in Patients With Advanced Multiple Myeloma

Menssen, Hans D.; Sakalová, A; Fontana, A; Herrmann, Zuzana; Boewer, C; Facon, Thierry; Личиницер, М. Р.; Singer, Charles R.J.; Euller‐Ziegler, Liana; Wetterwald, Marc; Fière, D; Hrubisko, M; Thiel, Eckhard; Delmas, Pierre D.

doi:10.1200/jco.2002.02.032

Cited by 145 publications

(80 citation statements)

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“…Serum markers are especially convenient as blood is often being taken for other purposes (though diurnal variation is a problem for serum) and serum measurement avoids complex urine collection and creatinine correction. A recent study of ibandronate in multiple myeloma (Menssen et al, 2002) demonstrated that patients experienced significantly fewer skeletal-related events per patient year when the ibandronate dose selected effectively suppressed the bone turnover markers serum osteocalcin and urinary Ctx. This study also found that patients experiencing a defined reduction in both bone markers suffered fewer events than in those with reduction in only one marker, raising the possibility that an index comprising more than one bone marker may add further predictive value.…”

Section: Discussionmentioning

confidence: 99%

“…However, with few exceptions (Lipton et al, 1998;Menssen et al, 2002), little work has been carried out on the possible correlation between bone markers and the occurrence of skeletal events in metastatic bone disease. If such a link can be firmly established, then it may be appropriate to direct the management of patients with metastatic bone disease to maintain or lower an individual's bone marker values into the normal range.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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Bone resorption predicts for skeletal complications in metastatic bone disease

et al. 2003

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“…71 Bone markers during anti-resorptive therapy Biochemical markers of bone turnover have been used in MM both to monitor bisphosphonate treatment, and to determine 71 Terpos et al showed that the addition of pamidronate to CC significantly reduced urinary NTX and disease-related pain compared with CC alone, 49 and that pamidronate in combination with interferon-a induced bone formation in MM patients at plateau phase. 61 Ibandronate at a dose of 2 mg showed a substantial reduction of CTX and OC in only one-third of MM patients, 74 whereas in a randomized study, monthly pamidronate (90 mg, IV) produced a greater reduction of NTX and TRACP-5b compared with monthly ibandronate (4 mg, IV). 56,75 In a large, randomized study comparing 4 mg zoledronic acid with 90 mg pamidronate, given IV every 3-4 weeks in patients with bone metastases from breast cancer or with MM osteolytic disease, urinary NTX was strongly suppressed (up to 64% below baseline in both treatment groups) for the duration of the study.…”

Section: Correlations Of Bone Turnover Markers With Myeloma Activity mentioning

confidence: 99%

The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

et al. 2010

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Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic lesions rarely heal and X-rays are of limited value in monitoring bone destruction during antimyeloma or anti-resorptive treatment. Biochemical markers of bone resorption (amino-and carboxy-terminal cross-linking telopeptide of type I collagen (NTX and CTX, respectively) or CTX generated by matrix metalloproteinases (ICTP)) and bone formation provide information on bone dynamics and reflect disease activity in bone. These markers have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX and serum ICTP are elevated in myeloma patients with osteolytic lesions and correlate with advanced disease stage. Furthermore, urinary NTX and serum ICTP correlate with risk for skeletal complications, disease progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti-myeloma therapies and provides information on novel markers that may be of particular interest in the near future.

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“…ibandronate does not appear to compromise renal safety, including in patients with urologic cancer and compensated renal insufficiency [51]. Few studies have investigated the efficacy of ibandronate in patients with MM [52,53]. However, available data suggest that ibandronate is well tolerated in this indication, even in elderly patients with pre-existing renal failure [53,54].…”

Section: Ibandronatementioning

confidence: 99%

The Use of Bisphosphonates in Elderly Cancer Patients

Gridelli

2007

The Oncologist

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LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Discuss the role of bisphosphonate therapy in the management of metastatic bone disease.2. Describe the differences between individual bisphosphonates with regard to safety and route of administration.3. List the reasons for including elderly patients in clinical trials of bisphosphonates for the management of metastatic bone disease.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTAs life expectancy increases throughout the 21st century, the size of the elderly population will also expand. This will have a marked effect on the number of patients with cancer who are classified as elderly. Despite this, the design of most clinical studies of cancer therapies excludes those patients who are >70 years of age.Bisphosphonates are an example of a cancer therapy that has not been examined in randomized clinical trials of elderly patients. These agents are used for the prevention of skeletal complications and the relief of bone pain in patients with bone metastases. When deciding which bisphosphonate to prescribe to an elderly patient, each drug should be considered on its individual merits. Examples of areas of concern with bisphosphonates in elderly patients include their relative renal safety profiles and propensity for osteonecrosis of the jaw. Another consideration when choosing the most appropriate formulation is the preferred method of administration (oral or i.v.), which may affect patient compliance with therapy.As the use of bisphosphonates increases, the need for data on their use in elderly patients also becomes greater. Clinical trials of bisphosphonates in this patient population are currently under way, and their results are keenly awaited. The Oncologist 2007;12:62-71

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Effects of Long-Term Intravenous Ibandronate Therapy on Skeletal-Related Events, Survival, and Bone Resorption Markers in Patients With Advanced Multiple Myeloma

Abstract: Monthly injections of ibandronate 2 mg IV neither reduced bone morbidity nor prolonged survival in the overall population of stage II/III multiple myeloma patients.

Cited by 145 publications

References 28 publications

Bone resorption predicts for skeletal complications in metastatic bone disease

Bone resorption predicts for skeletal complications in metastatic bone disease

The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

The Use of Bisphosphonates in Elderly Cancer Patients

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