A novel blood test identifies PAM4 (or clivatuzumab), an antigen that is present in almost 90% of pancreatic cancers and precancers.
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Patients with pancreatic cancer almost always have a poor prognosis, with a 5-year survival rate of only 2% to 3%, because the disease is rarely diagnosed at an early stage. However, researchers from the Garden State Cancer Center in Belleville, New Jersey, have developed a novel blood test for detecting early-stage pancreatic cancer that identifies and quantifies PAM4 (also called clivatuzumab), a unique antigen that is present in almost 90% of pancreatic cancers and precancers, but rarely in pancreatitis and never in the setting of a healthy pancreas or in other malignancies, such as breast, lung, and brain cancers. The research was presented by lead investigator David V. Gold, PhD, at the 2010 Gastrointestinal Cancers Symposium, and deemed to represent a significant clinical advance.
In 2006, Gold and colleagues had reported on the use of an enzyme immunoassay for quantitation of PAM4-antigen in the serum, which demonstrated a sensitivity for pancreatic cancer of 77% and specificity of 95%; however, the tumor size and disease stage of patients included in that analysis was unknown. The study reported at the 2010 Symposium, which included 19 healthy controls and 68 patients with pancreatic cancer who underwent surgical resection, showed the PAM4 serum immunoassay to correctly identify 13 of 21 stage I cancers (62%) and 12 of 14 stage II cancers (86%). When the stage I specimens were divided into stage IA (n = 13) and stage IB (n = 8) based on tumor size, the sensitivity rates were 54% and 75%, respectively. As anticipated, the test had a high sensitivity for detecting stage III/IV, correctly identifying 30 of 33 cases (91%). The test had incorrectly identified one normal tissue specimen as cancer.
Tumor specimens had a median serum PAM4 level of 9.85 U/mL, ranging from 4.53 U/mL for stage I disease to 13.37 U/mL for stage III/IV disease, whereas noncancerous specimens had a median serum value of 1.18 U/mL. According to Gold, “In this study, we found that the PAM4 protein is quite accurate at identifying patients with pancreatic cancer and, if validated in larger studies, would be a promising tool for detecting this disease in its earlier, more treatable stages, before it spreads to other organs.” Currently, only 7% of pancreatic cancer cases are detected before they have metastasized.
Building on the findings of this study, Gold and colleagues conducted a separate assessment to determine whether PAM4-based targeting of therapeutic materials (radioisotopes, drugs, toxins) that are linked to the antibody may improve outcomes when used to treat patients with early-stage pancreatic cancer. The initial findings of the study, which included 21 patients, appear promising, demonstrating an almost 70% response rate, with partial responses observed in 23% of patients and stable disease in 45%. In addition, treatment was generally well tolerated, with few nonhematologic adverse events. Patients also reported good performance and decreased pain medication requirements during treatment.
According to Robert P. Sticca, MD, chairman, Department of Surgery, and professor, University of North Dakota School of Medicine and Health Sciences, who moderated the session, this study of PAM4 is especially exciting because, in addition to potentially allowing for the early diagnosis of pancreatic cancer, “it has the additional added benefit of a possibility for treatment options.”
Gold DV, Goggins M, Newsome G, et al. The PAM4 serum enzyme immunoassay for detection of early-stage pancreatic carcinoma. Abstract 135. Presented at: 2010 Gastrointestinal Cancers Symposium. January 22-24, 2010; Orlando, Florida.
Pennington KL, Guarino MJ, Sheikh A, et al. Repeated treatment cycles of fractionated radioimmunotherapy combined with low-dose radiosensitizing gemcitabine in advanced pancreatic cancer. Abstract 247. Presented at: 2010 Gastrointestinal Cancers Symposium. January 22-24, 2010; Orlando, Florida.