Safety and efficacy of Nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer suffering from cholestatic hyperbilirubinaemia-A retrospective analysis

Eur J Cancer. 2018 Sep;100:85-93. doi: 10.1016/j.ejca.2018.06.001. Epub 2018 Jul 4.

Abstract

Introduction: Treatment of patients with advanced pancreatic carcinoma (APC) and hyperbilirubinaemia is problematic because these patients were regularly excluded from clinical studies. Nanoparticle albumin-bound paclitaxel and gemcitabine (nab-P/G) is an evidence-based treatment for patients with APC. This retrospective study investigated the safety and efficacy of nab-P/G in patients with APC and cholestatic hyperbilirubinaemia.

Methods: We screened our prospective database for patients with APC treated with nab-P/G at total bilirubin levels of ≥1.2 mg/dl. Patients were assigned into three groups according to their bilirubin level (A: 1.2-3 mg/dl, B: >3-5 mg/dl, C: >5 mg/dl). Analyses with regard to safety and survival were performed.

Results: Twenty-nine of 168 patients screened between Dec 2013 and Dec 2015 fulfilled the inclusion criteria. Most patients (83%) were male; median age was 63 [41-79] years. Nab-P/G administrations in patients with an elevated bilirubin level (median, range) did not result in unexpected toxicities assessed by predefined (non-)haematological parameters. Median overall survival (mOS) for the whole group was 11.7 (95% confidence interval [CI]: 6.8-14.0) months; for A: 11.8 (95% CI: 6.5-16.5), B: 9.2 (95% CI: 1.1 - NA) months and C 11.8 (95% CI: 5.9-20.0] months (p = 0.843). Again, mOS from the first application of nab-P/G did not differ between the groups (p = 0.13).

Conclusion: Nab-P/G administrations in our pts with cholestatic hyperbilirubinaemia suffering from APC were feasible and safe with respect to individualised dose administrations. A multicenter phase 1 trial in pts with hyperbilirubinaemia is started (AIO-PAK-0117) to confirm these findings in a prospective setting.

Keywords: Advanced pancreatic carcinoma; Chemotherapy; Cholestasis; Gemcitabine; Hyperbilirubinaemia; Nab-paclitaxel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Albumins / administration & dosage*
  • Albumins / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cholestasis / diagnosis
  • Cholestasis / etiology*
  • Cholestasis / mortality
  • Databases, Factual
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Feasibility Studies
  • Female
  • Humans
  • Hyperbilirubinemia / diagnosis
  • Hyperbilirubinemia / etiology*
  • Hyperbilirubinemia / mortality
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage*
  • Paclitaxel / adverse effects
  • Pancreatic Neoplasms / complications
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Deoxycytidine
  • gemcitabine
  • Paclitaxel