Pancreatic Cancer

Pancreatic Cancer (PC)

Pancreatic cancer often presents with subtle early symptoms, leading to frequent misdiagnosis. As the disease progresses to advanced stages, symptoms become more severe and pronounced, making treatment significantly challenging with limited effectiveness.

Over the past 20 years, the diagnosis rate of pancreatic cancer in Taiwan has increased more than threefold, and the mortality rate has increased by 1.7 times. Each year, more than 2,500 new cases are reported, and pancreatic cancer ranked 7th among the top ten deadliest cancers in Taiwan in 2021, with a mortality rate of 11.3%. The five-year survival rate for unresectable pancreatic cancer is less than 5%.

According to the International Agency for Research on Cancer (IARC), in 2018, there were 451,000 global diagnoses of pancreatic cancer, resulting in 440,000 deaths. The 5-year survival rate for pancreatic cancer worldwide is less than 10%.

In the United States, as per the American Cancer Society (ACS) statistics in 2021, approximately 60,430 individuals were projected to be diagnosed with pancreatic cancer, leading to 48,220 deaths. Pancreatic cancer ranks as the 11th most common cancer in the US, but it holds the third position in terms of mortality, following lung and colorectal cancers. The 5-year survival rate for pancreatic cancer in the US is approximately 10% to 15%. In 2024, it is estimated that there will be 66,440 new diagnoses, with the number of deaths possibly reaching 51,750.

Causes of Pancreatic Cancer

Changes in DNA can potentially lead to cancer, and these changes may be inherited from your parents or may develop over time. The latter changes might be caused by exposure to harmful substances, but they can also occur purely by chance. To date, the exact causes of pancreatic cancer remain unclear. Approximately 10% of cases are considered familial or hereditary, while most pancreatic cancers occur randomly or are induced by factors such as smoking, obesity, and age.

If a direct relative of yours is diagnosed with pancreatic cancer, your own risk of developing the disease may also increase. Therefore, it is recommended that family members of pancreatic cancer patients undergo genetic mutation testing. Dr. Lin reminds us that having one family member with pancreatic cancer increases the relative risk by 4.5 times. If there are two family members, the risk increases to 6.4 times, and with three family members, the risk can be as high as 32 times. Additionally, the age of onset tends to be relatively younger, potentially under 50 years old (refer to the chinese news).

In addition, there are other factors that may increase an individual’s risk of developing pancreatic cancer:

Long-term diabetes
Chronic and hereditary pancreatitis
Smoking
Ethnicity
Age (over 60)
Gender (men have a slightly higher risk)
Regular consumption of red and processed meats
Obesity
The Risk (Potential Risk) of Long-Term Consumption of Sugary Beverages: Recently, a report highlighted the case of a woman in her 50s who discovered that her CA19-9 tumor marker level was over 40 times higher than the normal range during a blood test. After consulting with her doctor and making dietary adjustments, it was confirmed that her daily consumption of sweetened black tea was the cause of the abnormal marker. The woman had been drinking 1000 to 2000 mL of black tea every day for years, and after stopping, her CA19-9 levels quickly returned to normal. Ultrasound and other tests confirmed no presence of cancer cells. However, her doctor advised against the long-term consumption of sugary beverages to prevent the potential risk of pancreatitis or increased cancer risk.
Pancreatic cysts: Research indicates that approximately 10% of pancreatic cancer cases are associated with pancreatic cysts. The cysts most closely linked to malignancy are mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN). Regular MRI monitoring and early diagnosis by a physician are crucial. If the cysts present a high risk, surgical removal is often recommended to reduce the potential for future cancer development.

It is important to note that the presence of these risk factors does not guarantee that an individual will develop pancreatic cancer, nor does every person with pancreatic cancer necessarily have these risk factors. This information is intended for general health maintenance and reference.

Background of Pancreatic Cancer

Lack of effective treatment options: Treatment methods for pancreatic cancer include surgical resection, radiation therapy, and chemotherapy, but they all have certain limitations and challenges. Surgical resection is the preferred method for treating pancreatic cancer, but it can only be performed when the cancer is diagnosed early. Radiation therapy and chemotherapy can be used for advanced or metastatic pancreatic cancer, but their effectiveness is limited and can lead to side effects.

Difficult to Detect Early, High Mortality Rate: Due to the pancreas’ location behind the spine in the retroperitoneal space, pancreatic cancer often presents no symptoms in its early stages. Consequently, many patients are diagnosed at an advanced or terminal stage, making complete surgical removal challenging. Additionally, the malignant nature of pancreatic cancer cells, which are prone to metastasis and recurrence, contributes to its high mortality rate. Research indicates that the five-year survival rate for stage I pancreatic cancer can reach 90%, but it drops to just 13% by stage IV, highlighting the importance of early detection and treatment.

