GRACE :: Pancreatic Cancer

Advanced Pancreatic Cancer: Changing Landscape Signals Hope

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Pancreatic cancer, though relatively uncommon, is the fourth most common of cancer-related deaths. In the United States, 44,030 new cases of pancreatic cancer were diagnosed with 37,660 deaths in 2011. The average estimated five-year survival of a pancreatic cancer patient with advanced stage of the cancer is 5% or less. Despite these grim figures, a number of recent developments in basic and clinical research offer hope for the future.

Patients with advanced pancreatic cancer include those with cancer spread to liver or other distant organs. In these cases, surgery or radiations are not feasible and chemotherapy remains the sole treatment option. For the past ten years, gemcitabine chemotherapy has been the mainstay for patients with advanced, stage IV pancreatic cancer. The approval of gemcitabine by the F.D.A. was based on an improved survival over the previous standard, 5-fluorouracil chemotherapy. Gemcitabine also led to a ‘clinical benefit response’, or an improvement in pain, appetite, weight and quality of life. In the past decade, there have been several clinical trials, which combined gemcitabine chemotherapy with other chemotherapy agents used in pancreatic cancer. All of these trials indicated that when gemcitabine was combined with another chemotherapy agent (gemcitabine + drug X), the resultant survival was no better than with gemcitabine alone.

The only recent success of gemcitabine-based chemotherapy was gemcitabine plus erlotinib (a targeted drug that acts against EGFR, a receptor on the surface of cancer cells), a combination that was superior to single-agent gemcitabine. In this study, the addition of erlotinib increased survival by an average of two weeks only. However, patients who developed significant skin rash from erlotinib actually lived an average of four months longer. Thus a valuable lesson was learned from this trial: some patients experience greater benefit from targeted drugs like erlotinib than others and we may be able to predict who those patients are based on the toxicity-skin rash.  Of course, the hope is that we may be able to select appropriate therapy earlier, before the occurrence of skin rash!

An important recent development in this field was the trial of a chemotherapy combination called FOLFIRINOX (consisting of 3 drugs- 5-fluorouracil, irinotecan and oxaliplatin), which was investigated in a clinical trial conducted in Europe. In this study, FOLFIRINOX resulted in improvement in survival for patients with advanced pancreatic cancer as compared with gemcitabine. FOLFIRINOX is more toxic than gemcitabine and is only meant for those patients with pancreatic cancer who are strong, younger and without any abnormality of liver functions. If administered to the wrong patient, FOLFIRINOX can be life threatening. While the FOLFIRINOX regimen is certainly an advance on gemcitabine for pancreatic cancer, one wonders if adding multiple toxic chemotherapeutic drugs is the only option we can offer in 2012, when the human genome is being unraveled.

One reason for the poor outcome in this disease is its heterogeneity at the genetic level. The hope in this disease lies in the ability to identify the heterogeneity in the patients and in the “personalization” of therapy. For instance, BRCA gene mutations are commonly associated with breast or ovarian cancers. A minority of these patients also have pancreatic cancer. Pancreatic cancer patients with this type of mutation (BRCA or its variants) appear to respond very well to a group of novel drugs called PARP inhibitors, and also to cisplatin and mitomycin. This is one of the first instances of personalized therapies for pancreatic cancer. Personalized therapy is already a reality in some cancers such as leukemia, breast cancer and for certain types of lung cancers. In the future, as more genetic information from pancreatic cancer becomes available, we will see additional examples of personalized therapy for this difficult disease.


2 Responses to Advanced Pancreatic Cancer: Changing Landscape Signals Hope

  • Colleen20 says:

    Thank you for your very respected opinions and thank you to all the well wishers.

  • patt says:

    My 32year old daughter has stage IV pancreatic cancer. Four treatments of Gemcitabine and Abraxane given ever other week is not showing promise. A mutation was found to be treatable with crizotinib and I am wondering if you have used or know of this drug for pancreatic cancer and whar the results were.

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