A multicenter, retrospective epidemiologic survey of the clinical features and management of bone metastatic disease in China

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Abstract

Background

Bone metastases are common in patients with advanced cancer. Bisphosphonates (BPs) could prevent or delay the development of skeleton-related events (SREs). The present study aimed to identify the clinical features of and treatment strategies for Chinese patients with bone metastases.

Methods

Consecutive cancer patients who had bone metastases and received BP treatment were enrolled. A questionnaire was developed to collect the patients’ clinical data, as well as information on the diagnosis and management of bone metastases. Physicians’ awareness of the guidelines and knowledge of the application of BP were also assessed.

Results

A total of 3223 patients with lung cancer (36.5%), breast cancer (30.9%), prostate cancer (8.5%), and gastrointestinal cancer (5.7%) were included in this study. The sites of bone metastases were the thoracic spine (56.0 %), lumbar spine (47.1%), ribs (32.6%), and pelvis (23.2%). The SRE frequency was the highest in patients with multiple myeloma (36.6%), followed by those with lung cancer (25.9%), breast cancer (20.2%), prostate cancer (18.2%), and gastrointestinal cancer (17.3%). Irradiation to the bone was the most frequent SRE (58% in lung cancer patients, 45% in breast cancer patients, and 48% in prostate cancer patients). Our survey also showed that 45.5% of patients received BP within 3 months after their diagnosis of bone metastases, whereas the remaining 54.5% of patients did not receive BP treatment until at least 3 months after their diagnosis of bone metastases. The SRE frequency in the former group was significantly lower than that in the latter group (4.0% vs. 42.3%, P < 0.05). In patients with more than 6 months of continuous BP treatment, the mean time to the first SRE was significantly longer than that in patients with less than 6 months of continuous BP treatment (7.2 vs. 3.4 months, P < 0.05). In addition, 12.2% of the physicians were not aware of the efficacy of BP in preventing and delaying SRE. Only half (52.3%) of the physicians agreed that the BP treatment should persist for at least 6 months unless it was intolerable.

Conclusions

Our study suggested that prompt and persistent BP treatment was associated with a reduced risk of SREs. However, our survey also revealed that the proper application of BP was not as common as expected in China.

Electronic supplementary material

The online version of this article (doi:10.1186/s40880-016-0102-6) contains supplementary material, which is available to authorized users.

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First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial

Gareth J. Morgan, Faith Davies, Walter Gregory … (2010)

