Patients with Advanced Pancreatic Cancer and Hyperbilirubinaemia: Review and German Expert Opinion on Treatment with nab-Paclitaxel plus Gemcitabine

Abstract

In patients with advanced unresectable pancreatic cancer, the prognosis is generally poor. Within recent years, new treatment options such as the FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) or the combination of nanoparticle albumin-bound (nab)-paclitaxel plus gemcitabine have shown a clinically relevant survival benefit over the standard gemcitabine in patients with good performance status. Unfortunately, patients with hyperbilirubinaemia, who constitute a substantial proportion of the pancreatic cancer patients, have been excluded from most clinical studies. Consequently, our knowledge on the appropriate medical treatment of this patient group is limited. In a meeting of German medical oncology experts, the available clinical evidence and own clinical experience regarding the management of patients with advanced pancreatic cancer and hyperbilirubinaemia was discussed. The present publication summarises the discussion outcomes with regard to appropriate management of these patients, including consensus-based recommendations for nab-paclitaxel/gemcitabine treatment, according to the best available evidence. In summary, knowledge of the underlying aetiology of hyperbilirubinaemia and the metabolisation routes of the cytotoxic drugs is crucial before initiating chemotherapy. As effective treatment options should also be made available to patients with comorbid conditions, including hyperbilirubinaemia, the experts provide advice for an initial dose reduction of chemotherapy with nab-paclitaxel/gemcitabine based on the total bilirubin level in patients with biliary obstruction or extensive liver metastasis.

Mendelian randomisation study of the effects of known and putative risk factors on pancreatic cancer

“…Alongside genetic variability,4–12 several PDAC epidemiological risk factors have been identified, through cohort studies and case–control studies with varying levels of evidence. Some are considered established: chronic pancreatitis,13 diabetes mellitus,14 obesity,15 glycaemic index,16 adiponectin level,17 lipid levels,18 19 alcohol consumption20 and smoking behaviour,20 while others are suggested: bilirubin level,21 22 vitamin D level23 and Helicobacter pylori infection 24. A small number of protective factors such as allergies,25 intake of statins26 and of aspirin27 have also been suggested.…”

Efficacy of Nab-Paclitaxel Plus Gemcitabine and Prognostic Value of Peripheral Neuropathy in Patients with Metastatic Pancreatic Cancer

“…Since nab-P/Gem can pharmacokinetically cause hepatic impairment, care must be taken in patients with hepatic impairment and hyperbilirubinemia, and those patients should be monitored frequently. 23 Results of this study demonstrated that elevated bilirubin and transaminases were not significantly related to OS, suggesting that abnormal laboratory findings caused by malignant biliary obstruction and liver metastasis in patients with MPC are not an absolute contraindication for chemotherapy, but rather an integral part of the inclusion criteria.…”

Serum miR‑210‑3p can be used to differentiate between patients with pancreatic ductal adenocarcinoma and chronic pancreatitis

“…Studies using larger cohorts are thus required to determine/confirm the reliability of these miRs as markers to use to differentiate between these two pathologies. In ~70% of cases of pancreatic cancer, the cancer is located within the pancreatic head and the majority of patients develop obstructive cholestasis resulting in increased ALP and GGTP serum levels (23). Significant positive correlations were identified between the expression of miR-210-3p and the activities of the cholestasis-related enzymes ALP and GGTP in patients with PDAC.…”