In Ontario, Canada, there are 1,200 new cases and deaths from pancreatic cancer each year in a population of 12 million people. In Ireland there are 400 new cases and deaths from pancreatic cancer in a population of 4 million annually.
Cancer has a High Prevalence in the Elderly
The average age for development of pancreatic cancer is over 70. This age distribution coupled with the disease causing significant morbidity, ensures the physician must deal with a vulnerable patient population. At least 60% of patients have metastatic disease at the time of diagnosis.
The survival time for these patients is about six months. Some 25% of patients are diagnosed with localised disease which is not resectable (not surgically removable), and is described as locally advanced disease. Less than 15% of patients have resectable cancer, yet survival is quite poor at 18 months generally and 98% of patients diagnosed with pancreatic cancer will die within five years. Effective systemic therapies must be focused on.
Pancreatic Cancer is due to Several Genetic Abnormalities
K-RAS is considered the signature mutation in pancreatic cancer occurring in 75–90% of cases with Hedgehog, aurora kinase, SMAD4 and p16 mutations ensuring a complicated malignancy. The average number of mutations was 63 [Science;321/5897/1801] . Treatments must include combination therapy, a personalised therapy and individual biological profiles of these specific changes.
Treatments with Gemcitabine and Folforinox
Gemcitabine was the first drug approved for treatment of pancreatic cancer and is now seen as a foundation for the modern treatment of the disease. Gemacitabine was combined with exatecan, irinotecan, pemetrexed, capecitabine and oxaliplatin, with some benefit from combination chemotherapy.
A clinically and statistically significant difference in favour of folfirinox [ASCO Conroy et al 2010, Abstract 4010] when compared to gemcitabine was recorded with a disease control rate of 70% versus 50%. Triple therapy studies using folfox, gemcitabine and nab-paclitaxel will be undertaken.
Targeted Therapy
More intensive chemotherapy is required to improve survival beyond one year. Targeted therapy with erlotinib with the Canadian National Cancer Institute (NCIC) gave positive results and has been approved [Journal of Clinical Oncology 25:1960-1966] for advanced metastatic pancreatic cancer.
There was a 23% improvement in overall survival.
The Future
Physicians must incorporate biology into clinical research. Tissue samples should be collected in order to understand what is happening at the biological level. Pancreatic cancer is a heterogenic disease, so, patients with different genetic profiles will require different approaches in their treatment. Within the last decade one year survival has improved from 2% to 25%. Folforinox data shows patients can reach one year survival rates at the 40% range. Chemotherapy has improved long term disease control.
Pancreatic cancer remains one of the worst cancers to be diagnosed with - the biological understanding of this cancer is paramount.
Sources
- CancerWorld
- Independent Pancreatic Cancer the Silent Killer
- This writer subscribes to CancerWorld and has written permission to use material from CancerWorld magazine.
Michael Manning - ' The best lack all conviction while the worst are full of passionate intensity' W.B.Yeats
