辉瑞公司宣布，Sutent在治疗晚期胰腺内分泌肿瘤的III期临床实验中达到了主要临床终点，即患者在病情无恶化的情况下生存期得以延长。目前，用于治疗这种疾病的药物极为稀少，在这一领域进行开发对辉瑞来说具有非凡的战略意义。

此前，Sutent在治疗该症的II期临床实验中也获得了成功，这是它后来能顺利进入III期临床的重要基础，两次实验的受试者为同一批人员，为66名晚期胰腺内分泌肿瘤患者。他们使用Sutent进行治疗后应答率为16.7%，达到预定目标，68%的患者病情可保持稳定，体内肿瘤出现恶化的平均时间为7.7个月，而其中81.1%的患者生存期能达到1年。

胰腺内分泌肿瘤是一种罕见的疾病，每年在美国发现的病例仅为2500例。虽然与胰腺癌相比较，胰腺内分泌肿瘤的预后更好，但晚期患者一旦不能通过手术治疗，他们所能选择的有效药物近乎没有，因此市场上对这类产品的需求异常强烈。

Sutent是一种多靶点酪氨酸激酶抑制剂，已在美国、欧盟和日本等国家和地区获准治疗晚期肾细胞癌和胃肠道间质瘤，因为上市后销量迅速增加而已在医学界被人熟知。

Sutent (Sunitinib)

Developed by Pfizer
 
One of Six Anti-Angiogenic Drugs Now Available For The Treatment of Kidney Cancer

Advanced Kidney Cancer, Which Rarely Responds To Chemotherapy Or Biologic Drugs, May Now Be Treated With The Targeted Drug Sutent.

Sutent Belongs To A Revolutionary New Class of Cancer Drugs, Referred To As Angiogenesis Inhibitors or Anti-Angiogenic Drugs. The Anti-Cancer Agents Are The First That Do Not Directly Induce The Death Of Cancer Cells.  Instead, Anti-Angiogenic Drugs Prevent The Development of Blood Vessels That Allow Cancer Cells To Metastacize.

The New Genre of Cancer Drugs Has Proven To Be Most Effective In The Treatment of Kidney and Ovarian Cancer In Clinical Trials.  Both Cancers Produce High Levels of VEGF (Vascular Endothelial Growth Factor), A Critical Protein Targeted By Anti-Angiogenic Drugs.

Sutent And Five Other Targeted Drugs Have Produced A Significant Advance In The Treatment For Inoperable Kidney Cancer.  Biologic Drugs Have Proven Highly Ineffective, Resulting In A Five-Year Survival Rate of Less Than 10 Percent. Interferon Alfa, An Immune System Stimulant That Was Previously the Standard Treatment For Advanced Kidney Cancer,  Produced Clinical Responses In Only Five to 10 Percent of Patients.

Sutent and Other Targeted Drugs Cannot Be Considered A Cure For Metastatic Kidney Cancer, But Have Dramatically Improved Clinical Responses. An International Research Trial Found That Sutent Significantly Increased Response Rates, With Approximately One-Thirdof Patients Entering Complete Or Partial Remission.  The Newly-Authorized Drug Also Delayed The Progression of Kidney Cancer Twice As Long As Interferon Alfa.

National Cancer Institute-Sponsored Research Trials Are Now Continuing To Evaluate Sutent In The Treatment of Inoperable Kidney Cancer. Research Findings Will Determine Which Targeted Drug, Or Combination  of Drugs, Is Most Effective In The Treatment of Advanced Kidney Cancer.

Ongoing Clinical Trials Are Comparing The Effectiveness of Sutent With Four Other Targeted Kidney Cancer Drugs:   Afinitor, Nexavar, Torisel and Votrient.

Sutent Also Is Under Investigation In Combination With Other Newly-Authorized Drugs.  Research Trials Are Assessing Sutent In Combination With Avastin And Torisel.

Anti-Cancer Effects

The Development of Anti-Angiogenic Drugs Such As Sutent Ranks Among the Most Significant Recent Advances in Cancer Research And Treatment. 

Anti-Angiogenic Drugs Differ Radically From Conventional Cancer Treatments.  Unlike Chemotherapy and Radiation, The Anti-Cancer Agents Do Not Directly Induce the Death of Malignant Cells.  Instead, Anti-Angiogenic Drugs Prevent The Metastasis of Cancer Cells.

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.

Sutent Inhibits the Production of Proteins thatStimulateTheProcessofAngiogenesis. 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. 

