12-05-2025
Anal Cancer Outcomes Improve on Lower-Dose Chemoradiotherapy
In the multicenter PLATO-ACT4 trial, patients with early-stage anal cancer who received reduced-dose chemoradiotherapy had higher complete clinical response rates at 6 months and experienced less acute toxicity than those who received the standard dose.
METHODOLOGY:
High radiation doses may lead to overtreatment in patients with early-stage anal cancer. This trial evaluated whether a reduced-dose regimen could maintain local control while minimizing toxicity.
Researchers conducted a phase 2, multicenter, randomized controlled trial involving patients with early-stage squamous cell carcinoma of the anus at 28 tertiary referral centers across the United Kingdom. A total of 160 patients were included in the primary analysis (median age, 66 years).
Patients were randomly assigned 1:2 to receive either standard dose (n = 55; 50.4 Gray in 28 fractions) or reduced dose (n = 105; 41.4 Gray in 23 fractions) intensity-modulated radiotherapy. In all patients, mitomycin (12 mg/m 2 ; maximum dose, 20 mg) was administered intravenously on day 1, and capecitabine (825 mg/m 2 ) orally twice daily on radiotherapy days.
; maximum dose, 20 mg) was administered intravenously on day 1, and capecitabine (825 mg/m ) orally twice daily on radiotherapy days. The primary endpoint was 3-year locoregional failure rates. This study presented the trial's short-term endpoints, including compliance with radiotherapy and chemotherapy, acute toxicities, clinical response rates at 3 and 6 months, and patient-reported outcomes up to 6 months from the start of treatment.
TAKEAWAY:
At 6 months, complete clinical response rates were 92% in the reduced-dose group and 87% in the standard-dose group.
Acute toxicity of grade 3 or higher occurred in fewer patients in the reduced-dose group — 35% vs 46% in the standard-dose group. Radiation dermatitis, diarrhea, and neutropenia were the most common grade ≥ 3 adverse events in both groups.
Most issues, such as general pain and anorectal-specific pain, resolved and returned to baseline levels by 6 weeks posttreatment in both groups; however, worse sexual function for both men and women was observed at 6 months following standard-dose therapy.
Compliance with radiotherapy and chemotherapy was higher in the reduced-dose group. Radiotherapy interruptions of 3 days or more occurred in 26% of patients in the standard-dose group and in 15% of those in the reduced-dose group. Chemotherapy modifications occurred in 49% of patients in the standard-dose group and in 37% of patients in the reduced-dose group.
IN PRACTICE:
'This reduced-dose regimen could be considered a new treatment option for frailer patients not fit for standard-dose chemoradiotherapy,' the authors wrote. '[The] 3-year locoregional failure rates are awaited.'
SOURCE:
This study, led by Alexandra Gilbert, FRCR, Leeds Institute of Medical Research at St. James's University Hospital, Leeds, England, and Richard Adams, FRCR, Centre for Trials Research, Cardiff University Heath Park, Cardiff, Wales, was published online in The Lancet Oncology .
LIMITATIONS:
Nonrandomized trial design prevented a formal comparison between treatment groups. The recruitment of participants with well-controlled HIV was lower than expected. Both groups used the same organ at risk dose constraints, potentially limiting the observation of differences in radiotherapy-related toxicity. Additionally, a formal prospective frailty assessment was not incorporated, with the study relying instead on age as a surrogate.
DISCLOSURES:
This study was funded by Cancer Research UK and Stand Up to Cancer. One author reported receiving support through a Cancer Research UK clinical trials fellowship. Another author reported receiving support from the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and three others reported receiving support from the National Institute for Health and Care Research Leeds Biomedical Research Centre.
