| Prevalence | | | | Gemcitabine is the gold standard chemotherapy |
| Pancreatic cancer is the fourth most common | | | | for pancreatic cancer since its approval in 1996. |
| cause of adult cancer death, accounting for an | | | | The approval was based a phase III trial which |
| estimated 42,470 new cases and 35,240 deaths | | | | involves 126 patients randomized either to |
| in USA for 2009. The high mortality rate is due | | | | gemcitabine or weekly injection of 5-fluorouracil |
| to the high incidence of metastatic disease at initial | | | | (5-FU). |
| diagnosis, the aggressive clinical course and the | | | | - Clinical response was experienced in 23.8% of |
| failure of current therapies. | | | | gemcitabine-treated patients compared with 4.8% |
| Causes | | | | of 5-Fu-treated patients (p=0.004) |
| It is not clear what causes pancreatic cancer, but | | | | - The median overall survival durations were 5.65 |
| some risk factors have been linked to the | | | | and 4.41 months for gemcitabine-treated and |
| disease. Modifiable risk factors that have been | | | | 5-FU-treated patients (p=0.003) |
| associated with pancreatic cancer include: | | | | - The 1 year survival rate was 18% and 2% for |
| - Smoking: Smokers have 2 to 3 times higher risk | | | | the gemcitabine and the 5-FU group, respectively |
| of getting pancreatic cancers.. About 2 to 3 out | | | | (p=0.0009) |
| of 10 cases of pancreatic cancer are thought to | | | | Gemcitabine + Oxaliplatin (GemOx) – Gemzar |
| be caused by smoking. | | | | and Eloxatin |
| - Obesity and lack of exercise: Overweight people | | | | For patients who like extend the time without |
| and those who don't get much exercise are more | | | | disease progression and are willing to tolerate the |
| likely to develop pancreatic cancer. | | | | adverse effects of chemotherapy may consider |
| - Diabetes: Patients with type 2 diabetes have an | | | | the GemOx regimen. GemOx was evaluated in |
| increase risk of getting pancreatic cancer. | | | | 313 patients with advanced pancreatic cancer. |
| - Chronic pancreatitis: Some patients with chronic | | | | Patients were randomly assigned to either |
| pancreatitis develop pancreatic cancer | | | | GemOx or gemcitabine. |
| - Cirrhosis of the liver: People with cirrhosis due to | | | | At the end of the study, GemOx was superior to |
| hepatitis and alcohol consumption seem to have | | | | gemcitabine in |
| an increased risk of pancreatic cancer. | | | | - Response rate (26.8% vs 17.3% for GemOx |
| - Work exposure: Heavy exposure to certain | | | | and Gem, respectively; p=0.04) |
| pesticides, dyes, and chemicals may increase the | | | | - Progression-free survival (5.8 vs 3.7 months for |
| risk of getting pancreatic cancer. | | | | GemOx and Gem, respectively; p=0.04) |
| - Stomach problems: Having too much stomach | | | | - Clinical benefit (5.8 vs. 3.7 months for GemOx |
| acid or having bacteria called H. pylori in the | | | | and Gem, respectively; p=0.04) |
| stomach may increase the risk of pancreatic | | | | However, there was no difference in median |
| cancer. | | | | overall survival (9.0 and 7.1 months for GemOx |
| Prevention | | | | and Gem, respectively; P=0.13) |
| At this moment, there is no way to prevent | | | | Also, patients who were assigned to the GemOx |
| pancreatic cancer. Similar to the prevention of | | | | arm had a higher incidence of grade 3 and 4 |
| other cancer, stop smoking, having a healthy diet | | | | toxicity in platelets (14.0% for GemOx vs 3.2% |
| and exercise are important in keeping pancreatic | | | | for Gem), vomiting (8.9% for GemOx vs 3.2% |
| cancer at bay. | | | | for Gem) and neurosensory symptoms (19.1% |
| Symptoms of pancreatic cancer | | | | for GemOx vs. 0% for Gem). |
| It is very difficult to find pancreatic cancer early in | | | | Gemcitabine + Capecitabine (GemCap) – |
| the course of the disease since the pancreas lies | | | | Gemzar and Xeloda |
| deep inside the body and it is not easy to fell the | | | | GemCap is another alternative to gemcitabine for |
| tumors during a routine physical exam. Currently, | | | | pancreatic cancer. However, results of two |
| there are no blood tests or other tests that can | | | | phase III trials showed conflicting results. |
| find the pancreatic cancer early in patients without | | | | The first trial randomized 319 patients to receive |
