导读：多吉美－晚期肾癌首选的治疗药物，是一个双通道、多靶点的多激酶抑制剂，用于治疗晚期肾癌患者，显示出重要的抗肿瘤活性.

多吉美是一种新型的治疗晚期肾癌的小分子口服多激酶抑制剂，其主要成分是索拉非尼甲苯磺酸盐，该成分在临床前研究中显示了抗血管生成及抗细胞增殖的活性。2005年，多吉美作为10余年来首个被批准治疗晚期肾癌的新药上市，目前已在60多个国家获准用于该适应症的治疗。

作用机理
多吉美是一个双通道、多靶点的多激酶抑制剂。其通过抑制RAF/MEK/ERK通路中的丝氨酸/苏氨酸激酶RAF-11，抑制肿瘤细胞生长。另外，通过抑制VEGFR、PDGFR受体酪氨酸激酶抑制肿瘤血管生成。
多吉美既抑制肿瘤细胞生长又抑制肿瘤血管的生成，从而达到抑制肿瘤的目的。

服用方便快捷
多吉美为片剂，每片200mg，口服用药，推荐剂量为每日2次，每次2片。无需根据年龄，体质和体重的不同来调整剂量；建议空腹（饭前至少1小时或饭后2小时）服用，低脂饮食。

安全性及耐受性
I、II、III期单药临床试验的结果一致表明多吉美的毒性反应易于控制。发生频率最高的不良事件（皮肤、胃肠道及体质方面）的严重程度多为1/2级,可通过减量/中断治疗或对症治疗使之得到控制。3/4级的疲劳在多吉美组及安慰剂组的发生率相似。多吉美引起的血压增高在治疗早期即可出现，服用标准降压药物可使之得到普遍控制。与安慰剂组相比，多吉美治疗患者出血发生率稍高，但出血事件的严重程度主要为1级，且不需要进行干预治疗。严重出血在多吉美组与安慰剂组间的发生率相似。多吉美不会促进骨髓抑制的发生。观察到的低磷酸盐血症及脂肪酶活性增高的情况在多吉美组发生率稍高，但绝大多数病例均未因此中断或中止治疗。

临床疗效
多吉美用于治疗晚期肾癌患者，显示出重要的抗肿瘤活性。
II期随机终止试验(randomizeddiscontinuationtrial，RDT)结果显示：24周后无疾病进展的患者百分比，索拉非尼组和安慰剂组分别为50％和18％（p=0.0077）；随机分组后，索拉非尼组的平均无疾病进展生存期（PFS）（24周）明显长于安慰剂组（6周）（p=0.0087）。所有接受治疗的肾癌患者（202人）的总体生存期评价为29周。73名（36％）患者肿瘤缩小≥25％。
Ⅲ期肾癌治疗的全球性评价试验（treatmentapproachesinrenalcancerglobalevaluationtrial，TARGETs）结果表明，多吉美显著延长总体生存期（OS）2，3，与安慰剂相比使PFS延长1倍3。对PFS的疗效与性别、年龄、肿瘤纪念中心（MSKCC）风险分组、治疗史、ECOGPS评分的基线值、确诊后时间以及既往是否接受过细胞因子治疗无关。多吉美治疗可使84％的患者临床受益2，其中的大多数患者显示出了肿瘤缩小的证据。多吉美在发挥临床疗效的同时不影响总体健康相关生活质量（HRQOL）。与安慰剂相比，多吉美对肾癌特征性症状包括咳嗽、发热、“担心病情恶化”、呼吸急促、及“及享受生活的能力”亦可产生积极的影响。

Nexavar (Sorafenib)

Developed by Bayer Pharmaceuticals & Onyx Pharmaceuticals
The First Anti-Angiogenic Drug Approved for the
Treatment of Kidney Cancer
 
 
Nexavar is the First in a Highly Promising New Genre of Drugs Available for the Treatment of Kidney Cancer.

Nexavar Belongs to a New Class of Cancer Drugs, Referred to as Anti-Angiogenic Drugs or Angiogenesis Inhibitors.  The Anti-Cancer Agents Prevent The Metastasis of Cancer Cells and Enhance the Effectiveness of Chemotherapy.

The Newly-Authorized Drug Became the Second Angiogenesis Inhibitor Available for the Treatment  of Cancer.  (Avastin was the first anti-angiogenic drug to reach the market, receiving approval for the treatment of colorectal cancer in 2004).

Ongoing research trials are now evaluating Nexavar in the treatment of a broad range of cancers.  The cutting edge drug is now being assessed in the treatment of melanoma and lung, prostate and thyroid cancer.
 

New Alternatives for Kidney Cancer Treatment

Targeted Cancer Drugs Have Produced a Major Advance in the Treatment of Advanced Kidney Cancer.  Conventional Cancer Treatments Have Rarely Been Effective, Resulting In A Five-Year Survival Rate of Less Than 10 Percent. Kidney Cancer is Highly Resistant To Chemotherapy, and Only Five to 10 Percent of Patients have Responded to Interferon  Alfa, an Immune System Stimulant.

Six Targeted Drugs Are Now Available for the Treatment of Inoperable Kidney Cancer; Afinitor, Avastin, Nexavar, Sutent, Torisel and Votrient.

