Living Longer: Locally Advanced Pancreatic Cancer (I)

Introduction

Locally advanced pancreatic cancer:

  • Pancreatic cancer that is inoperable or borderline inoperable, normally due to tumor proximity or invasion to adjacent major blood vessels
  • Consists of 35% of pancreatic cancer at diagnosis
    • 15% have resectable disease Stage I, II and
    • 50% have metastatic disease Stage IV
  • Have slightly longer survival compared to cancer that already spread/ metastatic
Screen Shot 2018-06-06 at 10.51.50 PM
Pancreatic cancers are categorized on a continuum from resectable to unresectable according to the involvement of adjacent structures and the presence of distant metastases (NEJM 2014;371:1039-49

As long as the primary is not removed, CURATIVE treatment won’t be effective. Treatment intention will be as per stage 4 cancer, which is to CONTROL the disease, not cure.

Treatment for locally advanced pancreatic cancer

The standard of care treatment for locally advanced pancreatic cancer is single agent chemotherapy named gemcitabine (patented in 1983!) for 6 cycles

  • Gemcitabine achieved average survival of about 7 months (Burris HA, 1997).
  • Is very tolerable and I must admit I still use it on regular basis for my pancreatic cancer patients.

Subsequently, many studies tried adding another chemotherapy to gemcitabine to improve survival but failed.

It was not until combination with nab-paclitaxel able to improve average survival to 10 months (De Vita, 2018).

  • Gemcitabine and nab-paclitaxel combination treatment is well tolerated also.

If adding 2 different improve survival, it doesn’t take long for someone to come out with triple chemotherapy combination to improve outcome in advanced pancreatic cancer.

We often seen biologic or immunotherapy increasing survival by few months and it’s a breakthrough.

How often we see survival being doubled?

The triple chemotherapeutic regime is FOLFORINOX, combination of 5-FU, irinotecan and oxaliplatin.

  • Modified FOLFORINOX with lower dose and omiting bolus 5-FU was introduced later to reduce side effects and improve tolerability.
  • Average survival was doubled to 24 months (Suker, 2016). With the latest treatment, patients can now survive twice as long as before.
  • However, more than half (60%) reported grade 3 or 4 side effects, although there is no death reported.

The severity of side effects can be reduced with better supportive and prophylactic medications and patient education to seek treatment early before condition worsened.

  • eg. medication such as GCSF to increase total white blood cells is often given 24 hours after completion of chemotherapy in order to prevent neutropenia (low neutrophils – a component of white blood cells vital to fight of infections).

Indeed this is practice changing. Locally advanced pancreatic patients should receive this treatment (FOLFORINOX), if they have good performance status/ fit enough.

In fact, it doesn’t take any genius to just mention about this three treatment regimes. The secret sauce here is how to make sure patient able to:

  • complete treatment with maximum dose intensity
  • without any interruptions
  • confidently attend to all side effects, especially serious side effects, and make sure patients come out safely

The most important of all is the ability to recognise pancreatic tumor that has potential to be resected after chemotherapy.

Patient will have a chance a cure if the locally advanced tumor can be resected after ‘neoadjuvant’ chemotherapy.

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