Chemotherapy complication: methotrexate absorbed into the bloodstream after spinal injection

What happened, in summary

A woman in her 60s was diagnosed through screening mammography with grade 1 invasive ductal carcinoma of the left breast. The cancer was Stage IIA, pT2N0, and was oestrogen receptor-positive, progesterone receptor-positive and HER2-negative. Her Oncotype DX Recurrence Score was 20. She underwent partial mastectomy with sentinel-node biopsy and whole-breast radiation. Letrozole was later changed to exemestane because of side effects.

Her disease subsequently spread to the leptomeninges, the membranes surrounding the brain and spinal cord. She received abemaciclib and weekly intrathecal methotrexate. After 5 doses of methotrexate at 12 mg, she developed sharply reduced blood counts, fatigue and painful mouth ulcers. Although serum methotrexate remained at a low level, systemic absorption was considered the most likely cause. The sixth dose was held for 1 week and then reduced by 50% to 6 mg. Her mouth ulcers improved with the delay, dose reduction and medicated mouthwash. Abemaciclib was restarted after her platelet count recovered, during week 10 of intrathecal treatment.

Five months after the leptomeningeal diagnosis, she developed left-sided weakness and difficulty finding words. Brain MRI showed progression with a new 2 cm enhancing mass and surrounding swelling. She received intravenous dexamethasone and began whole-brain radiation. During the admission, her mental status became inconsistent and she could no longer make medical decisions.

After consultation with palliative care, her family chose comfort-focused treatment. She was discharged to inpatient hospice and died 10 days later. Her experience also showed that intrathecal methotrexate can produce systemic toxicity even when measured blood levels appear low.