In a UK phase II trial (PLATO-ACT4) reported in The Lancet Oncology, Gilbert et al evaluated whether short-term results showed good complete response rates with both standard-dose and 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 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 is 3-year locoregional failure rates. The current report analyzes secondary endpoints at 6 months after the end of treatment.
Key Findings
Patients had a median age of 66 years, 73% were female, and 129 of 138 evaluable samples (94%) were human papillomavirus (HPV) p16–positive.
Among evaluable patients, complete clinical response was present at 6 months after the end of treatment in 92% (89/97) of the rd-IMRT group and 87% (46/53) of the sd-IMRT group.
Radiotherapy interruptions of 3 days or more occurred in 16 of 105 patients (15%) in the rd-IMRT group and 14 of 55 (26%) in the sd-IMRT group. Chemotherapy modifications occurred in 39 patients (37%) in the rd-IMRT group and 27 patients (49%) in the sd-IMRT group.
Grade ≥ 3 acute toxicity occurred in 35% of the rd-IMRT group and 46% of the sd-IMRT group, most commonly radiation dermatitis (10% and 13%) and diarrhea (9% and 7%). Serious adverse events were reported in 10% of the rd-IMRT group and 15% of the sd-IMRT group.
Patient-reported outcomes (EORTC QLQ-C30 and ANL27) for most items had deteriorated by the 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 responses rates were seen in both groups. Early results suggest rd-IMRT is well tolerated with oncological outcomes maintained. [The] 3-year locoregional failure rates are awaited.”
Alexandra Gilbert, FRCR, of the University of Leeds, St James’s University Hospital, Leeds, is the corresponding author of 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.
