Compliance and tolerability of short-course radiotherapy followed by preoperative chemotherapy and surgery for high-risk rectal cancer - Results of the international randomized RAPIDO-trial.
Chemotherapy
Multimodal treatment
Preoperative radiotherapy
Rectal cancer
Journal
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
12
09
2019
revised:
01
03
2020
accepted:
07
03
2020
pubmed:
3
4
2020
medline:
15
4
2021
entrez:
3
4
2020
Statut:
ppublish
Résumé
Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is widely accepted as the standard of care for high-risk rectal cancer. Adjuvant chemotherapy is advised in several international guidelines, although the survival benefit remains unclear and compliance is poor. The current multidisciplinary approach has led to major improvements in local control, yet the occurrence of distant metastases has not decreased accordingly. The combination of short-course radiotherapy (SCRT) and chemotherapy in the waiting period before surgery might have several benefits, including higher compliance, downstaging and better effect of systemic therapy. This is an investigator-initiated, international multicentre randomized phase III trial. High-risk rectal cancer patients were randomized to SCRT followed by chemotherapy (6 cycles CAPOX or alternatively 9 cycles FOLFOX4) and subsequent surgery, or long-course radiotherapy (25-28 × 2-1.8 Gy) with concomitant capecitabine followed by surgery and optional postoperative chemotherapy (8 cycles CAPOX or 12 cycles FOLFOX4) according to local institutions' policy. The primary endpoint is time to disease-related treatment failure. Here, we report the compliance, toxicity and postoperative complications in both study groups. Between June 2011 and June 2016, 920 patients were enrolled. Of these, 901 were evaluable (460 in the experimental arm and 441 in the standard arm). All patients in the experimental arm received 5 × 5 Gy radiotherapy, and 84% of all patients received at least 75% of the prescribed chemotherapy. In the standard arm, the compliance for CRT was 93% and 58% for postoperative chemotherapy. Toxicity ≥grade 3 occurred in 48% of patients in the experimental arm, compared to 25% of patients in the standard arm during preoperative treatment and 35% of patients during postoperative chemotherapy. No statistically significant differences in surgical procedures or postoperative complications were observed. High compliance (84%) of preoperative systemic treatment could be achieved with the experimental approach. Although considerable toxicity was observed during preoperative therapy, this did not lead to differences in surgical procedures or postoperative complications. Longer follow-up time is needed to assess the primary endpoint and related outcomes.
Sections du résumé
BACKGROUND
Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is widely accepted as the standard of care for high-risk rectal cancer. Adjuvant chemotherapy is advised in several international guidelines, although the survival benefit remains unclear and compliance is poor. The current multidisciplinary approach has led to major improvements in local control, yet the occurrence of distant metastases has not decreased accordingly. The combination of short-course radiotherapy (SCRT) and chemotherapy in the waiting period before surgery might have several benefits, including higher compliance, downstaging and better effect of systemic therapy.
METHODS
This is an investigator-initiated, international multicentre randomized phase III trial. High-risk rectal cancer patients were randomized to SCRT followed by chemotherapy (6 cycles CAPOX or alternatively 9 cycles FOLFOX4) and subsequent surgery, or long-course radiotherapy (25-28 × 2-1.8 Gy) with concomitant capecitabine followed by surgery and optional postoperative chemotherapy (8 cycles CAPOX or 12 cycles FOLFOX4) according to local institutions' policy. The primary endpoint is time to disease-related treatment failure. Here, we report the compliance, toxicity and postoperative complications in both study groups.
FINDINGS
Between June 2011 and June 2016, 920 patients were enrolled. Of these, 901 were evaluable (460 in the experimental arm and 441 in the standard arm). All patients in the experimental arm received 5 × 5 Gy radiotherapy, and 84% of all patients received at least 75% of the prescribed chemotherapy. In the standard arm, the compliance for CRT was 93% and 58% for postoperative chemotherapy. Toxicity ≥grade 3 occurred in 48% of patients in the experimental arm, compared to 25% of patients in the standard arm during preoperative treatment and 35% of patients during postoperative chemotherapy. No statistically significant differences in surgical procedures or postoperative complications were observed.
INTERPRETATION
High compliance (84%) of preoperative systemic treatment could be achieved with the experimental approach. Although considerable toxicity was observed during preoperative therapy, this did not lead to differences in surgical procedures or postoperative complications. Longer follow-up time is needed to assess the primary endpoint and related outcomes.
Identifiants
pubmed: 32240909
pii: S0167-8140(20)30120-1
doi: 10.1016/j.radonc.2020.03.011
pii:
doi:
Substances chimiques
Fluorouracil
U3P01618RT
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
75-83Commentaires et corrections
Type : ErratumIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.