Sutent Also Targets the VHL Gene, which Plays a Critical Role in the Development of Angiogenesis.  Laboratory Research has Indicated That The VHL Gene is Inactivated in An Estimated 80 Percent of Cases of Non-hereditary Kidney Cancer. Functional VHL Genes Act to Suppress the Development of Tumors.

The VHL Gene Regulates the Production of Proteins that Stimulate Angiogenesis.  Elevated Levels of These Proteins, VEGF and PDGF, are Associated with Tumor Growth and Metastasis.
 
FDA Approval

Sutent Received Accelerated Approval For the Treatment of Advanced Renal Cell Carcinoma, The Most Frequently-Diagnosed form of Kidney Cancer, In January, 2006.

The Targeted Drug Also Received Approval For the Secondary Treatment of Gastrointestinal Stromal Tumors (GIST), in January, 2006.
 
Research Findings: Phase III Trial

An International Research Trial Confirmed that Sutent was Superior to Interferon Alfa, the Standard Treatment for Inoperable Kidney Cancer.

Findings of the International Trial, Published in the New England Journal of Medicine on  January 11, 2007,  concluded that Sutent Delayed the Growth of Cancer Significantly Longer than  Interferon Alfa, An Immune System Stimulant.

Sutent Delayed the Progression of Cancer More than Twice as Long as Interferon Alfa. The Median Progression-Free Survival for Patients Treated with Sutent was 11 Months, Compared to Five Months for Patients who Received Interferon Alfa.

Response Rates also were Substantially Increased in Patients who received Sutent. Complete or Partial Remission Developed in 31 Percent of Patients treated with Sutent. In Comparison, only 6 Percent of Patients who were given Interferon Alfa entered Remission.

The Phase III Clinical Trial, Which was Conducted in Australia, Brazil Canada, Europe and the United States, Enrolled 750 Patients who had received No Prior Drug Therapy.  Sutent was Administered to 375 Patients, and Interferon Alfa was Given to the Remaining 375 Patients. The Treatment  Groups Were Comparable in Demographic and Disease Characteristics.

Quality of Life & Side Effects

The Phase III Research Trial Concluded that Patients Treated with Sutent had significantly Better health-Related Quality of Life than Patients who Received Interferon Alfa.

Quality of Life Was Assessed in Two Separate Questionnaires Completed by Patients Enrolled in the International Clinical Trial. Research Findings, Published in the New England Journal of Medicine in January, 2007, Concluded That "Higher Scores (indicating Better Quality of Life in the (Sutent) Group for Kidney Cancer-Related Symptoms and Overall Quality of Life Were Clinically Meaningful on the Basis of Established Guidelines."

The Incidence of Severe Side Effects Was Comparable Between Patients Treated with Sutent and Those Who Received Interferon Alfa.
A Research Analysis reported that  "the Proportion of Patients with Grade Three or Four Adverse Events Was Relatively Low in Both Groups."

Treatment-Related Fatigue Developed Less Frequently in Patients Who Received Sutent.  Fatigue was Reported in Seven Percent of the Sutent Group, Compared to 12 Percent in the Interferon Alfa Group.

Other Side Effects were More Common in Kidney Cancer Patients Treated with Sutent. These Adverse Effects were Characteristically Reversible with a Dose Modification or the Discontinuation of Treatment.

Treatment with Sutent Produced Higher Rates of Hypertension (Eight Percent, compared to One Percent of Patients Treated with Interferon Alfa); Diarrhea (Five Percent versus No Cases); Vomiting (Four Percent Compared to One Percent); and Hand-Foot Syndrome (Five Percent versus No Cases).

Research Study: Risk Of Hypertension

A Research Study Published in Lancet Oncology found that Treatment with Sutent carries an Increased Risk of Heart Failure and Hypertension.

The Study Advised that Patients treated with Sutent, Especially Those with Coronary Artery Disease or Other Cardiac Risk Factors, be Monitored for Cardiovascular Side Effects.

Research Findings, Published in the December 15 2007, Issue, were Based on Patients who were treated with Sutent for Gastrointestinal Stromal Tumors (GIST),

The Research Analysis Evaluated the Records of 75 patients Enrolled in a Phase  I and II Clinical Trial at the Dana-Farber Cancer Institute.

Cardiovascular Side Effects Developed in 11 percent of Patients Enrolled in the Research Trial. Two Patients Suffered Heart Attacks, and Six Other Patients Had Heart Failure.

Hypertension was Reported in 47 percent of Patients, and 20 percent of Patients had reduced Heart Function.

The Incidence of Cardiovascular Side Effects was Highest in Patients with a History of Coronary Artery Disease and Hypertension.

Cardiovascular complications were generally manageable, and most patients who suffered heart failure were able to resume treatment with Sutent.