Summary Background Bisphosphonates reduce the risk of skeletal events in patients with malignant bone disease, and zoledronic acid has shown potential anticancer effects in preclinical and clinical studies. We aimed to establish whether bisphosphonates can affect clinical outcomes in patients with multiple myeloma. Methods Patients of age 18 years or older with newly diagnosed multiple myeloma were enrolled from 120 centres in the UK. Computer-generated randomisation sequence was used to allocate patients equally, via an automated telephone service, to receive 4 mg zoledronic acid as an infusion every 3–4 weeks or 1600 mg oral clodronic acid daily. Patients also received intensive or non-intensive induction chemotherapy. No investigators, staff, or patients were masked to treatment allocation, and bisphosphonate and maintenance therapy continued at least until disease progression. The primary endpoints were overall survival, progression-free survival, and overall response rate. We assessed between-group differences with Cox proportional hazards models for progression-free survival and overall survival, and with logistic regression models for overall response rate. Analysis was by intention to treat. This trial is registered, number ISRCTN68454111. Findings 1970 patients were enrolled between May, 2003, and November, 2007, of whom 1960 were eligible for intention-to-treat analysis: 981 in the zoledronic acid group (555 on intensive chemotherapy, 426 on non-intensive chemotherapy); and 979 on clodronic acid (556 on intensive chemotherapy, 423 on non-intensive chemotherapy). The treatment cutoff was Oct 5, 2009, with patients receiving bisphosphonates for a median of 350 days (IQR 137–632) before disease progression, with a median of 3·7 years' follow-up (IQR 2·9–4·7). Zoledronic acid reduced mortality by 16% (95% CI 4–26) versus clodronic acid (hazard ratio [HR] 0·84, 95% CI 0·74–0·96; p=0·0118), and extended median overall survival by 5·5 months (50·0 months, IQR 21·0 to not reached vs 44·5 months, IQR 16·5 to not reached; p=0·04). Zoledronic acid also significantly improved progression-free survival by 12% (95% CI 2–20) versus clodronic acid (HR 0·88, 95% CI 0·80–0·98; p=0·0179), and increased median progression-free survival by 2·0 months (19·5 months, IQR 9·0–38·0 vs 17·5 months, IQR 8·5–34·0; p=0·07). Rates of complete, very good partial, or partial response did not differ significantly between the zoledronic acid and clodronic acid groups for patients receiving intensive induction chemotherapy (432 patients [78%] vs 422 [76%]; p=0·43) or non-intensive induction chemotherapy (215 [50%] vs 195 [46%]; p=0·18). Both bisphosphonates were generally well tolerated, with similar occurrence of acute renal failure and treatment-emergent serious adverse events, but zoledronic acid was associated with higher rates of confirmed osteonecrosis of the jaw (35 [4%]) than was clodronic acid (3 [<1%]). Interpretation Consistent with the potential anticancer activity of zoledronic acid, overall survival improved independently of prevention of skeletal-related events, showing that zoledronic acid has treatment benefits beyond bone health. These findings support immediate treatment with zoledronic acid in patients with newly diagnosed multiple myeloma, not only for prevention of skeletal-related events, but also for potential antimyeloma benefits. Funding Medical Research Council (London, UK), with unrestricted educational grants from Novartis, Schering Health Care, Chugai, Pharmion, Celgene, and Ortho Biotech.

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The updated incidences and mortalities of major cancers in China, 2011

Wanqing Chen, Rongshou Zheng, Hongmei Zeng … (2015)

Introduction The National Central Cancer Registry (NCCR) of China collected population-based cancer registration data from all cancer registries in China. This study aimed to compile national cancer incidences and mortalities in 2011 and estimate cancer incident new cases and cancer deaths. Methods In 2014, there were 234 cancer registries that submitted records of new cancer cases and cancer deaths that occurred in 2011 to the NCCR. All datasets were evaluated based on the criteria of data quality of the NCCR. The data of 177 registries was of sufficient quality and was compiled to evaluate cancer statistics in 2011. The pooled data were stratified by area, sex, age group, and cancer type. Cancer incident cases and deaths were estimated using age-standardized rates (ASR) and the Chinese population. All incidences and mortalities were age-standardized to the 2000 Chinese standard population and Segi’s population. Results The estimates of new cancer incident cases and cancer deaths were 3,372,175 and 2,113,048 in 2011, respectively. The crude incidence was 250.28/1,00,000 (277.77/1,00,000 for males and 221.37/1,00,000 for females). The ASRs of incidence by the Chinese standard population (ASRIC) and by the world standard population (ASRIW) were 186.34/1,00,000 and 182.76/1,00,000, respectively, with a cumulative incidence (0–74 years old) of 21.20%. Cancers of the lung, female breast, stomach, liver, colorectum, esophagus, cervix, uterus, prostate, and ovary were the most common cancers, accounting for approximately 75% of all new cancer cases. Lung, liver, gastric, esophageal, colorectal, female breast, pancreatic, brain, and cervical cancers and leukemia were the leading causes of cancer death, accounting for approximately 80% of all cancer deaths. Cancer incidence, mortality, and spectrum were all different between urban and rural areas and between males and females. Conclusions The population covered by the cancer registries greatly increased from 2010 to 2011. The data quality and representativeness of cancer registries have gradually improved. Cancer registries have an irreplaceable role in research on cancer prevention and control. The disease burden of cancer is increasing, and the health department must implement effective measures to contain the increased cancer burden in China.

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Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials.

