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.
In Taiwan, the diagnosis rate of pancreatic cancer has increased over threefold in the past 20 years, with a 1.7-fold increase in mortality rate. There are over 2,500 new patients diagnosed annually, and it ranks seventh among the top ten leading causes of cancer-related deaths in the country in 2021, with a mortality rate of 11.3%. The 5-year survival rate for pancreatic cancer in Taiwan 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%.
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.
- Difficulty in early detection and high mortality rate: Pancreatic cancer is located in the retroperitoneal cavity at the back of the spine, and it often presents with no symptoms in the early stages. Many patients are already in the late or terminal stage of pancreatic cancer at the time of diagnosis, making complete resection challenging. Additionally, pancreatic cancer cells have aggressive characteristics, making them prone to metastasis and recurrence, resulting in a high mortality rate.
- 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.
- Symptoms to be mindful of include upper abdominal fullness, upper abdominal pain, weight loss, diarrhea, jaundice, and back pain, among others.
Diagnosis of Pancreatic Cancer
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.
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.
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.
Onivyde® (Irinotecan Liposomal Injection)
Onivyde® is a liposomal injection containing Irinotecan, a derivative of camptothecin and a cytotoxic drug widely approved and used in 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.
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).
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.
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.
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.
Pain Management
Pancreatic cancer frequently causes chronic pain in the upper abdomen or back, 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.
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.
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.
