健保通過新藥 denosumab: 改善骨轉移的疼痛、增加骨頭硬度 !!!

抗癌 第4期乳癌病患的五年存活率，可達20%以上！鉅亨網新聞中心(來源：中廣新聞網)2014-02-1115:15 乳癌病人最常發生癌症骨轉移的狀況。根據統計，第四期乳癌發生骨轉移的機率最高達八成，遠超過肺、肝、腦等部位的轉移；透過妥適治療，第四期乳癌的五年存活率，可達20%，患者不要輕言放棄！長庚醫院乳房外科主任陳訓徹表示，乳癌發生骨轉移，初期症狀輕微，患者容易忽略而延誤治療，骨頭疼痛是骨轉移最常見的臨床症狀，常有腰椎、大腿骨、頭蓋骨、肋骨疼痛，這也是癌症骨轉移的警訊，起因於癌細胞促使骨細胞侵蝕作用旺盛，嚴重的會造成劇烈骨痛與骨折，嚴重影響病患生活。陳訓徹強調必須定期追蹤，只要發現骨轉移機會比較高的族群，就會選擇進行骨頭掃瞄，及早發現骨轉移的徵兆，提早一年至半年就介入治療，治療成功的機會就大幅提高。如果等到出現骨頭疼痛症狀，這時會發生高血鈣、也容易產生骨折等現象。甚有人會痛到必須施打嗎啡止痛，如果轉移到脊椎，常會壓迫神經引起骨頭痠痛麻，甚至半身不遂。陳訓徹表示，目前治療骨轉移常使用雙磷酸鹽或健保局今年初通過新藥癌骨瓦（denosumab），這兩種藥除了都可以改善骨轉移的疼痛、增加骨頭硬度外，也可以減少後續併發症，如骨折、脊椎壓迫、高血鈣等問題。陳訓徹說，比較這兩種藥，癌骨瓦作用機轉為單株抗體，可抑制蝕骨細胞作用，如同骨轉移的標靶治療，比較不會產生急性症狀。另外，針對腎功能不佳的病患，使用雙磷酸鹽就必須減低劑量或拉長打針時間，而使用癌骨瓦就不會影響腎臟的功能。據行政院衛福部的統計資料顯示，乳癌在國內女性死因排名第四，民國101年中就有近兩千名女性死於乳癌。長庚醫院乳房外科主任陳訓徹指出，乳癌的治療，應致力提高初期病的治癒率，對於第四期乳癌病人，希望能提升五年存活率。陳訓徹表示，對已發生轉移的乳癌病人來說，早先的臨床研究發現五年存活率只有7%，目前第四期乳癌病患的五年存活率，都可提升到20%以上，因此，已經發生轉移的乳癌病患不應放棄希望，應該積極接受治療，以維持好的生活品質。

 

Approved to increase bone mass in patients at high risk for fracture including androgen deprivation therapy (ADT) for nonmetastatic prostate cancer or adjuvant aromatase inhibitor (AI) therapy for breast cancer  On September 16, 2011, the FDA granted approval for denosumab (Prolia®, made by Amgen, Inc.) as a treatment to increase bone mass in patients who are at high risk of fracture from receiving androgen deprivation therapy (ADT) for nonmetastatic prostate cancer or adjuvant aromatase inhibitor (AI) therapy for breast cancer. In men with nonmetastatic prostate cancer, denosumab also reduced the incidence of vertebral fracture. Denosumab is a monoclonal antibody that binds to RANKL, a protein involved in the formation, function, and survival of osteoclasts, the cells responsible for bone resorption.  The approvals were based on results from two international randomized (1:1), double-blind, placebo-controlled trials in patients receiving ADT for nonmetastatic prostate cancer or adjuvant AI therapy for breast cancer. Trial 20040138 was a 3-year trial that enrolled 1,468 men with prostate cancer (median age 76 years). Men less than 70 years of age were required to have either a baseline bone mineral density (BMD) T-score at the lumbar spine, total hip, or femoral neck between -1.0 and -4.0, or history of osteoporotic fracture. Trial 20040135 was a 2-year trial that enrolled 252 women with breast cancer (median age 59 years). Women had a baseline BMD T-score at the lumbar spine, total hip, or femoral neck between -1.0 and -2.5 and had not experienced fracture after age 25. Patients were randomly assigned to receive subcutaneous injections of 60 mg denosumab or a placebo, once every 6 months, for a total of 6 doses in Trial 20040138 and for a total of 4 doses in Trial 20040135. The primary outcome measure in each trial was the percent change in lumbar spine BMD, from baseline to month 24 in Trial 20040138 and baseline to month 12 in Trial 20040135. A secondary outcome measure in Trial 20040138 was the incidence of new vertebral fractures through month 36. In Trial 20040138, the randomization was stratified by age (younger than 70 years vs. 70 years or older) and duration of ADT at trial entry (6 months or less vs. more than 6 months). Seventy nine percent received ADT for more than 6 months at trial entry. In Trial 20040135, the randomization was stratified by duration of adjuvant AI therapy at trial entry (6 months or less vs. more than 6 months). Sixty-two percent received adjuvant AI therapy for more than 6 months at trial entry. Denosumab resulted in a statistically significant effect on BMD compared with placebo in patients with nonmetastatic prostate or breast cancer, at 24 and 12 months respectively. In men with prostate cancer, denosumab also significantly reduced the incidence of new vertebral fractures at 36 months. At 36 months, the proportion of men with new vertebral fracture was 1.5 percent in men treated with denosumab compared with 3.9 percent in men treated with placebo [Absolute Risk Reduction (ARR) 2.4%, 95% CI (0.7, 4.1); Relative Risk Reduction (RRR) 62% (22, 81); p=0.0125].

Approved for unresectable giant cell tumor of bone in adults and skeletally mature adolescents  On June 13, 2013, the Food and Drug Administration (FDA) approved denosumab (Xgeva®  injection, Amgen Inc., for subcutaneous use) for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. Denosumab's approval was based on observation of durable objective responses in two multicenter open-label trials enrolling adult and skeletally mature adolescents with histologically confirmed, measurable giant cell tumor of bone. These tumors were recurrent, unresectable, or located where planned surgery was likely to result in severe morbidity. Patients received 120 mg denosumab subcutaneously every 4 weeks, with additional doses on days 8 and 15 of the first month. A total of 304 patients received denosumab. The median age was 33 years (range: 13-83 years) and a total of 10 patients were skeletally mature adolescents (13-17 years). Radiographic assessments at baseline and following denosumab treatment were available for 187 patients (61 percent). A retrospective determination of objective response was performed by an independent review committee using modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1).  An objective response was identified in 47 of 187 patients, for an overall response rate of 25 percent (95 percent confidence interval: 19, 32).  All responses were partial responses. The estimated median time to response was 3 months.  In the 47 patients with an objective response, the median duration of follow-up was 20 months (range: 2-44 months), and 51 percent (24 of 47) had responses lasting at least 8 months.  Three patients experienced disease progression following an objective response. Safety data were evaluated for 304 patients with giant cell tumor of bone who received at least one dose of denosumab. Of these patients, 145 were treated for at least 1 year. The most common adverse reactions were arthralgia, headache, nausea, back pain, fatigue, and pain in the extremity. The most common serious adverse reactions were osteonecrosis of the jaw and osteomyelitis. The recommended dose and schedule of denosumab for the treatment of giant cell tumor of bone is 120 mg administered subcutaneously every 4 weeks, with additional 120 mg doses on days 8 and 15 of the first month.