Standard Versus Dose Reduced Chemoradiotherapy in Anal Cancer: Short Term Results of the PhaseII PLATO-ACT4 Randomised Controlled Trial (RCT) ISRCTN88455282.

Abstract

Background: Localised squamous cell carcinoma of the anus is treated with radical chemoradiotherapy. Cure rates are high, but treatment can result in significant acute and long-term morbidity. We aimed to determine whether lower dose chemoradiotherapy maintains high local control rates in patients with early-stage disease, with the secondary aim of reducing toxicity. Methods: ACT4 is a phase II prospective, multi-centre, two-arm non-comparative randomised controlled trial, investigating reduced dose intensity-modulated chemoradiotherapy (rd-IMRT: 41.4Gy in 23fractions) in patients with early-stage anal cancer; T1-2( Methods: ACT4 is a phase II prospective, multi-centre, two-arm non-comparative randomised controlled trial, investigating reduced dose intensity-modulated chemoradiotherapy (rd-IMRT: 41.4Gy in 23fractions) in patients with early-stage anal cancer; T1-2( Findings: 163 patients were recruited from 28 UK sites between 24/4/2017 and 1/12/2020. 160 were included in the primary analysis (sd-IMRT n=55; dr-IMRT n=105). Median age was 66years (35-87years); female 73.1% (117/160); p16 positive 93.5% (129/138). Complete clinical responses (CCR) at 6-months were 86.7% (46/53) sd-IMRT and 91.8% (89/97) rd-IMRT. Radiotherapy interruptions 3 days were 25.5% (14/55) sd-IMRT and 15.2% (16/105) rd-IMRT. Chemotherapy modifications were 49.1% (27/55) sd-IMRT and 37.1% (39/105) rd-IMRT. >=Grade 3 acute toxicity was reported in 45.5% (25/55) sd-IMRT and 35.2% (37/105) rd-IMRT. Patients >=70years treated with sd-IMRT experienced comparatively more treatment interruptions and worse acute toxicity than younger patients; rd-IMRT interruptions and toxicity were similar. Patient reported outcomes for most issues deteriorated at the end of treatment and resolved to baseline by 6-weeks in both arms. Poorer sexual function for men and women was observed at 6-months following sd-IMRT. Interpretation: Excellent 6-month CCR rates were seen in both arms. Treatment compliance was better using rd-IMRT with lower acute toxicity rates. Early results suggest rd-IMRT is better tolerated, particular in older patients, with oncological outcomes maintained. 3-year LRF rates are awaited.