IMPORTANCE Zoledronic acid, a third-generation aminobisphosphonate, reduces the incidence of skeletal-related events and pain in patients with bone metastases. The optimal dosing interval for zoledronic acid is uncertain.OBJECTIVE To determine whether zoledronic acid administered every 12 weeks is noninferior to zoledronic acid administered every 4 weeks. DESIGN, SETTING, PARTICIPANTS Randomized, open-label clinical trial conducted at 269 academic and community sites in the United States. Patients (n = 1822) with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma who had at least 1 site of bone involvement were enrolled between May 2009 and April 2012; follow-up concluded in April 2014.INTERVENTIONS Patients were randomized to receive zoledronic acid administered intravenously every 4 weeks (n = 911) vs every 12 weeks (n = 911) for 2 years. MAIN OUTCOMES AND MEASURESThe primary end point was the proportion of patients having at least 1 skeletal-related event (defined as clinical fracture, spinal cord compression, radiation to bone, or surgery involving bone) within 2 years after randomization and a between-group absolute difference of 7% as the noninferiority margin. Secondary end points included the proportion of patients with at least 1 skeletal-related event by disease type, pain as assessed by the Brief Pain Inventory (range, 0-10; higher scores indicate worse pain), Eastern Cooperative Oncology Group performance status (range, 0-4; higher scores indicate worse disability), incidence of osteonecrosis of the jaw, kidney dysfunction, skeletal morbidity rate (mean number of skeletal-related events per year), and, in a subset of 553 patients, suppression of bone turnover (assessed by C-terminal telopeptide levels). RESULTS Among 1822 patients who were randomized (median age, 65 years; 980 [53.8%] women; 855 with breast cancer, 689 with prostate cancer, and 278 with multiple myeloma), 795 completed the study at 2 years. A total of 260 patients (29.5%) in the zoledronic acid every 4-week dosing group and 253 patients (28.6%) in the every 12-week dosing group experienced at least 1 skeletal-related event within 2 years of randomization (risk difference of −0.3% [1-sided 95% CI, −4% to ϱ]; P < .001 for noninferiority). The proportions of skeletal-related events did not differ significantly between the every 4-week dosing group vs the every 12-week dosing group for patients with breast cancer, prostate cancer, or multiple myeloma. Pain scores, performance status scores, incidence of jaw osteonecrosis, and kidney dysfunction did not differ significantly between the treatment groups. Skeletal morbidity rates were numerically identical in both groups, but bone turnover was greater (C-terminal telopeptide levels were higher) among patients who received zoledronic acid every 12 weeks.CONCLUSIONS AND RELEVANCE Among patients with bone metastases due to breast cancer, prostate cancer, or multiple myeloma, the use of zoledronic acid every 12 weeks compared with the standard dosing interval of every 4 we...
Colorectal cancer (CRC) is the third most common cancer in the United States, with more than 102,000 new patients diagnosed per year. 1 It is, however, one of the few cancers that is highly preventable through the use of routine screening, 2 which can also prevent death resulting from CRC. 3,4 CRC is also one cancer that continues to demonstrate widening incidence and survival disparities between whites and African Americans. 1,5 Although the reasons for these disparities are multifactorial, advanced stage at diagnosis may explain up to 50% of the survival disparity. 6 This reality is not unique to CRC. Those who are poor, underserved, or minorities are more likely to get cancer and die as a result of it than those who are rich or white. This is a fact, and it is the current reality of cancer care in the United States, as documented in thousands of peer-reviewed articles, including the focus of an Institute of Medicine report. 6a The shame for CRC is that the higher incidence rates and advanced stage of diagnosis are likely affected by differences in screening rates between whites and racial and ethnic minority populations. Multiple studies have documented lower rates of up-to-date screening among minority patients as well as lower rates of screening with colonoscopy. 7-11 Other studies have also found lower rates of follow-up for abnormalities detected on screening among minorities. 12 Lack of insurance and usual sources of care certainly contribute to these disparities, but even when screening is universally provided, such as in the Medicare program, screening rates and follow-up after abnormal findings are still lower among African Americans compared with whites. 7,13,14 Several randomized trials have demonstrated that provision of CRC screening combined with outreach efforts can significantly increase CRC screening rates among minority populations. 15-19 Moreover, patient navigation can increase the proportion of patients who receive appropriate and timely follow-up for abnormalities and facilitate the timely start of treatment. 20-22 In Journal of Clinical Oncology, Robbins et al 23 reported on a study that identified disparities in CRC mortality rates among African American patients with late-stage disease. In an editorial, Paskett 24 suggested three steps to reduce CRC disparities: one, increase CRC
Introduction: Many challenges to clinical trial accrual exist,
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