Microangiopathy associated with gemcitabine: a drug interaction with nab-paclitaxel? A case series and literature review

• DOI: 10.1007/s00228-022-03324-z
• Publication Date: 2022-05-04T06:03:24Z
• Authors: Jeanne Allard; Mathilde Bonnet; Lucie Laurent; Mohamed Bouattour; Marie-Pauline Gag...; Vincent Leclerc
• Keywords: Paclitaxel; Thrombotic Microangiopathies; Adenocarcinoma; Deoxycytidine; Gemcitabine; 3. Good health; Pancreatic Neoplasms; Mice; 03 medical and health sciences; 0302 clinical medicine; Albumins; Antineoplastic Combined Chemotherapy Protocols; Animals; Humans; Drug Interactions

Gemcitabine and nab-paclitaxel association can be used in first- or second-line treatment for metastatic pancreatic adenocarcinoma. Here, we report five cases of supposed gemcitabine-induced thrombotic microangiopathy (G-TMA), four of them with nab-paclitaxel. We assumed that nab-paclitaxel could be responsible for a potential drug interaction with gemcitabine, increasing the risk of thrombotic microangiopathy occurrence.Clinicians reported cases of supposed G-TMA that were declared to the Pharmacovigilance center. We collected the patients' data (clinical and biological characteristics), calculated an incidence rate of G-TMA in our center, and a Naranjo score for each patient. We also reviewed literature on a potential drug interaction between nab-paclitaxel and gemcitabine.Four patients were treated with nab-paclitaxel/gemcitabine and one with gemcitabine alone. The time onset of supposed G-TMA was 2 to 11 months. Patients developed anemia, thrombocytopenia, and renal failure. The incidence rate of supposed G-TMA was 2.7% in our center compared to 0.31% (Meyler's Side Effect of Drugs) and 0.01% in the gemcitabine's summary of product characteristics. Literature review outlined an increase of gemcitabine's plasmatic concentrations induced by nab-paclitaxel (Drugs® website) and a potentiation of gemcitabine's effect by nab-paclitaxel in murine models. This study showed that nab-paclitaxel inhibits cytidine deaminase's activity (responsible for gemcitabine's metabolism) and increases gemcitabine's active metabolite concentrations (gemcitabine triphosphate) in tumor tissues.High incidence rate of G-TMA was observed in our cohort due to a potential drug interaction between nab-paclitaxel and gemcitabine with an increased risk of developing G-TMA. Additional pharmacological and pharmaco-epidemiological investigations are mandatory to explore this hypothesis.