An investigational immunoassay can accurately identify pancreatic cancer, potentially giving clinicians the ability to identify and treat the disease in its early stages, according to research that will be presented at the American Society of Clinical Oncology’s annual gastrointestinal cancer symposium.

The assay uses a monoclonal antibody to home in on malignant pancreatic cells; for added benefit, investigators are also employing the antibody to deliver targeted radiotherapy to tumor cells.

“We were able to identify the overwhelming majority of patients with early-stage disease,” lead author David V. Gold, Ph.D., said in a teleconference on Jan. 20 in advance of the meeting Jan. 22-24 in Orlando, Florida.

The PAM4 monoclonal antibody (clivatuzumab) quantifies blood levels of the PAM4 protein “that appears to be relatively unique to pancreatic cancer,” he said. The protein is not present in normal pancreatic tissue or in other types of malignancies. It also is rarely detected in pancreatitis, making it highly specific for pancreatic cancer.

In the small study, the researchers evaluated 68 patients who had undergone surgery for pancreatic cancer. The investigators obtained information about disease stage from surgical notes about the spread of the disease. They also evaluated 19 healthy controls.

The sensitivity of the PAM4 blood test for detecting stage I pancreatic cancer (disease confined to the pancreas), stage II disease (disease that has spread to nearby organs), and stage III/IV cancers (disease with local and distant spread) was 62%, 86%, and 91%, respectively. Overall, the assay was 81% sensitive for detecting all stages of pancreatic cancer.

“The PAM4 blood test is very specific for pancreatic cancer. If the assay is positive, there is a high positive diagnostic likelihood that the patient has pancreatic cancer,” said Dr. Gold, a researcher at the Garden State Cancer Center in Belleville, New Jersey.

If validated, the assay would be valuable for the management of patients with the disease. Most patients do not have symptoms until the advanced stages of tumor growth, when cure is unlikely. Currently, only an estimated 5% of patients with pancreatic cancer survive to 5 years, according to the American Cancer Society.

The PAM4 antibody has the potential to be part of an effective therapy as well. “Detection of the PAM4 antigen in the blood of these patients means that the cancer is producing the protein, and that this protein may act as a marker on the tumor for use of the antibody to target drugs and/or radioisotopes directly to the tumor,” said Dr. Gold.

Researchers have already begun to explore attaching radioisotopes to the antibody in order to image tumors, or to target radiotherapy of the tumor cells in combination with chemotherapy. In a small related study, the researchers achieved a partial response rate (defined as at least a 30% reduction in the size of the tumor) of 23% and a stable disease rate of 45% in patients with stage III and IV pancreatic cancer.

“By using the combination of early detection and therapy improvements, we hope to be able to come up with a new paradigm for the management of the patient with pancreatic cancer,” Dr. Gold said.

The assay still needs to be validated in larger trials, however. He estimated that the assay and related therapies are still 2-3 years from clinical use.

Senior author Dr. David Goldenberg disclosed that he is the chief scientific officer and chairman of the board of directors for Immunomedics Inc., a biopharmaceutical company that develops monoclonal, antibody-based products for the targeted treatment of cancer and other diseases.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

根据一项将在美国临床肿瘤学会胃肠癌研讨会上报告的研究，一种试验性免疫检测方法可准确检出胰腺癌，这可能使临床医生便于早期发现并治疗该病。

 

该检测方法采用一种单克隆抗体来追踪恶性胰腺细胞；目前研究者还采用这种抗体来使放疗靶向于肿瘤细胞，这是采用单克隆抗体的另一个益处。

 

上述年会将于1月22~24日在佛罗里达州奥兰多举行。在1月20日提前举行的电话会议上，第一作者David V. Gold博士说道：“我们能够检测出绝大多数早期疾病患者。”

 

他表示，PAM4单克隆抗体(clivatuzumab)可量化血液中的PAM4蛋白水平。PAM4蛋白“是胰腺癌相对特有的一种蛋白” ，其不存在于正常胰腺组织和其他类型恶性肿瘤中。在胰腺炎患者中也较少检测到这种蛋白，因此它对胰腺癌具有高度特异性。

 

在这项小规模研究中，研究者评价了68例接受胰腺癌手术的患者。研究者从记录癌扩散情况的手术记录中收集有关癌症分期的资料。他们还评价了19例健康对照者。

 

PAM4血检法在检测胰腺癌I期(癌细胞仅局限于胰腺)、II期(癌细胞扩散至邻近器官)和III/IV期(局部和远端扩散)方面的敏感性分别为62%、86%和91%。总体而言，该检测方法在检测所有分期胰腺癌方面的敏感性为81%。

 

新泽西州贝尔维尔花园州癌症中心的Gold博士说：“PAM4血检法对胰腺癌具有高度特异性。如果检测结果为阳性，那么诊断胰腺癌的可能性就较高。”

 

如果通过验证，那么该检测方法对于该病患者的治疗将具有重要意义。多数患者直到癌症晚期才出现症状，而此时要想治愈已不可能。根据美国癌症协会，目前的胰腺癌5年生存率仅约为5%。

 

PAM4抗体还可能成为有效治疗的一部分。Gold博士说：“在这些患者的血液中检出PAM4抗原，意味着胰腺癌细胞正在生成这种蛋白。在应用PAM4抗体使药物和或放射性同位素直接靶向于胰腺癌细胞时，这种蛋白可作为胰腺癌标志物。”

 

研究者已开始探索将放射性同位素附着于该抗体上，对肿瘤进行显像，或使放疗靶向于肿瘤细胞，增强放化疗联合治疗的效果。在一项小规模相关研究中，III期和IV期胰腺癌患者中的23%获得部分缓解(定义为肿瘤体积至少缩小30%)，45%病情稳定。

 

Gold博士说：“我们希望借助早期检测及改善治疗，制订出一套新的胰腺癌治疗方案。”

 

但是，仍需要在更大规模试验中对该检测方法予以验证。他估计，该检测方法和相关治疗仍需2~3年才能应用于临床。

 

第一作者David Goldenberg博士披露自己是Immunomedics公司首席科学官和董事会主席。该公司是一家生物制药公司，致力于开发用于癌症与其他疾病靶向治疗的单克隆抗体产品。

 

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