Pancreatic Cancer: Causes, Prevention, Prognosis, Diagnosis And Latest TreatmentPrevalence Pancreatic cancer is the fourth most common cause of adult cancer death, accounting for an estimated 42,470 new cases and 35,240 deaths in USA for 2009. The high mortality rate is due to the high incidence of metastatic disease at initial diagnosis, the aggressive clinical course and the failure of current therapies. Causes It is not clear what causes pancreatic cancer, but some risk factors have been linked to the disease. Modifiable risk factors that have been associated with pancreatic cancer include:
Prevention At this moment, there is no way to prevent pancreatic cancer. Similar to the prevention of other cancer, stop smoking, having a healthy diet and exercise are important in keeping pancreatic cancer at bay. Symptoms of pancreatic cancer It is very difficult to find pancreatic cancer early in the course of the disease since the pancreas lies deep inside the body and it is not easy to fell the tumors during a routine physical exam. Currently, there are no blood tests or other tests that can find the pancreatic cancer early in patients without symptoms. When a person has symptoms, the cancer is usually large and has spread to other organs. Thus, patients with pancreatic cancer usually have a poor outlook. Symptoms of pancreatic cancer include jaundice, abdomen pain (belly area), pain in the middle of the back, weight loss, pale and greasy stools, swollen gallbladder, blood clots and increase in blood sugar level. Physical exam To confirm whether the tumor is cancerous, the physician will need to do a biopsy to confirm the cell types. The physician might also examine your lymph nodes and conduct imaging tests such as CT, MRI, PET, endoscopic ultrasound, ERCP (endoscopic retrograde cholangiopancreatography) to see whether the tumor has spread to lymph nodes or distant organs. Prognosis Only 20% of the patients presenting with pancreatic cancer will the tumor be operable. The median disease-free survival following complete resection of pancreatic cancer and adjuvant administration of gemcitabine is 13.4 months versus 6.9 months for untreated patients. The longer disease-free survival after surgery and adjuvant chemotherapy, unfortunately, has not translated into any advantage in overall survival. For the other patients who had locally advanced (40%) or metastatic (40%) disease at diagnosis, the median survival is 8-12 months and 3-6 months respectively. Treatment Surgery Pancreatic cancer surgery is one of the hardest operations for surgeon and patients. Surgery results in complications and may take many weeks for patients to recover. There are 2 types of surgery used for pancreatic cancer:
Studies have shown that palliative surgery does not help most patients to live longer. Curative Surgery If the cancer is contained within the pancreas, the surgeon might conduct a Whipple procedure. In this surgery, the surgeon remove parts of the pancreas, parts of the stomach and small intestine, the gallbladder, part of the common bile duct, and some nearby lymph nodes. It is a very complex operation that carries high risk of complications and might be fatal. It is usually done by experienced surgeons who have done this many times. For patients who have surgery, the 5-year survival rate is only 20%. It is because a small number of cancer cells may already have spread to other parts of the body. Only a small number of pancreatic cancer patients (about 10%) has their cancer contains within the pancreas. Palliative surgery When the surgeon discovers that the tumor has spread and it is impossible to cure the patients, the surgeon may continue the operation as a palliative procedure to relieve the symptoms. For example, the surgeon may relieve blockage of the bile duct to relieve the pain and the problems with digestion. There are 2 options to relieve a bile duct blockage. One is to re-route the flow of bile from the common bile duct into the small intestine. This requires a large incision and it may take weeks for the patient to recover. An advantage is that during the surgery, the doctor may be able to cut the nerves leading to the pancreas and will reduce the pain for the patient. The second and the most popular way to treat bile duct blockage is to use metal tubes calledstentsto keep the bile duct open. The doctor puts the stents in through an endoscope. Bigger stents are also used to keep the small intestine open, too. Pharmacotherapy First-line therapy Gemcitabine (Gem)- Gemzar Gemcitabine is the gold standard chemotherapy for pancreatic cancer since its approval in 1996. The approval was based a phase III trial which involves 126 patients randomized either to gemcitabine or weekly injection of 5-fluorouracil (5-FU).
Gemcitabine + Oxaliplatin (GemOx) – Gemzar and Eloxatin For patients who like extend the time without disease progression and are willing to tolerate the adverse effects of chemotherapy may consider the GemOx regimen. GemOx was evaluated in 313 patients with advanced pancreatic cancer. Patients were randomly assigned to either GemOx or gemcitabine. At the end of the study, GemOx was superior to gemcitabine in
However, there was no difference in median overall survival (9.0 and 7.1 months for GemOx and Gem, respectively; P=0.13) Also, patients who were assigned to the GemOx arm had a higher incidence of grade 3 and 4 toxicity in platelets (14.0% for GemOx vs 3.2% for Gem), vomiting (8.9% for GemOx vs 3.2% for Gem) and neurosensory symptoms (19.1% for GemOx vs. 0% for Gem). Gemcitabine + Capecitabine (GemCap) – Gemzar and Xeloda GemCap is another alternative to gemcitabine for pancreatic cancer. However, results of two phase III trials showed conflicting results. The first trial randomized 319 patients to receive either GemCap or Gem.
Another phase III trial randomized 533 patients to receive gemcitabine plus capecitabine or gemictabine. The trial demonstrated a statistically significant improvement in overall survival time in the GemCap arm (7.4 months vs 6 months, p =0.0014). The result might be attributed to the prolonged administration of capecitabine. Erlotinib + Gemcitabine – Tarceva + Gemzar Beside chemotherapy, targeted therapy plus chemotherapy has also been shown to improved survival. Erlotinib, a targeted therapy, has been approved as treatment for locally advanced and metastatic pancreatic cancer patients. In a randomized, double-blind, phase III trial, 569 patients were randomly assigned to receive gemcitabine plus erlotinib or gemcitabine plus placebo.
Bevacizumab + Erlotinib + Gemcitabine – Avastin + Tarceva + Gemzar Another target regimen that has been tested is the bevacizumab plus erlotinib and gemcitabine. This regimen, however, have only been shown to improve progression-free survival (4.6 months vs. 3.6 months, p = 0.0002), but not overall survival (7.1 months vs. 6 months, p =0.2) when compared with erlotinib plus gemcitabine. Second-line therapy Oxaliplatin plus 5-FU and folinic acid (OFF regimen) Patients who failed first line gemcitabine can use the OFF regiment to control their disease. The CONKO 003 trial have shown that metastatic pancreatic patients whose disease had progressed from the first-line gemcitabine treatment, had significant survival benefit with the OFF regimen than the FF regimen (5-FU plus folinic acid). The progression-free survival was significantly different (p=0.012) and the median survival time from initiation of second-line therapy was 20 weeks for the OFF vs 13 weeks for the FF arms (p=0.014). Conclusions Pancreatic cancer remains a major challenge to the medical field. Only 10% of the pancreatic cancer patients have their cancer contained with the pancreas. This group of patients might be cured by surgery. The rest might need chemotherapy and targeted therapy to extend their survival. Gemcitabine is the standard 1st line therapy for pancreatic cancer. Patients with good performance status can also consider oxaliplatin + capecitabine to achieve prolonged survival. For patients who fail the first line treatment, oxaliplatin-5FU-folinic acid should be used to improve survival. In the adjuvant setting, current studies have supported the role of gemcitabine, either as monotherapy or in combination with chemoradiotherapy with 5-FU. Please visit us at healthreason.com for more health related articles. |