Mitoxantrone for MS linked to colorectal cancer risk

By Lucy Piper

Treatment with mitoxantrone for multiple sclerosis (MS) carries only a mildly increased risk of malignancy overall, but the risk of colorectal cancer and leukaemia is heightened, researchers have found.

They report a threefold increased incidence of colorectal cancer and a 10-fold increased incidence of acute myeloid leukaemia (AML) among 37 of 676 MS patients who were diagnosed with a malignancy over a median 8.7 years after starting mitoxantrone treatment.

The team, led by Mathias Buttmann (University of Würzburg, Germany), notes that colorectal cancer appeared to be the more life-threatening adverse effect, with three of seven affected patients dying from the tumour, whereas all four patients with AML experienced full remission after treatment.

"[P]osttreatment colonoscopy might improve the risk-benefit ratio of this highly active immunosuppressive drug", they recommend in Neurology.

Among the 5.5% of patients diagnosed with a malignancy, nine developed breast cancer, seven colorectal cancer and four AML, and there were also two cases each of glioblastoma multiforme, lung, pancreatic and prostate cancer, and one case each of nine other types of cancer.

The overall standardised incidence ratio for any type of malignancy was 1.5 compared with the general population, and other than colorectal cancer and AML no other specific cancer type was associated with a significantly increased risk.

For the majority of patients, mitoxantrone was administered at a dose of 12 mg/m² every 3 months, while 152 patients received induction therapy with three monthly cycles of 12 mg/m² followed by maintenance infusions of 5 mg/m² every 3 months once clinical stabilisation had occurred.

Neither cumulative mitoxantrone dose (>75 vs ≤75 mg/m²) nor treatment with other immunosuppressive drugs increased the risk of malignancy. There was also no association with gender. But the risk did increase 1.55-fold with every 5-year increase in age at treatment initiation.

Among the 55 patients who died over the 6220 person-years of follow-up, 12 did so from a malignancy and 43 from other causes.

Buttmann and colleagues note that "[m]itoxantrone is currently the only approved treatment for patients with secondary progressive MS without superimposed relapses and should be considered in patients with rapidly evolving disabling disease."

The overall incidence of all malignancies "appears acceptably low to justify mitoxantrone treatment in severely affected patients with MS if no better therapeutic alternative is available", they conclude.

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