Effect of Neoadjuvant Chemoradiotherapy with Capecitabine versus Fluorouracil for Locally Advanced Rectal Cancer: A Meta-Analysis

Liu, Guochen; Yan, Jun; He, Qing-Yu; An, Xin; Pan, Zhi Zhong; Ding, Pei Rong

doi:10.1155/2016/1798285

Cited by 12 publications

(8 citation statements)

References 25 publications

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“…In 2016, a meta-analysis compared 5FU and CAP as neoadjuvant CRT for locally advanced rectal cancer 28. The meta-analysis included two RCTs and seven retrospective studies, and showed that CAP was significantly more efficacious than 5FU.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemoradiation for locally advanced rectal cancer: a systematic review of the literature with network meta-analysis

Chen¹,

Chen²,

Xu³

et al. 2019

CMAR

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BackgroundNeoadjuvant chemoradiotherapy (CRT) prior to surgery is a standard therapy for locally advanced rectal cancer, but the optimum regime is not conclusive. This meta-analysis evaluated various CRT regimens with regard to the rate of pathologic complete response (pCR) and toxic effects of grade ≥3.MethodsThe databases PubMed, Cochrane Library, and Embase were searched for randomized controlled trials (RCTs) that compared neoadjuvant CRT regimes for treating patients with locally advanced rectal cancer, published before 28 December 2017. The primary end points were pCR and toxic effects. A network meta-analysis was applied.ResultsFourteen RCTs (with 5,599 participants) involving the following eight regimens were included: fluorouracil (5FU) alone, or 5FU with oxaliplatin (OXA), cisplatin, or irinotecan (CPT-11); capecitabine (CAP) alone, or CAP with OXA or CPT-11; and CPT-11 with combined tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. The rate of pCR associated with CAP + OXA was significantly higher compared with 5FU alone; there were no significant differences among the other regimens. The toxicity of 5FU + OXA or CAP + OXA was significantly worse than that of 5FU alone or CAP alone. CAP + OXA and CAP were ranked, respectively, the most and second most effective regimens in terms of pCR rate. 5FU alone and CAP alone likely had the lowest and second lowest toxicity, respectively.ConclusionAmong the currently available CRT regimens for locally advanced rectal cancer, this meta-analysis indicated that CAP + OXA provides the superior clinical results. Adding OXA to 5FU or CAP significantly increases toxicity.

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Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemoradiation for locally advanced rectal cancer: a systematic review of the literature with network meta-analysis

Chen¹,

Chen²,

Xu³

et al. 2019

CMAR

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“…Neoadjuvant chemoradiotherapy plays an indisputable role in minimising the aggressiveness of surgical procedures. Those methods result in significant downstaging of rectal tumours, including T4 cancer [ 32 , 33 ]. For ultralow cancer, neoadjuvant radiotherapy provides an additional benefit in extending the chance for sphincter-saving procedures [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

A quest for sphincter-saving surgery in ultralow rectal tumours—a single-centre cohort study

et al. 2018

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IntroductionDespite the progress in the treatment of colorectal cancer, there is still no optimal strategy for tumours located adjacent to the anal sphincter. This study aims to evaluate oncological and functional results of surgery for rectal cancer in unfavourable locations in proximity to anal sphincters.Materials and methodsPatients with rectal cancer, which was either initially infiltrating the anal sphincter or located in the close proximity of the sphincter, were included in the study. Patients were submitted to extralevator abdominoperineal resection (APR), intersphincteric resection, or transanal total mesorectal excision (TaTME). Primary outcomes were perioperative data: operative time, blood loss, complications, length of stay (LOS), and 30-day mortality. Secondary outcomes were pathological quality of the specimens and functional outcome 6 months after defunctioning ileostomy closure.ResultsAmong patients with cancer adjacent to the anal sphincter, 13 (25%) underwent APR, 14 (27%) patients were submitted to intersphincteric resection, and 25 (48%) patients were treated with the TaTME approach. Operative time was 240 (210–270 IQR) for APR, 212.5 (170–260 IQR) for intersphincteric resection, and 270 (240–330 IQR) for TaTME (p = 0.018). Perioperative morbidity was 31% for APR, 36% for intersphincteric resections, and 12% for the TaTME group (p = 0.181). Complete mesorectal excision was achieved in 92% of specimens in the TaTME group, 93% in intersphincteric resections, and 78% in the APR group (p = 0.72). Median circumferential resection margin in APR was 6 mm (4–7 IQR), in intersphincteric resections 7.5 mm (2.5–10 IQR), and in the TaTME group 4 mm (2.8–8 IQR). All patients after intersphincteric resections developed major low anterior resection syndrome (LARS). Four patients in the TaTME group developed minor LARS, and 21 had major LARS.ConclusionSphincter-saving rectal resections are a feasible alternative to APR with good clinical, pathological, and oncological outcomes. Intersphincteric resections and TaTME seem to be equal in terms of clinicopathological results. The functional outcome is yet to be investigated.Trial registrationThe study was retrospectively registered in Thai Clinical Trials Registry (23-07-2018, ID TCTR20180724001).

