Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial

Rödel, Claus; Liersch, Torsten; Becker, Heinz; Fietkau, Rainer; Hohenberger, Werner; Hothorn, Torsten; Graeven, Ullrich; Arnold, Dirk; Lang-Welzenbach, Marga; Raab, Hans-Rudolf; Sülberg, Heiko; Wittekind, Christian; Potapov, Sergej; Staib, Ludger; Hess, Clemens F.; Weigang-Köhler, K.; Grabenbauer, Gerhard G.; Hoffmanns, Hans; Lindemann, Fritz; Schlenska-Lange, Anke; Folprecht, Gunnar; Sauer, Rolf

doi:10.1016/s1470-2045(12)70187-0

Cited by 613 publications

(461 citation statements)

References 19 publications

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“…Toxicity was more commonly seen in FOLFOX group, however there was no difference in frequency of grade 3 and grade 4 events. Similar results were reported in the CAO/ARO/AIO04 trial, which showed significant increase in the proportion of patients achieving pathological complete response (17% vs 13%) and improved 3year disease survival [76] . In contrast, interim results of PETACC6 trial reported in a conference abstract did not show survival advantage in FOLFOX group [79] .…”

Section: Oxaliplatin-based Regimenssupporting

confidence: 87%

“…Based on these encouraging results, several trials were carried out to determine the benefits of oxaliplatin in addition to standard fluopyridinaminebased regimens in rectal cancer (ACCORD12/0405Prodige, CAO/ARO/AIO04, ADORE, STAR01, NSAPB R04, PETACC6) [7378] . While some studies reported significant improvement in pathological response and diseasefree survival [76,78] , others found no superiority of oxaliplatin, but instead an increased risk of acute toxicity [74,75,77,79] . Only four trials reported the data on survival.…”

Section: Oxaliplatin-based Regimensmentioning

confidence: 99%

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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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Section: Oxaliplatin-based Regimenssupporting

confidence: 87%

Section: Oxaliplatin-based Regimensmentioning

confidence: 99%

Adjuvant chemotherapy for rectal cancer: Is it needed?

Milinis

Thornton

Montazeri

et al. 2015

WJCO

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“…The NSABP-R04 trial (United States) 9,10) , the STAR-01 trial (Italy) 11) , the ACCORD 12 trial (France) 12) , the CAO/ARO/AIO-04 trial (Germany) 13) , the FOWARC trial (China) 14) , and others were all Phase III randomized comparative trials that compared 5FU monotherapy with regimens that also included oxaliplatin (Table 1). Unfortunately, however, most of these trials found that although there was no difference in response rate between the two groups, adverse events were significantly more common in patients who also received oxaliplatin.…”

Section: Efforts To Improve Combined Chemotherapymentioning

confidence: 99%

Recent advances in neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Kawai

Ishihara

Nozawa

et al. 2017

J Anus Rectum Colon

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Abstract:Preoperative chemoradiotherapy (CRT) has been actively used in Europe and the United States to treat advanced low rectal cancer, and provides excellent local control. In Japan, however, the standard treatment is lateral lymph node dissection, and to date CRT has not been actively used. In recent years, an increasing number of Japanese institutions have been using preoperative CRT to treat locally advanced rectal cancer. In this review, we describe the latest trends in CRT under five headings: short-course or long-course radiation, efforts to improve combined chemotherapy, the addition of preoperative adjuvant chemotherapy, the watch and wait strategy, and the significance of lateral lymph node dissection in patients receiving CRT.

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“…Thus, along with the attempt of improving survival, local tumor control has been an essential goal in the management of rectal cancer. Adjuvant radiotherapy (RT) with or without chemotherapy (ChT) reduced local recurrence and became a standard treatment in the 1980s [14], which was later on gradually replaced by preoperative RT (nRT) [9,45] or neoadjuvant radiochemotherapy (nRCT) [3,4,10,34,37]. Further substantial progress in terms of local recurrence reduction was achieved with the advent of quality-assured total mesorectal excision (TME; [15]).…”

Section: When Is the Local Recurrence Risk Low Enough To Refrain Frommentioning

confidence: 99%

“…Innovative techniques such as intensity-modulated (IMRT; [20]) and image-guided (IGRT; [13]) radiotherapy will further permit adverse effects to be minimized. Individual response and toxicity scores [47] may be another promising tool and new concepts for systemic treatment are warranted for patients at risk of distant metastases [6,33,34,46]. Doubtlessly, quality optimization of established procedures, such as high resolution MRI or TME in the mesorectal plane, should promptly be translated into clinical routine.…”

Section: Should the Level Of Evidence Be Neglected?mentioning

confidence: 99%

Rectal cancer

et al. 2013

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When is the local recurrence risk low enough to refrain from the aim to prevent it?Local recurrence (LR) of rectal cancer is a devastating incident for each affected individual [2,21]. Thus, along with the attempt of improving survival, local tumor control has been an essential goal in the management of rectal cancer. Adjuvant radiotherapy (RT) with or without chemotherapy (ChT) reduced local recurrence and became a standard treatment in the 1980s [14], which was later on gradually replaced by preoperative RT (nRT) [9,45] or neoadjuvant radiochemotherapy (nRCT) [3,4,10,34,37]. Further substantial progress in terms of local recurrence reduction was achieved with the advent of quality-assured total mesorectal excision (TME; [15]). The next step was the introduction of magnetic resonance imaging (MRI) as a routine preoperative staging tool [1] facilitating the visualization of the distance between tumor and mesorectal fascia. If this distance is ≥1 mm on MRI, a negative circumferential resection margin (CRM) is assumed, provided that total mesorectal excision surgery is performed adequately. A negative CRM (defined as ≥1 mm on pathological work-up) has consecutively been identified and validated as an important surrogate parameter to predict the individual LR risk [12]. Results of the MERCURY study group (Magnetic Resonance Imaging in Rectal Cancer European Equivalence Study) whose authors propagated and investigated MRI-based treatment for rectal cancer were encouraging [23,43] and promoted similar attempts in the German-speaking community such as the OCUM study (optimized surgery and MRI-based multimodal therapy of rectal cancer). Preliminary results were recently published [22,42] and are commented in this editorial.Altogether, 230 patients with rectal cancer clinically staged as cT2-4, any cN, cM0 were included in this observational study. The anticipated CRM assessed by MRI (mrCRM) was used as a decision tool for selecting patients (n=230) either to undergo primary surgery (n=134) or to receive nRCT (n=96). For the lower third of the rectum (defined as <6 cm from the anal verge, 37%), nRCT was performed in all cT3 and cT4 tumors, irrespective of the anticipated CRM status; tumors of the middle third (i.e., 6 to <12 cm) were treated by nRCT in case of positive mrCRM only. For the upper third (12-16 cm), the decision was left to the discretion of the treating center. Clinically positive lymph nodes did not influence the choice of therapy; in patients with pathologically positive lymph nodes, chemotherapy was offered according to the standard of the respective centers. Postoperative RCT was restricted to patients with an involved CRM (pCRM ≤1 mm) [42].The mrCRM was positive in 74/230 patients, 72 in the nRCT group and 2 of the patients selected for surgery alone. A pathologically positive CRM (pCRM) occurred in 5.7% of all patients (nCRT: 11%, primary surgery: 1.5%). Pathology revealed complete remission (ypT0N0) after nRCT in 15% of patients, a partial remission in 67%. Even in patients whose margins were involv...

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Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial

Cited by 613 publications

References 19 publications

Adjuvant chemotherapy for rectal cancer: Is it needed?

Adjuvant chemotherapy for rectal cancer: Is it needed?

Recent advances in neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Rectal cancer

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