Combination chemotherapy versus single agent chemotherapy during preoperative chemoradiation for resectable rectal cancer

Resende, Heloisa Magda; Lustosa, Suzana Angélica Silva; Menandro, Vinícius; Novaes, Juliana; Matos, Délcio

doi:10.1002/14651858.cd008531

Cited by 4 publications

(6 citation statements)

References 20 publications

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“…Both previous meta-analyses that assessed rates of distant recurrence are in line with the current work demonstrating a statistically significant improvement for the platin-amplified chemoradiotherapy (45,47). Finally, all previous meta-analyses corroborate the findings of increased pathological complete response as well as increased toxicity for the experimental group (20,(45)(46)(47)(48). Looking at the individual trial level, only the CAO/ARO/AIO-04 trial achieved a statistically significant result in favor of the oxaliplatin group regarding any survival endpoint-in this particular case, disease-free survival (23).…”

Section: Reviewsupporting

confidence: 88%

“…In comparison to previous systematic reviews on this topic (20,(45)(46)(47)(48), the current work includes additional studies and long-term data from PETACC-6 (5-year survival) (23), FOWARC (3-year survival) (24), and ACCORD 12/0405 PRODIGE 2 (5-year survival) (36), which have not been considered in previous meta-analyses. Furthermore, some of the previous metaanalysis presented methodological flaws, for instance, time-toevent data were analyzed as dichotomous outcomes (45)(46)(47) instead of the generally recommended method by log hazard ratios and its standard error (25).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, integration of platinum agents into neoadjuvant chemoradiotherapy in stage II/III rectal cancer is a promising concept to improve oncologic outcome in these patients (19). Several randomized controlled trials (RCTs) and meta-analyses of these trials have demonstrated favorable short-term outcomes in terms of increased rates of pathological complete response, but this benefit is accompanied by enhanced acute toxicity (20). Therefore, current guidelines do not recommend the routine addition of platinum agents to neoadjuvant chemoradiotherapy (2).…”

mentioning

confidence: 99%

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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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Section: Reviewsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…The primary outcome evaluated was pathologic complete response, which may be considered a surrogate efficacy endpoint only, and previous research has shown that it does not reliably predict long-term outcome [29]. Furthermore, a recent Cochrane review also only evaluated short-term results of the same four trials and qualitatively analyzed the long-term results of one of the trials [30]. With the recent publication of 3-to 5-year overall and disease-free survival outcomes for several trials [14,26,27], a well-conducted systematic review and meta-analysis of the evidence, with survival as primary outcome, has the potential to change current treatment paradigms in Germany and internationally.…”

Section: Introductionmentioning

confidence: 99%

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)

et al. 2018

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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

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“…Thus, combination chemotherapy regimens have been tried, similar to those used in metastatic disease, such as the addition of oxaliplatin and irinotecan, in order to improve the prognosis of patients with rectal cancer. It is suggested that combination chemotherapy with oxaliplatin could improve local control of the tumor in patients with resectable rectal cancer, although this regimen also causes greater toxicity (4).…”

Section: Introductionmentioning

confidence: 99%

The value of oxaliplatin in the systemic treatment of locally advanced rectal cancer

Martín-Aragón

Serrano

Benedı́

et al. 2018

J. Gastrointest. Oncol.

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The contribution of adjuvant oxaliplatin in the oncological evolution shows a favorable effect of LRC, DMFS, DFS and OS in the subgroups of patients that exhibit elements of response to neoadjuvant oxaliplatin (categories TRG 3-4, and pN0, downstaging T, downstaging N). Therefore, this neoadjuvant response profile with oxaliplatin, measured with highly reliable methodology (validated microscopic pathological response scales), defines a population of oxaliplatin-sensitive patients who benefits significantly from the administration of adjuvant oxaliplatin in sufficient cumulative doses (more of 5 cycles).

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Combination chemotherapy versus single agent chemotherapy during preoperative chemoradiation for resectable rectal cancer

Cited by 4 publications

References 20 publications

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

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

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)

The value of oxaliplatin in the systemic treatment of locally advanced rectal cancer

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