Jimmy R. Theriault, J. Simeone, James D R Knight … (2000)

Pamidronate therapy previously has been shown to reduce skeletal complications effectively for up to 12 months in breast carcinoma patients with bone metastases. The current study data provide further follow-up results regarding the effects of long term (up to 24 months) pamidronate treatment in women with breast carcinoma and osteolytic metastases. Follow-up results from two prospective, multicenter, randomized, double-blind, placebo-controlled intervention trials conducted at academic and community oncology centers were combined to provide a large data set with which to evaluate the long term efficacy and safety of pamidronate therapy. Seven hundred fifty-four women with Stage IV breast carcinoma and osteolytic metastases were randomized to the 2 treatment arms of the trial. Three patients were excluded from the intent-to-treat population for the analysis. A total of 751 evaluable patients were randomized to receive either a 90-mg intravenous pamidronate infusion (367 patients) or a placebo infusion (384 patients) every 3-4 weeks. The primary outcome measures were skeletal morbidity rate (events/year), proportion of patients developing a skeletal complication, and time to first skeletal complication. Of the 367 women receiving pamidronate, 115 (31.3%) completed the trial and 81 (22.1%) discontinued the study due to adverse events. Of the 384 women who received placebo, 100 (26.0%) completed the study and 76 (19.8%) discontinued the study due to adverse events. The skeletal morbidity rate was 2.4 in the pamidronate group and 3.7 in the placebo group (P < 0.001). In the pamidronate group, 186 of the 367 patients (51%) had skeletal complications compared with 246 of the 384 patients in the placebo group (64%) (P < 0.001). The median time to first skeletal complication was 12.7 months in the pamidronate group and 7 months in the placebo group (P < 0.001). Six patients treated with pamidronate discontinued treatment due to drug-related adverse events. Pain and analgesic scores were significantly worse in the placebo group compared with those patients in the pamidronate group. In the current study, monthly infusions of 90 mg of pamidronate as a supplement to antineoplastic therapy were found to be well tolerated and superior to antineoplastic therapy alone in preventing skeletal complications and palliating symptoms for at least 24 months in breast carcinoma patients with osteolytic bone metastases. Copyright 2000 American Cancer Society.

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Author and article information

Contributors

Yunpeng Yang: yangyp@sysucc.org.cn

Yuxiang Ma: mayx@sysucc.org.cn

Jin Sheng: shengjin@sysucc.org.cn

Yan Huang: huangyan@sysucc.org.cn

Yuanyuan Zhao: zhaoyy@sysucc.org.cn

Wenfeng Fang: fangwf@sysucc.org.cn

Shaodong Hong: hongshd@sysucc.org.cn

Ying Tian: tianying@sysucc.org.cn

Cong Xue: xuecong@sysucc.org.cn

Li Zhang: +86-20-87343458 , zhangli63@hotmail.com

Journal

Journal ID (nlm-ta): Chin J Cancer

Journal ID (iso-abbrev): Chin J Cancer

Title: Chinese Journal of Cancer

Publisher: BioMed Central (London )

ISSN (Print): 1000-467X

ISSN (Electronic): 1944-446X

Publication date (Electronic): 25 April 2016

Publication date PMC-release: 25 April 2016

Publication date Collection: 2016

Volume: 35

Electronic Location Identifier: 40

Affiliations

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060 Guangdong P. R. China

Article

Publisher ID: 102

DOI: 10.1186/s40880-016-0102-6

PMC ID: 4845386

PubMed ID: 27112196

SO-VID: 846c31bb-ff5f-47e3-8f93-6dff9c55bc52

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 16 August 2015

Date accepted : 26 January 2016

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Keywords: bisphosphonates,bone metastases,skeleton-related events,chinese cancer patients

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Keywords: bisphosphonates, bone metastases, skeleton-related events, chinese cancer patients

A multicenter, retrospective epidemiologic survey of the clinical features and management of bone metastatic disease in China

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Most cited references 13

First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial

The updated incidences and mortalities of major cancers in China, 2011

Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials.

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