Limitations
cancer, death
CANCER, TUMOR GROWTH, RARE DISEASE, COMPLICATION
This study has some limitations. The trial was initially planned for enrollment of 30 patients to have complete data for 24 patients, providing 80% power for the primary end point. However, accrual in this rare disease was slow, with only 24 patients enrolled after 8 years (2013 to 2021). When designed in 2012, there was concern that delaying start of treatment would harm patients, thus the only prespecified interim analyses concerned increased death or severe complication in the observation first group. Although not prespecified, since the trial was not blinded, interim efficacy analysis was performed after 8 years; given complete lack of response to chemotherapy and no difference in tumor growth between observation and treatment periods, the trial was closed, as it was felt unethical to continuing treating patients with low-grade AA with fluorouracil-based chemotherapy. This trial was under the institutional data and safety monitoring board oversight for annual review of safety and efficacy. With the data and safety monitoring board’s permission, the trial was administratively closed. All of the patients in the study were enrolled at a tertiary referral cancer center, which may not be representative of patients in a community oncology practice. Despite these limitations, our study represents the first prospective, randomized trial for low-grade AA, to our knowledge.