Notable individuals affected: Many well-known figures both domestically and internationally have succumbed to pancreatic cancer, including Steve Jobs, the co-founder of Apple Inc., French chef Paul Bocuse, and one of the “Three Tenors,” Luciano Pavarotti.

Diagnosis: Due to its location in the retroperitoneal cavity and its elongated glandular structure with both endocrine and exocrine functions, the pancreas is difficult to evaluate fully using ultrasound. Combined with the fact that pancreatic cancer often lacks obvious symptoms in its early stages and is surrounded by numerous blood vessels, once the cancer cells invade the surrounding vessels, it becomes inoperable.

High-Risk Groups: Risk factors for pancreatic cancer include high-sugar and high-fat diets, smoking, alcohol consumption, genetics, diabetes, obesity, and chronic pancreatitis. According to National Health Insurance data, type 2 diabetes ranks as the leading comorbidity associated with pancreatic cancer, indicating that diabetic patients should be particularly vigilant. Additionally, those who suddenly develop diabetes should be cautious, as this may be a sign of pancreatic cancer affecting insulin secretion and leading to elevated blood sugar levels.
- Dr. William Fisher has developed an algorithm to track how many newly diagnosed diabetes patients over the age of 50 will develop pancreatic cancer within three years. The diagnosis of diabetes not only correlates with an increased risk of pancreatic cancer, but the time interval between diabetes diagnosis and cancer development may also allow for early intervention. Additionally, this research aims to identify suitable biomarkers for better detection and treatment (original source).
Early symptoms to watch for: upper abdominal bloating, upper abdominal pain, weight loss (due to poor appetite, indigestion), changes in stool (oily, pale color, foul smell, difficulty flushing), diarrhea (persistent for several days), Jaundice (tea-colored urine, itchy skin, yellowing of the whites of the eyes), back pain, elevated blood sugar (more common in late-stage patients), and a recent diagnosis of diabetes last year.

Diagnosis of Pancreatic Cancer

To detect pancreatic cancer early, imaging examinations are still the more reliable method. Although serum tests (such as CEA and CA19-9 tumor markers) are not significant in the early stages and can only serve as a reference, they can still be chosen as one of the regular screening items.

Ultrasound

Ultrasound is a convenient diagnostic tool, but the presence of gas in the adjacent gastrointestinal tract can interfere and make it challenging to achieve comprehensive assessments of the pancreas.

Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)

Both imaging techniques have the drawback of sometimes being unable to identify tumors smaller than 2 centimeters, which accounts for about 1/3 to 1/4 of cases. Additionally, some patients may be allergic to contrast agents used in these procedures.

A research team led by Professor Wei-Chih Liao at National Taiwan University Hospital has developed an AI-assisted diagnostic system named “PPANCREASaver.” This system enhances the detection accuracy of pancreatic tumors smaller than 2 centimeters using CT imaging. In 2022, it received the Breakthrough Device designation from the U.S. FDA and has since been certified by the Taiwan Food and Drug Administration (TFDA). Currently, PPANCREASaver is available as a self-paid service at National Taiwan University Hospital.

Endoscopic Ultrasound

This method has the highest sensitivity for detecting tumors smaller than 1 centimeter, but it is an invasive procedure. The ultrasound probe must be passed through the intestinal wall to reach the pancreas, which carries some risks, making it a non-first-line diagnostic approach. However, compared to CT/MRI, which have high sensitivity and can simultaneously perform biopsy examinations, they are also more convenient.

Blood Tests – CEA and CA19-9 Tumor Markers

These blood tests can be used as risk indicators. However, elevated levels of these markers typically occur only in advanced-stage pancreatic cancer and can be affected by factors such as liver, kidney, and cystic diseases, leading to potential misinterpretations. Therefore, they can only serve as reference points.

Current Treatment Options for Pancreatic Cancer

Chemotherapy

Chemotherapy uses anticancer drugs to kill cancer cells, but the dense stromal tissue surrounding pancreatic cancer makes it difficult for the drugs to penetrate effectively, resulting in relatively lower efficacy. Chemotherapy often employs combination therapy to enhance effectiveness. For instance, a clinical study involving previously untreated metastatic pancreatic adenocarcinoma patients showed that the overall survival period for those receiving combination therapy with nab-paclitaxel + gemcitabine was 8.5 months, compared to 6.7 months for the gemcitabine-alone group. This combination therapy is considered less toxic than FOLFIRINOX and serves as a frontline chemotherapy option. However, chemotherapy may cause side effects such as nausea, vomiting, hair loss, and fatigue. It remains one of the main treatment modalities for pancreatic cancer.

