Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study

Bosset, Jean-François; Calais, G.; Mineur, Laurent; Maingon, P.; Stojanović-Rundić, Suzana; Bensadoun, René-Jean; Bardet, É.; Beny, Alexander; Ollier, Jean-Claude; Bolla, M.; Marchal, Dominique; Laethem, Jean‐Luc Van; Klein, V.; Giralt, Jordi; Clavère, P.; Glanzmann, Christoph; Cellier, P.; Collette, Laurence

doi:10.1016/s1470-2045(13)70599-0

Cited by 637 publications

(451 citation statements)

References 16 publications

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“…Auffallend ist in allen Studien insbesondere die schlechte Compliance bezüglich der adjuvanten Chemotherapie und die hohe Rate an Patienten (27 -28 %), die nach Operation keine adjuvante Behandlung erhalten konnten. Dies gilt insbesondere für Studien, bei denen die Randomisierung vor neoadjuvanter Behandlung und Operation erfolgte [959,1031]. Zwei der vier Studien mussten wegen schlechter Rekrutierung vorzeitig geschlossen werden und sind somit für die primären Endpunkte "underpowered" [1032,1033].…”

Section: Level Of Evidenceunclassified

“…Die Evidenz dieser retrospektiven Daten und Metaanalysen ist allerdings als niedrig zu bewerten und das Risiko für Verzerrungen hoch. Die 10-Jahres-Daten der randomisierten EORTC 22 921 bestätigten deren initiale Beobachtung jedenfalls nicht, dass insbesondere Patienten mit Downstaging (ypT0 -2) nach neoadjuvanter Therapie von der adjuvanten Chemotherapie profitieren [959].…”

Section: Level Of Evidenceunclassified

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S3-Leitlinie – Kolorektales Karzinom

Schmiegel

Buchberger

Follmann³

et al. 2017

Z Gastroenterol

136

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Section: Level Of Evidenceunclassified

S3-Leitlinie – Kolorektales Karzinom

Schmiegel

Buchberger

Follmann³

et al. 2017

Z Gastroenterol

136

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“…However, a more recent meta-analysis of four trials which included preoperative radiotherapy, questions the benefit of postoperative AC (HR for DFS 0·91, CI 0·77-1·07; p=0·230), although only 75 of 1196 patients included in the report had oxaliplatin in addition to a fluoropyrimidine. [41] Many individuals exhibit poor tolerance of this package of treatment due to morbidity from radiotherapy and pelvic surgery resulting in failure to start AC or dose reductions [42]. Of 506 rectal cancer patients due to receive AC post LCPCRT in one study, only 43% tolerated the full course and 27% never started treatment [4,42].…”

Section: Rationale For Neoadjuvant Chemotherapy In Rectal Cancermentioning

confidence: 99%

“…[41] Many individuals exhibit poor tolerance of this package of treatment due to morbidity from radiotherapy and pelvic surgery resulting in failure to start AC or dose reductions [42]. Of 506 rectal cancer patients due to receive AC post LCPCRT in one study, only 43% tolerated the full course and 27% never started treatment [4,42].…”

Section: Rationale For Neoadjuvant Chemotherapy In Rectal Cancermentioning

confidence: 99%

Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

Gollins

Sebag‐Montefiore

2016

Clinical Oncology

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Improved surgical technique plus selective pre-operative radiotherapy, has decreased rectal cancer pelvic local recurrence (LR) from historically 25%, down to approximately 5-10%. However, this improvement has not reduced distant metastatic relapse, the main cause of death and a key issue in rectal cancer management.The current standard is local pelvic treatment (surgery +/-pre-operative radiotherapy) followed by adjuvant chemotherapy (AC), depending on resection histology. For circumferential resection margin (CRM)-threatened cancer on baseline MRI, downstaging long-course pre-operative chemoradiation (LCPCRT) is generally used. However, for non-CRM threatened disease, varying approaches are currently adopted in the UK, including straight to surgery (STS), short-course pre-operative radiotherapy (SCPRT) and LCPCRT.Clinical trials are investigating intensification of concurrent chemoradiation. There is also increasing interest in investigating pre-operative neoadjuvant chemotherapy (NAC) as a way of exposing micro-metastatic disease to full dose systemic chemotherapy as early as possible and potentially reducing metastatic relapse.Phase II trials suggest that this strategy is feasible, with promising histological response and low rates of tumour progression during NAC. Phase III trials are needed to determine the benefit of NAC when added to standard therapy and also to determine if it can be used instead of neoadjuvant radiotherapy based schedules.

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“…Despite the widespread use of this approach, the evidence for beneficial effects of postoperative chemotherapy is conflicting. Indeed, the longterm results (10 years of followup) of the European Organisation for Research and Treatment of Cancer (EORTC) 22921 randomised trial published in 2014 showed no benefit of postoperative adjuvant chemotherapy after preoperative chemoradiotherapy prompting the authors to question the validity of current recommendations [10] . Whether or not postoperative chemotherapy should be given is an important clinical dilemma for healthcare professionals, as chemotherapy is associated with significant systemic toxicity, which may lead to diminished quality of life [11] .…”

Section: Introductionmentioning

confidence: 99%

Adjuvant chemotherapy for rectal cancer: Is it needed?

Milinis

Thornton

Montazeri

et al. 2015

WJCO

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Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies.

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Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study

Cited by 637 publications

References 16 publications

S3-Leitlinie – Kolorektales Karzinom

S3-Leitlinie – Kolorektales Karzinom

Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

Adjuvant chemotherapy for rectal cancer: Is it needed?

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