Background Regorafenib is the third line of treatment used in metastatic colon cancer. One of the most frequent adverse effects of regorafenib is thrombocytopenia that occurred as grade 4 in only 0.4% of patients treated in the CORRECT trial.

Purpose To describe the relationship between the occurrence of severe thrombocytopenia in a patient with metastatic colon cancer treated with regorafenib.

Material and methods The physician reported to our pharmacy department a severe thrombocytopenia case in a patient treated with regorafenib. The medical history was reviewed to evaluate the possible causality by the Karch-Lasagna algorithm.

Results A 62-year-old man, diagnosed with colorectal adenocarcinoma, was treated with firstline FOLFOX and bevacizumab and secondline FOLFIRI and aflibercept. Oxaliplatin and bevacizumab had to be discontinued due to feet and hand neuropathy and pulmonary embolism, respectively, and enoxaparin was added. In May 2015, adrenal and pulmonary nodules increased in size and the patient started treatment with regorafenib 120 mg/day for 3 weeks, in 28 day cycles. At this time, platelet count was normal (329 000 cells/µL). After 1 month the patient presented grade 1 diarrhoea, 5 kg of weight loss and 155 000 platelets/µL. 2 months later a control blood test showed severe thrombocytopenia (9000 platelets/μL) that was confirmed in two further analyses. Both regorafenib and enoxaparin were discontinued and a pool of platelets was administered. The clinicians prescribed prednisone 100 mg/24 h for 2 weeks continuing the downward pattern. Substantial improvement was observed 7 days later (38 000 platelets/µL) and in mid-August normal levels returned.

The modified Karch-Lasagna algorithm established a ‘probable’ relationship between severe thrombocytopenia and regorafenib treatment in this patient due to the fact of the temporal relationship between the start of treatment with regorafenib and thrombocytopenia occurrence, as well as between treatment discontinuation and improvement in thrombocytopenia.

Conclusion Despite being an adverse effect described in the data sheet and clinical trials, this episode of thrombocytopenia was very severe and forced discontinuation of regorafenib and change to another therapy. It was reversible and improved with prednisone. This reaction was reported to the Regional Pharmacovigilance Centre.

References and/or Acknowledgements

1. Grothey A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomized, placebo-controlled, phase 3 trial. Lancet 2013;381:303-12.

References and/or AcknowledgementsNo conflict of interest.