Surgical Resection

When the size of the pancreatic tumor is smaller than 2 centimeters, more than 80% of patients are candidates for surgical treatment, significantly improving their prognosis. The practicality of surgery depends on tumor size, location, proximity to nearby blood vessels, and whether there is distant metastasis. However, only about 20% of newly diagnosed patients are deemed suitable for resection.

Current Treatment Reference Drugs

Due to the limited efficacy of current drugs and their limited impact on patient survival and quality of life, many researchers are seeking more effective medications and treatment methods.

Pancreatic cancer can be treated without chemotherapy. Some patients might opt out of chemotherapy due to its severe side effects or because their health condition is not suitable. Alternative treatments include surgery, radiation therapy, targeted therapy, and immunotherapy. Surgery can remove the tumor, radiation can shrink tumors or alleviate symptoms, and targeted and immunotherapy often have fewer side effects. Additionally, supportive therapies like pain management and nutritional support can improve quality of life. Patients should discuss with their doctors to decide the best treatment plan.

Onivyde® (Irinotecan Liposomal Injection)

Onivyde® is a nanoliposomal injection containing Irinotecan, a camptothecin derivative. Its mechanism of action is as a topoisomerase I inhibitor, a cytotoxic drug that has been approved and widely used for cancer treatment.
It is indicated for metastatic pancreatic cancer in combination with 5-fluorouracil and leucovorin for patients who have previously received gemcitabine.
Clinical trial data from 2016 revealed that using Onivyde® in combination therapy for advanced pancreatic cancer increased the one-year survival rate to 26%, a 63% improvement compared to the use of 5-fluorouracil/leucovorin alone.
Onivyde was included in Taiwan’s National Health Insurance coverage in 2018 and is also marketed in the United States, Europe, China, and Japan.
Potential side effects may include severe neutropenia, severe diarrhea, interstitial lung disease, and allergic reactions.

Gemzar® Injection (Gemcitabine HCl)

Gemzar® is an intravenous injection containing gemcitabine and is used in the treatment of non-small cell lung cancer, pancreatic cancer, bladder cancer, and other cancers. It is employed as a first-line treatment for inoperable stage II or III pancreatic cancer and metastatic stage IV pancreatic cancer. It can also be used in patients who have received prior treatment with 5-FU.
Its mechanism of action involves blocking DNA replication and cell division in cancer cells, thereby inhibiting their growth and spread. According to clinical trial reports, the overall median survival period with Gemzar® was 5.7 months, compared to 4.2 months for the control group treated with fluorouracil.
Potential side effects include nausea, vomiting, rash, and fever.

TS-1® Capsule (Tegafur、Gimeracil、Oteracil potassium Capsules)

S-1 is an oral capsule containing Tegafur, Gimeracil, and Oteracil potassium, with the main anticancer component being 5-FU. The primary mode of action of 5-FU is through competitive binding of its active metabolite FdUMP with dUMP and thymidylate synthase, simultaneously forming a trimer with reduced folate to inhibit DNA synthesis.
S-1 is mainly used to treat gastric cancer, pancreatic cancer, colorectal cancer, advanced non-small cell lung cancer, and biliary tract cancer. Common side effects include constipation, diarrhea, poor appetite, nausea, and vomiting. Clinical trial data showed that the median overall survival period for the S-1 monotherapy group was 9.66 months, similar to the Gemcitabine monotherapy group (8.80 months).
Patients receiving S-1 + Gemcitabine combination therapy had a median overall survival period of 10.05 months, longer than the Gemcitabine monotherapy group (8.80 months).

BIZENGRI® (zenocutuzumab-zbco)

In December 2024, the FDA granted accelerated approval for BIZENGRI® for the treatment of pancreatic cancer patients with Neuregulin 1 (NRG1) gene fusion mutations. Approximately 3% of pancreatic cancer patients exhibit this alteration, also known as NRG1 fusion positive.
Clinical trials conducted by Merus showed that 40% of the 30 pancreatic cancer patients with NRG1 gene fusion experienced tumor reduction. Among those who responded, two-thirds had their response last for at least six months.
The most common side effects include diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, difficulty breathing, rash, constipation, vomiting, abdominal pain, and edema.

>> Source: News Article

Investigational Drugs

SM-88 <Phase II/III>

SM-88 (tyrosine derivative [Td], mTOR inhibitor, CYP3a4 inducer, and oxidative stress catalyst) developed by Tyme Technologies is a targeted therapy with relatively low toxicity, leveraging the Warburg Effect along with oxidative stress to induce tumor cell death.
Its excellent suitability for pancreas cancer lies in its capacity to penetrate tumors and be well-tolerated by debilitated patients.
This drug development was terminated in 2021 due to the failure to meet the primary endpoint of overall survival in the Phase II/III clinical trial (NCT03512756).

