Managing Toxicities of Therapy for Pancreatic Cancer

George Kim, MD:The toxicity profiles also help us decide which regimen to choose. That’s especially true in the community. So, for example, gemcitabine/Abraxane does have mild suppressions, neutropenia, thrombocytopenia, and then the neuropathy. These are symptoms that are well-managed either at a community center or an academic center. In comparison, FOLFIRINOX, if it is not given at the right dose modifications, for example, or if the patients aren’t followed closely—especially in pancreas cancer where, again, the patients start off with a compromised performance status—patients can really run into nausea, vomiting, diarrhea, dehydration, and neutropenia, which are very significant side effects. They really have to be managed very closely, and they can be catastrophic.

And then, you also have to recognize that pancreas cancer patients, their ability to bounce back and their reserve is compromised. So, if you knock a patient with FOLFIRINOX off their feet, they go to the hospital. Their ability to bounce back and get additional treatment is compromised. And so, you may have one shot to get this right.

With gemcitabine/Abraxane, I think the side effects are fairly well-managed. And, again, the regimen was evaluated in the community in the majority of the patients enrolled. So, we know that this is applicable or very useful for patients that we see in the clinic every day. It’s very important in how we select, especially when we’re out in the community.

With the treatment combination of gemcitabine and Abraxane, in patients with good performance status—PS 1s, and you can actually use in PS 2s—patients do well. Patients can tolerate the weekly schedule. We may need to make some dose adjustments, especially on day 8 or even day 15. We may have to alter the schedule, implement the week of rest sooner. We may have to change from a 3-week on/1-week off to a 2-week on/1-week off schedule. But these are some of the adjustments that can be made. We can make dose reductions in the Abraxane from the 125 mg/m²down to 100 mg/m², if that’s needed. And then, again, patients do fairly well. They do experience fatigue, which is typical of chemotherapy, but it could also be characteristic of pancreatic cancer.

The myelosuppression is well-managed. We can implement growth factors if we need to, either Neupogen or Neulasta. And then, there’s the neuropathy. It’s important to recognize that 17% of patients do get grade 3 neuropathy, which is characteristic of taxanes. The important consideration here is that patients, if you hold the Abraxane for up to 29 days and just give gemcitabine, the neuropathy will reduce to a level of 1 after that period, and about 44% of patients can go back on to treatment. So, these are all some of the management considerations when patients are undergoing treatment.

Obviously, you’re still focusing on what we talked about earlier: the need to maintain nutrition, maintain pain control, and really manage the bile duct stent, making sure it’s not occluded. Sometimes we’ll have to send in our gastroenterologist to clear out the stent. It does not always mean that the tumor is progressing into the stent, it just may be clogged with debris. And so, these are ongoing issues—DVT considerations, prophylaxis, all of these are the ongoing management that’s needed in treating patients with pancreatic cancer.

Transcript edited for clarity.

March 2016

• A 63-year-old Caucasian male was admitted to the hospital from the emergency room with symptoms of epigastric pain that radiated toward the back, abdominal distention, vomiting, and jaundice
• Laboratory tests:
  • Bilirubin and liver enzymes; elevated
  • CBC values WNL
  • Hepatitis B, & C testing, negative
  • CEA: 34.2 ng/mL; CA 19-9 > 12000 U/mL
• Performance status, 1
• CT reveals 3.5 cm × 3.7 cm mass in the head of the pancreas and multiple liver nodules; also, indicates an obstruction of the bile duct
• Ultrasound-guided percutaneous needle biopsy of a liver metastases shows adenocarcinoma histology
• The patient undergoes biliary stent placement based on endoscopic retrograde cholangiopancreatogram (ERCP) findings
• Diagnosis: stage IV pancreatic cancer with liver metastasis
• The patient was started with treatment on gemcitabine andnab-paclitaxel
• CT with contrast after two treatment cycles showed marked shrinkage of the pancreatic lesion and liver nodules.
• CT after 6 cycles showed stable disease

November 2016

• The patient reports symptoms of rapid weight loss, abdominal pain, dark urine, and jaundice; he has declining functional status and is often bedridden
• Systemic therapy is under consideration