The increasing incidence of pancreatic cancer, expected to cause 20,000 deaths a year by 1975, making it the fourth-leading cancer killer, has elevated this cancer site into the major league. James A. Peters, director of NCI’s Division of Cancer Cause & Prevention, conveyed this information to the National Cancer Advisory Board.
Cancer of the pancreas has thus gained a spot in the national cancer program as a major priority for concentrated, sharply targeted action. A significant increase in research activity may be expected during the next year, as emphasized by Peters and others in their presentations to the Board.
Extremely low survival rates, difficulty in early diagnosis, and a lack of response to treatment and surgery characterize the disease. But a growing number of clues indicate it is an “essentially man-made disease and therefore, by definition, a preventable one,” Peters said.
“The profile of the individual at high risk for cancer of the pancreas is that of a heavy smoker on a western diet high in cholesterol and fat. Other minor factors may include city living, race, a family history of multiple polyposis, and the ataxiatelangiectasia syndrome,” Peters said.
“Desirable and feasible research,” Peters said, is needed and includes:
- Consideration of anatomical characteristics of the tumor, whether it originates in acinar or duct cells. Acinar origin would lend credibility to endogenous etiologic theories, perhaps incriminating viruses, while a duct cell origin would be more consistent with carcinogenic origination outside of the pancreas itself.
- General location of the cancer in the pancreas.
- Close scrutiny of the biochemistry and fate of biliary acids.
- Chemical configuration of bile acids and determination of how smoking, high cholesterol, and fat consumption affect bile composition, perhaps adding to its carcinogenic load. The role of betanaphthylamine should also be investigated since chemists exposed to this compound have shown a higher risk of pancreatic cancer.
Research opportunities in etiology and prevention listed by Peters were:
- Epidemiology: Environmental and host-related factors, prospective studies of high-risk groups.
- Tumor biology: Morphology, biochemistry, physiological, and metabolic conditions.
- Development of experimental models: Total models of metabolic and physiological characteristics similar to man; organ and cell cultures; partial models for carcinogen bioassay.
- Testing of etiologic hypotheses: Bile reflux, liver metabolism, bile acids, dietary etiology, nitrosamines, B-naphthylamine, other diet carcinogens; viral etiology.
Diagnosis research opportunities listed were:
- Prospective studies of high-risk groups to discover early symptoms or disease markers, predisposing conditions.
- Tumor biology: Biochemical markers, proteins, t-RNA, enzymes; immunological markers, EA virus antigens.
Therapy research opportunities listed were:
- Tumor biology, to identify characteristics amenable to optimum therapy.
- Clinical trials, chemotherapy.
- Surgical management.
- Radiotherapy.
One of the big problems to be overcome to achieve significant progress is the development of a suitable animal model. “If the reflux theory is as significant as it appears to be,” Peters said, “then experimental models must be physiologically close to the human situation.” Small animals are not suitable, and even the does not provide biliary composition and metabolism relevant to man.
Some primates may be acceptable, although adding complications to research logistics. Smaller animals may be used as partial models.
Joseph F. Fraumeni, associate chief of epidemiology, discussed epidemiologic considerations:
- Incidence and mortality from pancreatic cancer in the U.S. have risen more rapidly in blacks than whites.
- It is relatively rare in Japan, but Japanese migrating to the U.S. reach a risk close to prevailing rates here.
- The highest rate in the world is reported for the Maoris of New Zealand. Hawaiians, also a Polynesian group, have rates nearly as high. American Indian females have rates significantly higher than whites.
- Diabetics have a significantly increased risk.
- About 20% of patients dying with hereditary pancreatitis have pancreatic cancer at autopsy.
- No environmental exposure has been proven to cause pancreatic cancer. Only tobacco has been consistently implicated.
Stephen K. Carter, associate director for cancer therapy evaluation, pointed out that “survival rates are so poor … that aggressive therapeutic procedures are worthy of trial.”
The cure potential of surgery is limited, Carter said. Only 7 to 10% of patients undergoing surgery are alive after five years. There is hope that surgery plus radiation plus chemotherapy will work.
Clinical trials cited by Carter:
- Fluorouracil (15 studies, 212 patients), 60 responses.
- Streptozotocin (2 studies, 18 patients), 7 responses.
- Mitomycin C (4 studies, 44 patients), 12 responses.
- Radiotherapy plus 5-fluorouracil. Radiotherapy plus 5FU: 32 patients, mean survival 10.4 months; radiotherapy plus placebo: 32 patients, mean survival 6.3 months.
- High dose (6,000R) plus 5-FU: 29 patients, 21% surviving after 30 months.
H. Marvin Pollard, Univ. of Michigan, reported on an American Cancer Society symposium on pancreatic cancer. “There is very little first-class research in the field,” Pollard quoted one symposium participant. Basic research needs include the effects of secretagogues on exocrine function, attention to the question of whether calcium is required or discharged in the secretory process, and the recovery of pancreatic cells from injury.
