In a UK phase II trial (PLATO-ACT4) reported in The Lancet Oncology, Gilbert et al compared short-term response rates with standard- vs reduced-dose chemoradiotherapy in patients with localized squamous cell carcinoma of the anus.
Study Details
In the multicenter, open-label, noncomparative trial, 160 patients with early-stage disease (T1-2 [≤ 4 cm] N0-NxM0) were randomly assigned 2:1 between April 2017 and December 2020 to receive reduced-dose intensity-modulated radiotherapy (rd-IMRT) at 41.4 Gy in 23 fractions (n = 105) or standard-dose IMRT (sd-IMRT) at 50.4 Gy in 28 fractions (n = 55), both with concurrent mitomycin and capecitabine. The primary outcome measure of the study is 3-year locoregional failure rates; the current report analyzed secondary endpoints at 6 months after the end of treatment.
Patients had a median age of 66 years; 73% were female; and 129 (94%) of 138 evaluable samples were p16-positive.
Key Findings
Among evaluable patients, complete clinical response was present at 6 months after end of treatment in 92% (n = 89 of 97) of the rd-IMRT group and 87% (n = 46 of 53) of the sd-IMRT group.
Radiotherapy interruptions of 3 days or more occurred in 16 (15%) of 105 patients in the rd-IMRT group and 14 (26%) of 55 in the sd-IMRT group. Chemotherapy modifications occurred in 39 patients (37%) in the rd-IMRT group and 27 (49%) in the sd-IMRT group.
Grade ≥ 3 acute toxicity occurred in 35% of those in the rd-IMRT group and 46% of those in the sd-IMRT group, most commonly radiation dermatitis (10% vs 13%) and diarrhea (9% vs 7%). Serious adverse events occurred in 10% of the rd-IMRT group and 15% of the sd-IMRT group.
Patient-reported outcomes (assessed via the EORTC QLQ-C30 and ANL27) for most items had deteriorated by end of treatment, but resolved to baseline by 6 weeks after end of treatment in both groups. At 6 months after end of treatment, both male and female patients in the sd-IMRT group had poorer sexual function.
The investigators concluded: “Good 6-month complete clinical response rates were seen in both groups. Early results suggest rd-IMRT is well tolerated with oncological outcomes maintained. Three-year locoregional failure rates are awaited.”
Alexandra Gilbert, FRCR, of Leeds Institute of Medical Research at St James’s, University of Leeds, St James’s University Hospital, Leeds, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Cancer Research UK and Stand Up to Cancer. For full disclosures of all study authors, visit The Lancet Oncology.