| symptoms. | | | | either GemCap or Gem. |
| When a person has symptoms, the cancer is | | | | - There was no difference in median overall |
| usually large and has spread to other organs. | | | | survival time between the two arms (8.4 and 7.2 |
| Thus, patients with pancreatic cancer usually have | | | | months in the Gem Cap and Gem arms |
| a poor outlook. | | | | respectively; p=0.234). |
| Symptoms of pancreatic cancer include jaundice, | | | | - Frequency of grade 3 or 4 adverse events, |
| abdomen pain (belly area), pain in the middle of | | | | including neutropenia, was similar in both |
| the back, weight loss, pale and greasy stools, | | | | arms. |
| swollen gallbladder, blood clots and increase in | | | | - Post hoc analysis reviewed that patients in the |
| blood sugar level. | | | | GemCap arm with good Karnofsky performance |
| Physical exam | | | | status experienced a significant prolongation of |
| To confirm whether the tumor is cancerous, the | | | | median overall survival time when compared with |
| physician will need to do a biopsy to confirm the | | | | the Gem arm (10.1 vs 7.4 months, respectively; |
| cell types. | | | | P=0.014) |
| The physician might also examine your lymph | | | | Another phase III trial randomized 533 patients to |
| nodes and conduct imaging tests such as CT, | | | | receive gemcitabine plus capecitabine or |
| MRI, PET, endoscopic ultrasound, ERCP | | | | gemictabine. The trial demonstrated a statistically |
| (endoscopic retrograde cholangiopancreatography) | | | | significant improvement in overall survival time in |
| to see whether the tumor has spread to lymph | | | | the GemCap arm (7.4 months vs 6 months, p |
| nodes or distant organs. | | | | =0.0014). The result might be attributed to the |
| Prognosis | | | | prolonged administration of capecitabine. |
| Only 20% of the patients presenting with | | | | |
| pancreatic cancer will the tumor be operable. | | | | Erlotinib + Gemcitabine – Tarceva + Gemzar |
| The median disease-free survival following | | | | Beside chemotherapy, targeted therapy plus |
| complete resection of pancreatic cancer and | | | | chemotherapy has also been shown to improved |
| adjuvant administration of gemcitabine is 13.4 | | | | survival. Erlotinib, a targeted therapy, has been |
| months versus 6.9 months for untreated | | | | approved as treatment for locally advanced and |
| patients. The longer disease-free survival after | | | | metastatic pancreatic cancer patients. |
| surgery and adjuvant chemotherapy, | | | | In a randomized, double-blind, phase III trial, 569 |
| unfortunately, has not translated into any | | | | patients were randomly assigned to receive |
| advantage in overall survival. | | | | gemcitabine plus erlotinib or gemcitabine plus |
| For the other patients who had locally advanced | | | | placebo. |
| (40%) or metastatic (40%) disease at diagnosis, | | | | - Overall median survival was significantly |
| the median survival is 8-12 months and 3-6 | | | | prolonged by 2 weeks in the erlotinbi/gemcitabine |
| months respectively. | | | | arm (6.2 months vs. 6.0 months, p=0.028). |
| Treatment | | | | - One-year survival was also greater with erlotinib |
| Surgery | | | | plus gemcitabine arm (24% vs. 19%; p =0.023). |
| Pancreatic cancer surgery is one of the hardest | | | | - Progression-free survival was significantly longer |
| operations for surgeon and patients. Surgery | | | | with erlotinib plus gemcitabine (3.75 months vs. |
| results in complications and may take many | | | | 3.55 months, p = 0.004). |
| weeks for patients to recover. | | | | - Of the 282 patients who received erlotinib, 79 |
| There are 2 types of surgery used for pancreatic | | | | had no rash, 102 had grade 1 rash, and 101 had a |
| cancer: | | | | grade 2 or higher skin rash. |
| - Curative surgery when it looks like it is possible | | | | - The occurrence of skin rash was associated |
| to remove all the cancer. | | | | with a significant and clinically meaningful difference |
| - Palliative surgery may be done if tests show | | | | in survival. The median survival rates for |
| that the tumor is too widespread to be | | | | patients with grade 0, 1, and 2 rash were 5.3, 5.8, |
| completely removed. In this case, surgery is | | | | and 10.5 months and the 1-year survival rate |