EF-009 Wafer <Phase I> >>more

The mortality rate of pancreatic cancer (PC) is rising rapidly.
However, the treatment of pancreatic cancer remain a formidable challenge and has 5-year survival rate of approximately less than 5%. Surgery followed by adjuvant chemotherapy the standard of care – without additional therapy, over 90% of patients relapse and die. However, PC remains highly resistant to conventional chemotherapy.
The great challenges lies firstly, in delivering chemotherapeutic agents effectively to bypass the protective barriers around pancreatic cancer; and secondly, in reversing the immunosuppressive environment caused by the presence of cancer stem cells.
EF-009 Wafer developed by Everfront Biotech Inc. is a slow-releasing drug for the treatment of pancreatic cancer with multiple targeting effects. It can accumulate in targeted areas around the tumor, make it vulnerable and easily killed by chemotherapy or immune cells, with manageable toxicity.

More Investigational Drug Information

BIOGATE PRECISION MEDICINE: BGX targeted therapeutic biologic works by blocking intracellular signal transduction to inhibit cell proliferation and spread. In animal experimental studies, BGX has demonstrated significant effects in inhibiting tumor growth and metastasis, while extending survival rates. The company will soon apply for TFDA clinical trials (Chinese News)

Care and Considerations for Pancreatic Cancer Patients

Nutritional Support

Pancreatic cancer patients often experience malnutrition and weight loss. This may be due to blockage of the main pancreatic duct by cancer cells, leading to inadequate secretion of pancreatic fluid into the duodenum. Undigested fats are then excreted in the feces, resulting in steatorrhea, chronic diarrhea, and weight loss. Adequate nutritional support is essential, and it is recommended to supplement with a high intake of proteins while controlling fruit consumption.

Pancreatic Enzyme Supplementation

Patients with pancreatic cancer may be unable to secrete the enzymes necessary for digestion due to partial removal of the pancreas or pancreatic dysfunction. When the pancreas cannot produce enough enzymes to break down food, pancreatic enzyme supplements are needed. Discussing supplementation with a doctor or nutritionist can help improve the digestion and absorption of food.

If you experience poor digestion, a feeling of excessive gas in the abdomen, foul-smelling stools, floating stools with fat, abnormally colored stools, diarrhea, and weight loss, you should discuss taking digestive enzyme supplements with your doctor.

Pain Management

The pain and discomfort caused by pancreatic cancer are often due to chronic upper abdominal or back pain, which can worsen in the advanced stages of cancer, leading to “total pain.” Effective pain relief medication and other therapeutic measures are necessary to maintain a good quality of life. Patients should follow their physician’s instructions to alleviate the burden caused by pain. During hospitalization, the pain level for patients can reach as high as 10 (equivalent to labor pain), and the relief provided by oral or injectable pain medications may be limited. Consequently, patients can consider nerve block procedures as recommended by their doctor to significantly improve the impact of pain on their quality of life.

Psychological Support

The course of pancreatic cancer treatment may bring ongoing stress and anxiety to patients. They require continuous psychological support and care from family and friends. If needed, patients can seek the assistance of psychologists, mental health professionals, or even spiritual care providers to maintain a positive psychological state.

In the terminal stage of pancreatic cancer, patients may die due to liver failure, severe infections, bowel obstruction, malnutrition and weakness, intense pain, and multiple organ failure. These conditions lead to the accumulation of toxins in the body, immune system failure, severe abdominal pain and vomiting, and decreased strength and immunity, ultimately resulting in death. During this stage, it is crucial to manage pain and provide palliative care to reduce suffering and improve the quality of life.

Regular Follow-Up Examinations

After pancreatic cancer treatment, patients need regular check-ups to monitor tumor recurrence and other health issues. These examinations may include abdominal ultrasounds, computed tomography (CT) scans, or magnetic resonance imaging (MRI). Regular follow-up is crucial for effective disease management.

Postoperative Care

After undergoing surgical treatment, patients should adhere to their physician’s recommendations and undergo regular check-ups and rehabilitation. This may include physical therapy, recovery training, and other therapeutic approaches. Additionally, postoperative dietary adjustments usually start with a liquid diet, gradually progress to a soft diet, and finally, include regular solid foods.

Reference

Websites related to caring for Pancreatic Cancer

This article is provided for informational purposes only regarding industry information. The development of new drugs involves lengthy timelines, high financial investments, and is not guaranteed to be successful. These factors may expose investors to risks, and therefore, investors should exercise caution and prudence when making investment decisions.