Addition of platinum derivatives to neoadjuvant single-agent fluoropyrimidine chemoradiotherapy in patients with stage II/III rectal cancer: protocol for a systematic review and meta-analysis (PROSPERO CRD42017073064)

Abstract

Background: Neoadjuvant (chemo-)radiation has proven to improve local control compared to surgery alone, but this improvement did not translate into better overall or disease-specific survival. The addition of oxaliplatin to fluoropyrimidine-based neoadjuvant chemoradiotherapy holds the potential of positively affecting survival in this context since it has been proven effective in the palliative and adjuvant setting of colorectal cancer. Thus, the objective of this systematic review is to assess the efficacy, safety, and quality of life resulting from adding a platinum derivative to neoadjuvant single-agent fluoropyrimidine-based chemoradiotherapy in patients with Union for International Cancer Control stage II and III rectal cancer. Methods: MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials will be systematically searched to identify all randomized controlled trials comparing single-agent fluoropyrimidine-based chemoradiotherapy to combined neoadjuvant therapy including a platinum derivative. Predefined data on trial design, quality, patient characteristics, and endpoints will be extracted. Quality of included trials will be assessed according to the Cochrane Risk of Bias Tool, and the GRADE recommendations will be applied to judge the quality of the resulting evidence. The main outcome parameter will be survival, but also treatment toxicity, perioperative morbidity, and quality of life will be assessed. Discussion: The findings of this systematic review and meta-analysis will provide novel insights into the efficacy and safety of combined neoadjuvant chemoradiotherapy including a platinum derivative and may form a basis for future clinical decision-making, guideline evaluation, and research prioritization. Systematic review registration: PROSPERO CRD42017073064

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

“…All stages of the review process were performed in accordance with the recommendations of the Cochrane Collaboration (25), and the report was prepared according to the Preferred reporting items for systematic reviews and meta-analyses (PRISMA) -recommendations (26). This systematic review has been registered prospectively in PROSPERO (CRD42017073064), and the protocol has been published (27).…”

“…A systematic literature search in the electronic databases MEDLINE (via PubMed), Web of Science, and Cochrane Central Register of Controlled Trials was performed up to October 1, 2018 (28). The final PubMed search strategy is provided in the Supplementary Methods (available online) (27). No language or other restrictions were applied.…”

“…Any disagreement was resolved by discussion and consensus. The full selection process is described in the protocol publication (27). The trial selection process is documented by a PRISMA flow diagram giving specific reasons for exclusion of studies at each stage ( Figure 1).…”

Role of Oxaliplatin in the Neoadjuvant Concurrent Chemoradiotherapy in Locally Advanced Rectal Cancer: a Review of Evidence

“…In a meta-analysis published in 2019 by Hüttner et al, 35 after a review of 10 randomized trials and 5599 patients, there was no benefit for adding oxaliplatin in OS, DFS, or LRC. However, it led to a statistically significant increase in pathological complete response (OR = 1.31, 95% CI = 1.10-1.55, P = .002) and a statistically significant reduction in distant recurrence (OR = 0.78, 95% CI = 0.66-0.92, P = .004).…”