Albumin-bound paclitaxel (nab-paclitaxel) is effective in tumors that overexpress the albumin-binding protein secreted protein, acidic and rich in cysteine (SPARC), such as breast cancer, and used in pancreatic cancer (as this cancer also overexpresses SPARC). It is hypothesized, but not yet proven, that blockage of SPARC proteins in pancreatic cancer patients can affect tumor growth. The strategy here is to attack inflammatory stromal tissue. Pegylated recombinant human hyaluronidase (PEGPH20) represents another way to target the tumor stroma.17
Ruxolitinib, a janus kinase (JAK) inhibitor, decreases the production of inflammatory cytokines.
Immunotherapy research is ongoing, using anti-cytotoxic-leukocyte associated antigens 4 (anti-CTLA-4) and cancer vaccines.18,19
Research is increasing along many different avenues, and many other research approaches beyond the scope of this article are also underway, funded by the NCCN, private foundations such as the Lustgarten Foundation, and other groups.
SUPPORTIVE CARE
Supportive care aspects relevant to pancreatic cancer are biliary drainage and pain control.
Biliary Drainage
It is often necessary to place stents to improve bilirubin levels to relieve jaundice as well as obtain tissue or cells for diagnosis.20
Pain Control
Recent studies have shown that an inflammatory perineural invasion by pancreatic cancer cells leads to increased arborization and hypertrophy of the sensory nerves, helping to explain in part the severe pain experienced by patients.21 In addition to opioids, other options include radiation therapy and an image-guided celiac plexus block.22 The timing of when to start radiation treatments or use a block is not settled, but there is a consensus to consider these interventions earlier rather than later.
IMPLEMENTATION IN THE VA
There are no major barriers for obtaining the newer agents or combinations at the VA when they are indicated. Most of the agents in the Table are on the VA National Formulary, with the exception of nab-paclitaxel and erlotinib. When the requested agents are not in the formulary, the case is reviewed, and the agents are usually approved for use if they are appropriate for treatment according to national guidelines. Patient education about the risks and benefits of chemotherapy is important because some patients may decide against chemotherapy based on past undesirable experiences of relatives or friends with cancer. The major barrier to using the newer regimens is the patient’s poor general condition at diagnosis. If the diagnosis can be made earlier, before their general condition deteriorates significantly, the patients will have more treatment options and an improved outcome. More research is needed to find better treatments for this deadly disease.
CONCLUSIONS
Systemic chemotherapy provides benefit to patients with advanced pancreatic cancer. For the patientswith good performance status (ECOG PS 0 or 1), FOLFIRINOX or gemcitabine plus nab-paclitaxel are reasonable choices for first-line treatment. Gemcitabine plus nab-paclitaxel is an option for the patients with modest performance status who cannot tolerate the FOLFIRINOX regimen. For patients with poor performance status, gemcitabine as a single-agent or as supportive care may be offered. Although the new combination regimens are more effective than single-agent gemcitabine, the median survival is still < 1 year. More effective therapy is needed. Participation in clinical trials is encouraged.
Acknowledgements
I want to thank my colleagues Dr. Victor Chang and Dr. Basil Kasimis for their comments.
Author disclosures
The author reports no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the author and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