Clinical Research Trials Have Not Yet Determined Which Targeted Drug, or Combination of Drugs, is Most Effective in The Treatment of Advanced Kidney Cancer.

Ongoing Research Trials Are Comparing the Effectiveness of Newly-Approved Targeted Drugs.  Combinations of Targeted Drugs Also Are Under Evaluation.
Anti-Cancer Effects

Nexavar Belongs to a New Class of Cancer Drugs, Referred to As Anti-Angiogenic Drugs or Angiogenesis Inhibitors.  The Development of Anti-Angiogenic Drugs Ranks Among the Most Significant Recent Advances in Cancer Research And Treatment. 

Nexavar Became the Second Angiogenesis Inhibitor Available for the Treatment of Cancer. (Avastin was the First Anti-Angiogenic Drug to Reach the Market, Receiving Approval for the Treatment of Colorectal Cancer in 2004). 

Anti-Angiogenic Drugs Such As Nexavar Differ Radically from Conventional Cancer Treatments.  Unlike Chemotherapy and Radiation, Anti-Angiogenic Drugs Do Not Directly Induce the Death of Cancer Cells.  Instead, the Newly-Developed Drugs Halt the Process That Allows Cancer Cells to Metastasize.  

The New Class of Cancer Drugs Prevents the Formation of Blood Vessels, a Process Referred to as Angiogenesis.  Without the Development of New Blood Vessels, A Tumor Cannot Grow Beyond The Size of One to Two Millimeters in Diameter.

The development of angiogenesis allows tumors to receive the Oxygen and Nutrients Necessary for their continued growth. The Formation of new  Blood  Vessels also  Enables Cancer Cells to Escape into the Circulation.

Nexavar Inhibits the Production of Proteins that Stimulate Angiogenesis. The Anti-Cancer Agent Targets Vascular Endothelial Growth Factor Receptor (VEGFR) and Platelet-Derived Growth Factor Receptor (PDGFR).  Blocking these Receptors Restricts the Production of VEGF and PDGF, Thereby Limiting the Development of new Blood  Vessels.

Authorized Uses

Nexavar Was Approved for the Treatment of Advanced Renal Cell Carcinoma, The Most Frequently-Diagnosed form of Kidney Cancer, on December 20, 2005. 

The Targeted Drug Was Authorized For The Treatment of inoperable Heptocellular Carcinoma, The Most Common Form of Liver Cancer, on November 16, 2007.

Research Findings: Phase III Trial

An International Research Trial Demonstrated that Nexavar Delayed the Progression of Kidney Cancer, But Did Not Significantly Extend Survival.

The Food and Drug Administration approved Nexavar on the basis of an interim analysis, issued in January, 2005.  The analysis indicated  that treatment with Nexavar nearly doubled the time until cancer progressed.  The median progression-free survival was 5.5 months for patients treated with Nexavar, versus 2.8 months for patients who received a placebo.

A Subsequent Analysis, published in the New England Journal of Medicine on January 11, 2007, reported that Nexavar extended survival by almost four months. However, the increase in the Length of Survival was Not Considered Statistically Significant.

Research Findings indicated That the median overall survival of patients treated with Nexavar was 19.3 months. In Comparison, the Median Survival of Patients Who Received a Placebo was 15.9 Months.

Treatment with Nexavar also produced higher response rates. 

Nexavar produced complete remission in one patient, and partial remission in 10 Percent of patients.  Another 74 percent had no progression of cancer, referred to as stable disease. No patient who received a placebo entered complete remission, and  two percent developed partial remission.  Stable disease was reported in 53 percent.

Side Effects

Nexavar was generally well-tolerated by patients enrolled in the Phase III clinical trial.

Research findings, which were published in the New England Journal of Medicine in January, 2007, concluded that Nexavar produced "moderate and easily manageable toxic effects."

Severe Complications of Nexavar included Cardiac Ischemia and Myocardial Infarction.  In The Phase III Clinical Trial, Three Percent of Patients Suffered Cardiac Ischemia, The Disruption of Blood Flow To the Heart By The Blockage of a Coronary Artery,  or  Myocardial Infarction, A Severe Blockage That Results in a Heart Attack.

Trial Investigators Concluded that "the Overall Rate of These Events was Low, and the Risk-Benefit Ratio was Acceptable in the Context of an Apparent Clinical Benefit in Patients with a Fatal Disease."

The Most Common Side Effects Were Diarrhea, Rash, Fatigue, Hand-Foot Skin Reaction, Hair Loss and Nausea. Complications were Predominantly Classified as Grade 1 or 2, the Least Severe.
 

Research Study: Risk Of Hypertension

A Research Study Published in Lancet Oncology concluded that Nexavar significantly increased the risk of hypertension

The Study, Published in the February, 2008 Issue, Found that Patients Treated with Nexavar had Six Times the risk of developing hypertension. 

Research Findings Indicated that high Blood Pressure Developed  in 23.4 percent of Patients who received Nexavar.  High-grade Hypertension (classified as grade 3 or 4)  was Reported in 5.7 Percent of Patients.

The Research Study, Conducted by Investigators from the State University of New York  at Stony Brook, evaluated Data from Nine Clinical Trials. The Research Trials Evaluated Nexavar in the Treatment of Kidney, Liver and Prostate Cancer, as well as Melanoma.