| done to relieve symptoms or to prevent the | | | | were 19%, 9% and 43%, respectively (p=0.001). |
| blockage of the bile ducts or the intestine by the | | | | |
| cancer. | | | | Bevacizumab + Erlotinib + Gemcitabine – |
| Studies have shown that palliative surgery does | | | | Avastin + Tarceva + Gemzar |
| not help most patients to live longer. | | | | Another target regimen that has been tested is |
| Curative Surgery | | | | the bevacizumab plus erlotinib and gemcitabine. |
| If the cancer is contained within the pancreas, the | | | | This regimen, however, have only been shown to |
| surgeon might conduct a Whipple procedure. In | | | | improve progression-free survival (4.6 months vs. |
| this surgery, the surgeon remove parts of the | | | | 3.6 months, p = 0.0002), but not overall survival |
| pancreas, parts of the stomach and small | | | | (7.1 months vs. 6 months, p =0.2) when |
| intestine, the gallbladder, part of the common bile | | | | compared with erlotinib plus gemcitabine. |
| duct, and some nearby lymph nodes. It is a very | | | | Second-line therapy |
| complex operation that carries high risk of | | | | Oxaliplatin plus 5-FU and folinic acid (OFF regimen) |
| complications and might be fatal. It is usually | | | | Patients who failed first line gemcitabine can use |
| done by experienced surgeons who have done | | | | the OFF regiment to control their disease. The |
| this many times. | | | | CONKO 003 trial have shown that metastatic |
| For patients who have surgery, the 5-year | | | | pancreatic patients whose disease had progressed |
| survival rate is only 20%. It is because a small | | | | from the first-line gemcitabine treatment, had |
| number of cancer cells may already have spread | | | | significant survival benefit with the OFF regimen |
| to other parts of the body. Only a small number | | | | than the FF regimen (5-FU plus folinic acid). |
| of pancreatic cancer patients (about 10%) has | | | | The progression-free survival was significantly |
| their cancer contains within the pancreas. | | | | different (p=0.012) and the median survival time |
| Palliative surgery | | | | from initiation of second-line therapy was 20 |
| When the surgeon discovers that the tumor has | | | | weeks for the OFF vs 13 weeks for the FF arms |
| spread and it is impossible to cure the patients, | | | | (p=0.014). |
| the surgeon may continue the operation as a | | | | Conclusions |
| palliative procedure to relieve the symptoms. For | | | | Pancreatic cancer remains a major challenge to |
| example, the surgeon may relieve blockage of | | | | the medical field. Only 10% of the pancreatic |
| the bile duct to relieve the pain and the problems | | | | cancer patients have their cancer contained with |
| with digestion. | | | | the pancreas. This group of patients might be |
| There are 2 options to relieve a bile duct | | | | cured by surgery. The rest might need |
| blockage. One is to re-route the flow of bile from | | | | chemotherapy and targeted therapy to extend |
| the common bile duct into the small intestine. This | | | | their survival. |
| requires a large incision and it may take weeks | | | | Gemcitabine is the standard 1st line therapy for |
| for the patient to recover. An advantage is that | | | | pancreatic cancer. Patients with good |
| during the surgery, the doctor may be able to cut | | | | performance status can also consider oxaliplatin + |
| the nerves leading to the pancreas and will reduce | | | | capecitabine to achieve prolonged survival. |
| the pain for the patient. | | | | For patients who fail the first line treatment, |
| The second and the most popular way to treat | | | | oxaliplatin-5FU-folinic acid should be used to |
| bile duct blockage is to use metal tubes called | | | | improve survival. |
| stents to keep the bile duct open. The doctor | | | | In the adjuvant setting, current studies have |
| puts the stents in through an endoscope. Bigger | | | | supported the role of gemcitabine, either as |
| stents are also used to keep the small intestine | | | | monotherapy or in combination with |
| open, too. | | | | chemoradiotherapy with 5-FU. |
| Pharmacotherapy | | | | |
| First-line therapy | | | | Please visit us at for more health related articles. |
| Gemcitabine (Gem)- Gemzar | | | | |