Abstract

Paclitaxel induced mild derangement of liver functions including bilirubin, alkaline phosphatase, and AST has been infrequently noticed in clinical trials. Contrary to Paclitaxel, hepatocellular injury, hepatitis, and liver tenderness are common laboratory and clinical findings with Trastuzumab. However, hepatic failure/necrosis secondary to Paclitaxel or Trastuzumab has never been reported in literature. A 62-year-old lady, previously healthy, was treated with adjuvant therapy for left breast stage II, high grade invasive ductal carcinoma which was node negative, oestrogen receptor negative, progesterone receptor positive, and HER2 receptor positive. After modified radical mastectomy and axillary clearance, she finished four cycles of Doxorubicin/Cyclophosphamide chemotherapy and then commenced on Paclitaxel/Trastuzumab combination chemotherapy. Within twelve hours of first dose of Paclitaxel/Trastuzumab therapy, patient required hospital admission for acute onset respiratory failure. Patient died within 36 hours of therapy and autopsy was suggestive of acute hepatic necrosis without any other significant findings. Detailed investigations were not carried out as event was quick with rapid deterioration. There was no history of prior liver pathology/injury and preliminary investigations for major organ involvement were unremarkable. As per our knowledge, Paclitaxel and/or Trastuzumab induced acute hepatic necrosis has never been reported in literature before, hence difficult to predict.

Highlights

  • Paclitaxel (Taxol) is increasingly being used to treat ovarian and breast cancer [1, 2]

  • Trastuzumab is a humanised monoclonal immunoglobulin G1 kappa antibody that binds to the extracellular membrane domain of HER2 and inhibits the proliferation and survival of HER2-dependent tumours

  • According to the validated drug-induced hepatotoxicity scales [3,4,5,6], certain criteria should be met in order to prove that a liver injury is caused by the medication such as temporal relation between drug and liver injury, reversal of liver abnormality on cessation of drug, and exclusion of other determinants of liver injury and reproducibility

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Summary

Introduction

Paclitaxel (Taxol) is increasingly being used to treat ovarian and breast cancer [1, 2]. Trastuzumab (anti-HER2 therapy) has been used in both metastatic and adjuvant breast cancer and improves response rate, time to progression, and overall survival, approved for combination therapy with Taxol as well. Adjuvant therapy of Paclitaxel and Trastuzumab has been used in numerous trials, has been shown to have a high response rate, and is currently one of the standards of care. Reversible cardiotoxicity due to Trastuzumab is well known but severe congestive heart failure occurred in 0.6% of patients treated in HERA (BIG-0101) trial. Hepatocellular injury/hepatitis and liver tenderness were noted with Trastuzumab; hepatic failure has not been noted

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