Locally Advanced Pancreatic Cancer
PALLIATIVE CARE
CASE CONTINUED
The patient is unable to tolerate his first round of second-line therapy with modified FOLFIRINOX. His overall treatment plan is transitioned to palliation. He continues to have pain, despite increasing doses of narcotics.
What is the next step for patients in whom second-line therapy fails and who have intractable pain while on high-dose narcotics?
A subset of patients with unresectable LAPC may not be amenable to chemotherapy with or without radiation due to significant comorbidities or because they present with or progress to ECOG scores 3 or 4. The goal in these patients should be palliation. Pain is one of the most predominant and difficult to manage symptoms in progressive LAPC. Opioid-based medications are the primary treatment for pain in LAPC. However, patients sometimes become refractory to opioid medications. In this group of patients, it is reasonable to consider palliative radiation as an alternative method for pain control.116
,An alternative to palliative radiation in the setting of progressive pain in PDA is celiac plexus block or neurolysis. By injecting an anesthetic or alcohol into the celiac plexus, neural signaling pathways involved in the propagation of pain are inhibited without leading to significant nerve destruction. Additionally, chemical splanchnicectomy allows for reduced opioid medication use and associated side effects.117
In general patients with LAPC have profound weight loss prior to and during treatment. This has significant implications prognostically and on treatment options. The underlying etiology is multifactorial, but one of the primary driving factors is pancreatic insufficiency. An estimated 65% of pancreatic cancer patients have fat malabsorption, and 50% have protein malabsorption, leading to steatorrhea and weight loss.118 Patients diagnosed with pancreatic cancer should be given enzyme replacement with formulations that include lipase, amylase, and protease. A minimum dose of enzyme replacement should include 40,000 to 50,000 U of lipase during meals and 25,000 U during snack intake. If maldigestion, symptoms, or nutritional endpoints (BMI, albumin, prealbumin, cholesterol) do not improve, the pancreatic enzyme dose should be escalated and a proton-pump inhibitor (PPI) added. In patients with pancreatic insufficiency, PPIs have been shown to improve fat absorption.119 Enzyme replacement therapy has been shown to prevent weight loss in patients with unresectable pancreatic cancer.120
As most patients with LAPC go on to develop progressive disease, palliative care becomes an integral aspect of the therapeutic paradigm. Palliation in LAPC has a significant role in determining quality of life and ensuring patient’s goals of care have been meet. Studies have suggested that pancreatic cancer is second only to lung cancer in terms of the number of emergency department visits in the later stages of disease.120 Additionally, aggressive care in the setting of incurable diseases such as LAPC has been associated with poor quality of life.121 More recently it has been shown that involvement of palliative care in patients with advanced pancreatic is associated with less aggressive care near death.122 Therefore, the incorporation of palliative or supportive care teams in the treatment of patients with progressive LAPC can improve quality of life and alleviate suffering associated with increasing symptom burden.
CONCLUSION
LAPC is a difficult disease for both provider and patient. There is a paucity of robust clinical trials in the neoadjuvant setting for LAPC. Current research is complicated by varying consensus definitions of resectability and the varying treatment configurations across studies. The optimal type, timing, and sequence of treatment and whether to add radiation therapy in LAPC have not been clearly defined. However, based on the available studies and consensus guidelines, patients who are deemed to have LAPC should have neoadjuvant therapy. FOLFIRINOX or gemcitabine with nab-paclitaxel should be considered first-line treatments. Patients with LAPC who respond to chemotherapy or are ineligible for multi-drug chemotherapy may benefit from chemoradiotherapy. In patients with unresectable disease, chemoradiotherapy has been shown to enhance survival as compared to best supportive care or radiation alone. For borderline resectable disease, it is reasonable to treat patients with either chemoradiotherapy, chemotherapy alone, or chemotherapy followed by chemoradiotherapy.
Considering the invasive nature of LAPC and the controversy around neoadjuvant treatment protocols, enrollment of patients with LAPC into clinical trials is important and will help determine the optimal treatment regimen for future patients.