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“…In contrast to the findings of this subgroup analysis, NSABP R-04, the only trial that assessed both 5-FU vs capecitabine with or without oxaliplatin in a four-arm design, demonstrated similar effects for 5-year overall and disease-free survival for 5-FU vs capecitabine (41). On the other hand, a meta-analysis on 5-FU vs capecitabine (without oxaliplatin) during neoadjuvant chemoradiotherapy for locally advanced rectal cancer even demonstrated superiority of capecitabine compared to 5-FU (49). These contradictory results could also be explained in part by the differing treatment schedules of the CAO/ARO/AIO-04 trial, which led to the statistically significant result for the 5-FU subgroup in the subgroup analysis of disease-free survival (22) and the negative results of PETACC-6, which shift the result of the capecitabine subgroup to a lesser effect (24).…”

Section: Reviewmentioning

confidence: 97%

Addition of Platinum Derivatives to Fluoropyrimidine-Based Neoadjuvant Chemoradiotherapy for Stage II/III Rectal Cancer: Systematic Review and Meta-Analysis

Hüttner¹,

Probst²,

Kalkum³

et al. 2019

JNCI: Journal of the National Cancer Institute

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Background Current guidelines recommend neoadjuvant therapy for patients with stage II or III rectal cancer. The addition of platinum derivatives to fluoropyrimidine-based chemoradiotherapy has been frequently investigated, but their role in this setting remains controversial. Methods PubMed, Cochrane Library, and Web of Science were systematically searched for randomized trials comparing chemoradiotherapy with or without platinum agents in stage II or III rectal cancer. Main outcome parameters were overall and disease-free survival, additional outcomes included pathological complete response, isolated local recurrence, distant recurrence, toxicity, and perioperative morbidity. Time-to-event data were pooled as hazard ratios (HRs) by the inverse variance method and binary outcomes as odds ratios (ORs) by the Peto method with their respective 95% confidence interval (CI). All statistical tests were two-sided. Results Ten randomized controlled trials with data on 5599 patients were included in the meta-analysis. Platinum derivatives did not statistically significantly improve overall survival (HR = 0.93, 95% CI = 0.82 to 1.05, P = .23), disease-free survival (HR = 0.91, 95% CI = 0.83 to 1.01, P = .07), or local recurrence (OR = 0.83, 95% CI = 0.66 to 1.05, P = .12). However, it led to a statistically significant increase of pathological complete response (OR = 1.31, 95% CI = 1.10 to 1.55, P = .002) and a statistically significant reduction of distant recurrence (OR = 0.78, 95% CI = 0.66 to 0.92, P = .004). Benefits were accompanied by higher rates of grade 3 or 4 toxicities. Conclusions Intensified neoadjuvant chemoradiotherapy with the addition of platinum derivatives cannot be recommended routinely because it did not improve overall or disease-free survival and was associated with increased toxicity. It needs to be elucidated whether the benefits in distant recurrence and pathological complete response may be advantageous for selected high-risk patients.

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Effect of Neoadjuvant Chemoradiotherapy with Capecitabine versus Fluorouracil for Locally Advanced Rectal Cancer: A Meta-Analysis

Cited by 12 publications

References 25 publications

Neoadjuvant chemoradiation for locally advanced rectal cancer: a systematic review of the literature with network meta-analysis

Neoadjuvant chemoradiation for locally advanced rectal cancer: a systematic review of the literature with network meta-analysis

A quest for sphincter-saving surgery in ultralow rectal tumours—a single-centre cohort study

Addition of Platinum Derivatives to Fluoropyrimidine-Based Neoadjuvant Chemoradiotherapy for Stage II/III Rectal Cancer: Systematic Review and Meta-Analysis

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