The multiple sclerosis (MS) drug mitoxantrone may be associated with an increased risk of colorectal cancer, according to a study published in the May 11, 2016, online issue of Neurology. Mitoxantrone suppresses the immune system. It was first developed as a chemotherapy drug for certain cancers.
Mitoxantrone is used for aggressive types of relapsing-remitting or progressive MS that do not respond to other MS drugs. But its use is limited because previous studies have shown an increased risk of leukemia and heart damage.
The current study examined whether the drug increases the risk of other types of cancer. For the study, German researchers looked at all people with MS who were treated with mitoxantrone from 1994 to 2007 and followed them until 2010.
Of the 676 people, 37 people, or 5.5 percent, were diagnosed with cancer after taking the drug, including nine people with breast cancer, seven with colorectal cancer and four with acute myeloid leukemia, which has been associated with mitoxantrone.
The rate of leukemia was 10 times higher in the people treated with mitoxantrone than in the general population in Germany. The rate of colorectal cancer, which is cancer of the colon and rectum, was three times higher than that of the general population. For breast cancer and all other types of cancer, people who had taken mitoxantrone were no more likely to develop the diseases than those in the general population.
Of the seven people with colorectal cancer, three died from the cancer during the study. The four people with leukemia all went into remission after treatment and were alive at the end of the study.
The researchers also looked at whether factors such as how much of the drug people had received cumulatively and whether they also received other immunosuppressant drugs affected their risk of developing cancer. The only factor related to a higher risk of cancer was being older when starting to take the drug.
“Despite an increased risk of acute myeloid leukemia and colorectal cancer, the overall rate of cancer was low enough to justify still using this drug for people severely affected by MS if no better treatment is available,” said study author Mathias Buttmann, MD, of the University of Würzburg in Würzburg, Germany. “Mitoxantrone is the only approved treatment for people with secondary progressive MS without relapses and should be considered in people where the disease is evolving quickly. Also, many of the new and highly effective MS drugs are not available to people in a number of countries for economic reasons, so mitoxantrone is being used for people with very active relapsing forms of the disease.”
Buttmann noted that the study was relatively small and needs to be confirmed. If the results are confirmed, he said that colonoscopies should be given after treatment with the drug to screen for colorectal cancer, which can be treated more effectively when diagnosed earlier.
About this MS research
Funding: The study was supported by the University of Würzburg.
Source: Rachel Seroka – AAN Image Source: The image is credited to Blausen Medical Communications, Inc and is licensed CC BY 3.0. Original Research:Abstract for “Malignancies after mitoxantrone for multiple sclerosis: A retrospective cohort study” by Mathias Buttmann, Linda Seuffert, Uwe Mäder, and Klaus V. Toyka in eurology. Published online May 11 2016 doi:10.1212/WNL.0000000000002745
Malignancies after mitoxantrone for multiple sclerosis: A retrospective cohort study
Objective: To assess the therapy-related risk of malignancies in mitoxantrone-treated patients with multiple sclerosis.
Methods: This retrospective observational cohort study included all mitoxantrone-treated patients with multiple sclerosis seen at our department between 1994 and 2007. We collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010. Malignancy rates were compared to the German national cancer registry matched for sex, age, and year of occurrence.
Results: Follow-up was completed in 676 of 677 identified patients. Median follow-up time was 8.7 years (interquartile range 6.8–11.2), corresponding to 6,220 person-years. Median cumulative mitoxantrone dose was 79.0 mg/m2 (interquartile range 50.8–102.4). Thirty-seven patients (5.5%) were diagnosed with a malignancy after mitoxantrone initiation, revealing a standardized incidence ratio of 1.50 (95% confidence interval [CI] 1.05–2.08). Entities included breast cancer (n = 9), colorectal cancer (n = 7), acute myeloid leukemia (n = 4, 0.6%), and others (each entity n = 1 or 2). The standardized incidence ratio of colorectal cancer was 2.98 (95% CI 1.20–6.14) and of acute myeloid leukemia 10.44 (95% CI 3.39–24.36). It was not increased for other entities including breast cancer. Multivariate Cox regression identified higher age at treatment initiation but neither cumulative mitoxantrone dose (>75 vs ≤75 mg/m2) nor treatment with other immunosuppressive drugs or sex as a risk factor. Fifty-five patients had died, among them 12 of a malignancy and 43 reportedly of other causes.
Conclusions: While the overall incidence of malignancies was only mildly increased, the risk of leukemia and colorectal cancer was heightened. If confirmed, posttherapy colonoscopy could become advisable.
“Malignancies after mitoxantrone for multiple sclerosis: A retrospective cohort study” by Mathias Buttmann, Linda Seuffert, Uwe Mäder, and Klaus V. Toyka in eurology. Published online May 11 2016 doi:10.1212/WNL.0000000000002745