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Background: Zoledronic acid (ZOL) is an important component of therapy for patients with metastatic bone disease (MBD) to reduce the risk of skeletal-related events (SREs). We evaluated overall survival (OS) in patients with MBD secondary to solid tumours included in placebocontrolled ZOL trials. Patients and methods: Exploratory analyses were performed using databases from three randomised trials of ZOL versus placebo. 1126 patients (ZOL, n=731; placebo, n=395) with complete baseline data for 18 predefined parameters were evaluated for OS. Relative risks (RRs) with 95% confidence intervals were assessed using stratified and adjusted Cox regression models. Baseline covariates defining patient populations with significantly different effects of ZOL treatment on OS (identified by stepwise backward elimination) were included in multivariate models. Results: Although OS was similar between the overall treatment groups, ZOL significantly improved OS in the subset of patients (n=423; 38%) with elevated baseline NTX ( >= 100 nmol/mmol creatinine; RR, 0.692; P=.0028). Notably, this effect was independent of SRE prevention. Additional covariates associated with OS benefits with ZOL (e.g., low albumin, SRE history, elevated lactate dehydrogenase, shorter cancer duration) were characteristic of advanced disease. Conclusion: These exploratory analyses suggest a beneficial effect of ZOL on OS in patients with highly aggressive or advanced MBD. (C) 2013 Elsevier GmbH. All rights reserved.

Biochemical markers of bone turnover provide insight into ongoing rates of skeletal metabolism and tumor-bone interactions in patients with malignant bone disease. This article reviews the available recent evidence assessing the potential of bone markers for detecting and monitoring malignant bone lesions in patients with advanced cancers, and for assessing overall skeletal health and response to antiresorptive therapies in patients at all stages of cancer progression. Most data thus far are for urinary N-terminal cross-linked telopeptide of type I collagen (NTX) in predicting risks of skeletal morbidity and death and monitoring response to zoledronic acid in patients with bone metastases. Ongoing studies are evaluating such correlations for other markers and therapies. Emerging evidence suggests that bone markers may help identify patients at high risk for bone metastasis or bone lesion progression, thereby allowing improved follow-up. Results from ongoing clinical trials evaluating such potential applications of bone markers are awaited. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Costs or benefits which accumulate for individuals over time are of interest in many life history processes. Familiar examples include costs of health care for persons with chronic medical conditions, the payments to insured persons during periods of disability, and quality of life which is sometimes used in the evaluation of treatments in terminally ill patients. For convenience, here we use the term costs to refer to cost or other cumulative measures. Two important scenarios are (i) where costs are associated with the occurrence of certain events, so that total cost accumulates as a step function, and (ii) where individuals may move between various states over time, with cost accumulating at a constant rate determined by the state occupied. In both cases, there is frequently a random variable T that represents the duration of the process generating the costs. Here we consider estimation of the mean cumulative cost over a period of interest using methods based upon marginal features of the cost process and intensity based models. Robustness to adaptive censoring is discussed in the context of the multi-state methods. Data from a quality of life study of breast cancer patients are used to illustrate the methods.