疫苗治療可能對多型性神經膠母細胞瘤有效


  April 26, 2006 (舊金山) — 研究團隊於2006年美國神經外科醫師學會年會時發表指出,多型性神經膠母細胞瘤病患全切除手術和標準治療之後,以一胜肽疫苗治療,可以達到平均存活18個月以上。
  
  儘管最近併用temozolomide (Temodar)化療和切除手術和放射線治療,神經膠母細胞瘤病患平均存活率仍僅14個月左右;然而,研究團隊知道有將近30%到50%的神經膠母細胞瘤癌細胞的上皮細胞生長因子接受器(EGFRvIII)有各種不同表現,且僅出現在癌細胞上,因此這些受體適合作為疫苗的目標區。
  
  進行中的第2期臨床試驗中,有23位初診斷為神經膠母細胞瘤的病患被隨機分組接受兩種免疫處方之一;第一種處方中,每月追加注射之後,病患每兩週接受3次的胜肽疫苗(PEPvIII-KLH)加一劑的免疫活化劑顆粒球巨嗜細胞聚落刺激因子(GM-CSF);第二種處方中,每月追加注射之後,病患每兩週接受3劑的GM-CSF加生理食鹽水。
  
  所有病患皆進行全切除手術,在免疫治療開始之前,先併用temozolomide和放射線治療;病患在休士頓德州大學安德森癌症中心,和北卡羅來納州杜克大學醫學中心接受治療。
  
  德州大學安德森癌症中心神經外科助理教授Amy B. Heimberger醫師發表時指出,病患平均病程為12.1個月,相較於歷史對照控制組的7.1個月較為人所接受;比較去年發表在新英格蘭醫學期刊上temozolomide第3期臨床試驗,平均病程為6.9個月。
  
  Heimberger醫師表示,雖然迄今還沒有對研究中的所有病患平均整體存活率作分析,但目前已知可以達18個月以上;前述的temozolomide第3期臨床試驗中,平均整體存活率為14.6個月。
  
  病患接受疫苗治療之後復發取得之腫瘤樣本,不再表現有EGFR 變異蛋白質,因此認為腫瘤可以逃過疫苗引發的抗體;疫苗看來是安全的,且不會誘發自體免疫;所有的病患有等級1的注射位置反應,有一位病患出現有可能的等級1過敏反應且因此從研究中退出。
  
  此研究的共同負責人John Sampson醫師向Medscape表示,他和他的同事以及授權生產該疫苗的Celldex Therapeutics (Phillipsburg, NJ)計畫進行一個第二次的多中心第二期臨床試驗;將測試該疫苗和現行的temozolomide治療併用。
  
  因為temozolomide有某些免疫抑制效果,如此併用或可證明疑義;然而,Sampson醫師表示,在動物實驗的模式提供給藥時間的相關時間建議,可以使得他們對疫苗的有效性上獲得助益。
  
  麻州綜合醫院神經外科主治醫師Robert L. Martuza討論此研究時表示,大於18個月的平均存活率是卓越的,但是對於神經膠母細胞瘤的免疫治療而言,還有許多新的挑戰;目前的類固醇免疫抑制劑量被用來控制病患的水腫,若此疫苗或者其他類似治療可以奏效,臨床研究者將可以有更多的方法應付此問題;他指出,對神經外科醫師而言這是一個有助於解決問題的挑戰。

Vaccine Therapy Appears Promis

By
Medscape Medical News

April 26, 2006 (San Francisco) — Glioblastoma multiforme patients treated with a peptide vaccine after gross total resection and standard therapy have a median survival beyond 18 months, researchers reported here at the 2006 annual meeting of the American Association of Neurological Surgeons.

Despite the recent addition of temozolomide (Temodar) chemotherapy to the combination of resection and radiation, median survival for patients with glioblastoma remains around 14 months. Researchers know, however, that approximately 30% to 50% of glioblastoma tumors express a variant of the epidermal growth factor receptor (EGFRvIII), which is found only on cancer cells, and thus this variant receptor may make a good vaccine target.

In the current phase 2 study, 23 patients with newly diagnosed glioblastoma were randomized to receive 1 of 2 immunization regimens. In the first regimen, patients received 3 doses of the peptide vaccine (PEPvIII-KLH) plus the immune stimulant granulocyte-macrophage colony-stimulating factor (GM-CSF) every 2 weeks followed by monthly booster shots. In the second regimen, patients received 3 doses of GM-CSF plus saline every 2 weeks followed by monthly booster shots of the complete vaccine.

All patients were treated with gross-total resection, adjuvant temozolomide, and radiation prior to starting the immune therapy regimen. Patients were treated at the University of Texas MD Anderson Cancer Center in Houston or at Duke University Medical Center in Durham, North Carolina.

“The median time to progression in patients was 12.1 months, which compares favorably to the 7.1 months in a group of matched historical controls,” said Amy B. Heimberger, MD, an assistant professor of neurosurgery at the University of Texas MD Anderson Cancer Center in Houston, who presented the work. By comparison, median time to progression was 6.9 months in the phase 3 trial of temozolomide, as reported last year in the New England Journal of Medicine.

Although median overall survival has not yet been reached in the patients being studied, it is already beyond 18 months, said Dr. Heimberger. Again, that compares favorably to the 14.6-month median survival for patients who participated in the phase 3 temozolomide study.

Tumor samples from patients who relapsed after vaccine therapy no longer express the EGFR variant protein, thereby suggesting that the tumors are able to escape the vaccine-induced antibodies. The vaccine appeared safe and did not appear to induce autoimmunity. All patients had grade I injection site reactions and 1 patient had a possible grade I allergic reaction and was withdrawn from the study.

John Sampson, MD, PhD, coprincipal investigator on the study, told Medscape that he and his colleagues, along with Celldex Therapeutics (Phillipsburg, NJ), which has licensed rights to the vaccine, are planning a second multicenter phase 2 trial. That trial will test the vaccine with concurrent ongoing temozolomide therapy.

Because temozolomide has some immunosuppressive effects, the combination may prove challenging. However, Dr. Sampson said that work done in animal models suggests that the relative timing of the administration of the drug could be made to work to their advantage and increase the vaccine’s effectiveness.

The greater-than 18 month median survival is remarkable, but working with an immunotherapy for glioblastoma will bring about new challenges, said Robert L. Martuza, MD, chief of the neurosurgical service at Massachusetts General Hospital in Boston, who discussed the study. Currently immunosuppressive doses of steroids are used to control edema in these patients. If this vaccine therapy or others like it are to work, clinical researchers will have to find another way to address the problem. “This is a challenge that neurosurgeons can help address,” he said.

AANS 2006 Annual Meeting: Abstracts 703. Presented April 25, 2006.

Reviewed by Marni Kelman, MSc

    
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