Fluorouracil-based neoadjuvant chemoradiotherapy with or without oxaliplatin for treatment of locally advanced rectal cancer: An updated systematic review and meta-analysis

Abstract

To measure the safety and efficacy of oxaliplatin (OX) application in neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC), EMBASE, PubMed, Cochrane Library, and Web of Science were used for a literature search. Cochrane's risk of bias tool of randomized controlled trials (RCTs) was used for quality evaluation. The statistical analyses were performed using RevMan 5.3. In addition, 95% confidence intervals (CIs) and pooled risk ratios (RRs) were calculated. Seven RCTs were included in our meta-analysis. After adding OX to fluoropyrimidine (FU), a marginal significant improvement in disease-free survival was noted compared with FU alone (RR = 0.89, 95% CI: 0.78–1.00; P = 0.05). Neoadjuvant CRT with OX significantly decreased the distant metastasis rate (RR = 0.79, 95% CI: 0.67–0.94, P = 0.007). However, no improvement in the local recurrence rate (RR = 0.86, 95% CI: 0.68–1.08; P = 0.19) was noted. In addition, neoadjuvant CRT with OX also significantly increased the pathologic complete response (RR = 1.24, 95% CI: 1.02–1.51; P = 0.03). Grade 3–4 acute toxicity and grade 3–4 diarrhea was considerably higher for OX/FU compared with FU alone. In conclusion, the use of OX on the basis of FU/capecitabine in preoperative CRT is feasible. LARC patients are likely to benefit from CRT regimens with OX.

What has preoperative radio(chemo)therapy brought to localized rectal cancer patients in terms of perioperative and long‐term outcomes over the past decades? A systematic review and meta‐analysis based on 41,121 patients

“…Therefore, simplified and optimized therapies which could maintain the present advantages of PRT/PCRT, further improve MFS and decrease adverse effects should be developed. Regarding metastases, the latest evidence suggests that adding oxaliplatin could significantly decrease the distant metastasis rate but may also increase acute III–IV toxicities in comparison with fluorouracil‐based neoadjuvant chemoradiotherapy . In addition, administering chemotherapy at an earlier point might decrease micrometastases and reduce the incidence of distant metastases .…”

“…Regarding metastases, the latest evidence suggests that adding oxaliplatin could significantly decrease the distant metastasis rate but may also increase acute III-IV toxicities in comparison with fluorouracil-based neoadjuvant chemoradiotherapy. 38 In addition, administering chemotherapy at an earlier point might decrease micrometastases and reduce the incidence of distant metastases. 39 Thus, induction chemotherapy followed by PCRT may achieve the full advantage of systemic chemotherapy.…”

S3-Leitlinie – Kolorektales Karzinom

“…In der deutschen CAO/ARO/AIO-04-Studie konnte ein signifikant verbessertes krankheitsfreies Überleben (als primärer Endpunkt) nachgewiesen werden; eine Metaanalyse unter Einschluss von 4 Studien mit Angaben zum krankheitsfreien Überleben beschrieb einen marginal signifikanten Effekt auf diesen Endpunkt (HR 0,89; 95 % CI, 0,78 -1,00, p = 0,05) [1009]. In fünf der sieben Einzelstudien konnte allerdings keine signifikante Verbesserung des krankheitsfreien Überlebens durch Inklusion von Oxaliplatin gezeigt werden, Langzeitergebnisse zur FOWARC-Studie stehen diesbezüglich noch aus.…”

Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer

“…5-Fluorouracil (5-FU) is currently used as the standard chemotherapy agent for nCRT of locally advanced rectal cancer while additional chemotherapy agents including capecitabine and oxaliplatin recently showed promise in increasing the pathologic complete response (pCR) compared with the regimen using 5-FU [8,9]. However, the response to nCRT in locally advanced rectal cancer varies among patients.…”