胰脏癌治疗疫苗显示有效

　　January 22, 2007 (奥兰多) — 一个实验中的胰脏癌治疗疫苗显示，在切除后与放射线和化疗并用可以提高存活；Cell Genesys 公司的新产品GVAX第2期研究之最新结果是基于平均3年的追踪期，显示平均整体存活有26个月。
　　
　　药厂指出，和过去其他研究所发表的17到22个月的平均存活资料相比，这个结果更为人接受。
　　
　　Emory大学医学院的Charles Staley医师表示，身为一个胰脏外科医师，当看到以手术并用放射线化疗的最佳存活率只有18到19个月时，是令人沮丧的，在胰脏癌治疗方面，我们仍在起步阶段，所以这个可以存活26个月的报告还不错 ，但他强调这是第2期研究的结果，需要第3期的研究来得到更好的概念。
　　
　　Staley医师是美国临床肿瘤学会2007年胃肠道癌症研讨会(GCS)的记者会主持人，第2期试验的研究结果在会议中由John Hopkins Kimmel 癌症中心的Daniel Laheru医师发表，目前已在计划第3期研究。
　　
　　Laheru医师指出，第3期试验中也以同样的免疫治疗方法探究对前列腺癌的效果。
　　
　　【单一机构研究】
　　Laheru医师解释，这种治疗方式的概念是在不损及免疫系统下，让免疫系统重新认知胰脏癌细胞是外来物，此疫苗是由胰脏癌细胞萃取而得，用放射线处理后以基因工程使其分泌“粒细胞巨噬细胞集落刺激因子(GM-CSF) ”，这个观念是GM-CSF吸引免疫细胞到注射部位，即胰脏癌细胞抗原处，之后这些成分可以在身体内四处巡逻，并摧毁有相同抗原的细胞。
　　
　　第2期试验是一个含有60位扩散到胰脏外可手术之胰脏腺癌病患的单一机构研究，所有病患在手术后第8到10个月接受第一剂疫苗，接着进行 5-flurouracil 化疗和放射线治疗。
　　
　　化疗和放射线治疗后1个月无发病的病患，则以每一个月的间隔接受3剂追加疫苗，接着在6个月后追加第5剂。
　　
　　目前的结果显示1年存活率为 88%，2年存活率是76%；Laheru医师指出，相关研究的历史资料显示，仅以手术治疗的病患一年平均存活率为63% ，2年存活率是42%，他的团队现在比较各个手术后并用化疗和放射线治疗的相关资料结果，初步结果认为该疫苗可以提供化疗和放射线治疗以外的附加效果。
　　
　　Laheru医师指出，需要进行前溯式随机试验以确定此一发现，我们现在计划一个第3期研究以检验最佳的手术并用或不并用该疫苗的治疗方式。
　　
　　Laheru医师指出，疫苗的副作用仅限于注射部位的局部反应，包括痒和红肿，一般在注射后第7到10天消失。
　　
　　同一产品的稍早的研究包括14位病患，包含该疫苗的数个不同剂量 (Jaffee EM 等人. J Clin Oncol. 2001;19:145-156)；该试验中，8 位病患有3位接受治疗剂量，之后维持无病存活至少8年；Cell Genesys 公司在声明中指出，这个结果相当显著，因为这3个长期存活者原本手术后的显微镜检显示有残留胰脏肿瘤且有淋巴结转移，而被认为是有高复发风险者；此外，这3个长期无病存活的病患显示有治疗相关的抗肿瘤免疫力，包括诱导 T-细胞反应到肿瘤相关的抗原mesothelin。
　　
　　2007 GCS:摘要106. 发表于 January 20, 2007.

Therapeutic Vaccine for Pancreatic Cancer Shows Promise

By Zosia Chustecka
Medscape Medical News

January 22, 2007 (Orlando) ??An experimental therapeutic vaccine for pancreatic cancer appears to boost survival when added to adjuvant radiation and chemotherapy following resection. The updated results from a phase 2 study of the product, GVAX, developed by Cell Genesys Inc, are based on a median follow-up of 3 years and show a median overall survival of 26 months.

This compares favorably with historical published data, which show a median survival of between 17and 22 months, say the manufacturers.

"As a pancreatic surgeon, it's been very frustrating to watch these outcomes ??survival rates of 18 to 19 months are the best that we can achieve with surgery and adjuvant chemoradiation," commented Charles Staley, MD, from Emory University School of Medicine, in Atlanta, Georgia. "We've been taking baby steps in pancreatic cancer," he continued, so this report of survival to 26 months is "not bad." However, he emphasized that the result comes from a phase 2 study, and "we need a phase 3 study to get a better idea."

Dr. Staley was moderating a press briefing organized by the American Society of Clinical Oncology here at the 2007 Gastrointestinal Cancers Symposium (GCS). Results from the phase 2 study were presented at the meeting by Daniel Laheru, MD, from the John Hopkins Kimmel Cancer Center, in Baltimore, Maryland. He said a phase 3 study is now planned.

Dr. Laheru noted that a similar immunotherapy approach was currently being explored in a phase 3 trial in prostate cancer.

Single-Institution Study

The idea behind this approach to treatment is that the "immune system is intact but needs to be retrained to recognize pancreatic cancer cells as foreign," Dr. Laheru explained. The vaccine is made from cells extracted from pancreatic cancers, irradiated and then genetically engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). The idea is that the GM-CSF attracts immune cells to the injection site, where they are exposed to pancreatic cancer antigens, and then they patrol around the body destroying cells with the same antigen profile.

The phase 2 trial was a single-institution study involving 60 patients with operable pancreatic adenocarcinoma already spread beyond the pancreas. All patients received their first vaccine at 8 to 10 months after surgery, followed by 5-flurouracil chemotherapy integrated with radiation.

Patients who were disease-free 1 month after chemoradiation received 3 additional vaccine doses 1 month apart, followed by a fifth booster vaccine 6 months later.

The updated results show a 1-year survival rate of 88% and 2-year survival rate of 76%. Dr. Laheru noted that historical data from studies in which patients were treated with surgery alone show average survival rates of 63% after 1 year and 42% after 2 years. His team is now comparing the results with another database in which patients received adjuvant chemoradiation after surgery, and "our initial review suggests that the vaccine could provide additional benefit over chemoradiation."

Dr. Laheru noted that prospective randomized trials are needed to confirm this observation. "We are now planning a phase 3 study to test the best surgical and the best adjuvant approach together, with and without the addition of the vaccine."

Vaccine side effects were limited to local reactions at the injection site, including itching, redness, and swelling, and typically disappeared after 7 to 10 days, Dr. Laheru noted.

An earlier study of the same product, conducted in 14 patients, explored several different doses of the vaccine (Jaffee EM et al. J Clin Oncol. 2001;19:145-156). In that trial, 3 of 8 patients who received therapeutic-dose levels of the vaccine had disease-free survival for at least 8 years. "This outcome is considered particularly significant, since all 3 long-term survivors were judged to be at high risk for recurrent cancer due to microscopic evidence of residual pancreatic tumor following surgery and/or metastatic tumor in regional lymph nodes," Cell Genesys notes in a statement. "In addition, the 3 patients with prolonged disease-free survival ??but not the 5 who progressed and died ??showed evidence of treatment-associated antitumor immunity, including induction of T-cell responses to the candidate tumor-associated antigen mesothelin."

2007 GCS: Abstract 106. Presented January 20, 2007.