Impact of compliance to chemoradiation on long-term outcomes in squamous cell carcinoma of the anus: results of a post hoc analysis from the randomised phase III ACT II trial

Abstract

Background: Concurrent chemoradiation is standard-of-care for patients with squamous cell carcinoma of the anus. Poor compliance to chemotherapy, radiotherapy treatment interruptions and unplanned breaks may impact adversely on long-term outcomes.

Methods: The ACT II trial recruited 940 patients with localised squamous cell carcinoma of the anus, and assigned patients to mitomycin (week 1) or cisplatin (weeks 1 and 5), with fluorouracil (weeks 1 and 5) and radiotherapy (50.4 Gy in 28 fractions over 38 days). This post hoc analysis examined the association between baseline factors (age, gender, site, T stage and N stage), and compliance to treatment (radiotherapy and chemotherapy), and their effects on locoregional failure-free survival, progression-free survival (PFS) and overall survival (OS). Compliance was categorised into groups. Radiotherapy: six groups according to total dose and overall treatment time (OTT). Chemotherapy: three groups (A = per-protocol; B = dose reduction or delay; C = omitted).

Results: A total of 931/940 patients were assessable for radiotherapy and 936 for chemotherapy compliance. Baseline glomerular filtration rate <60 ml/min and cisplatin were significantly associated with poor week 5 compliance to chemotherapy (P = 0.003 and 0.02, respectively). Omission of week 5 chemotherapy was associated with significantly worse locoregional failure-free survival [hazard ratio (HR) 2.53 (1.33-4.82) P = 0.005]. Dose reductions/delays or omission of week 5 chemotherapy were associated with significantly worse PFS {HR: 1.56 [95% confidence interval (CI): 1.18-2.06], P = 0.002 and HR: 2.39 (95% CI: 1.44-3.98), P = 0.001, respectively} and OS [HR: 1.92 (95% CI: 1.41-2.63), P < 0.001 and HR: 2.88 (95% CI: 1.63-5.08), P < 0.001, respectively]. Receiving the target radiotherapy dose in >42 days is associated with worse PFS and OS [HR: 1.72 (95% CI: 1.17-2.54), P =0.006].

Conclusion: Poor compliance to chemotherapy and radiotherapy were associated with worse locoregional failure-free survival, PFS and OS. Treatment interruptions should be minimised, and OTT and total dose maintained.

Clinical trial number: ISRCTN 26715889.

Keywords: chemoradiation; chemotherapy; combined modality; compliance; radiotherapy; squamous cell carcinoma of the anus.