Is there a benefit of oxaliplatin in neoadjuvant treatment of locally advanced rectal cancer? An updated meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4098-4098
Author(s):  
Gaetan Des Guetz ◽  
Thierry Landre ◽  
Anne Larrouy ◽  
Yves Panis ◽  
Jean F. Morere ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Trials ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Cochrane Library ◽  
Perioperative Chemotherapy ◽  
Grade 3

4098 Background: Neoadjuvant fluoropyrimidine (5FU or capecitabine)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is still unclear. Methods: To identify clinical trials combining oxaliplatin in preoperative CRT or perioperative chemotherapy for LARC published until December 2019, we searched PubMed, the Cochrane Library. We also search for relevant ASCO conferences. Primary endpoint was Disease-Free-Survival (DFS). Data were extracted from every study to perform a meta-analysis using Review Manager (version 5.3). Results: A total of 7 Randomized Clinical Trials (ACCORD-12, CARO-AIO-04, FOWARC, JIAO, NSABP, PETACC-6 and STAR-01) with 5782 stage II or III rectal cancer patients were analysed, including 2727 patients with OXP + 5FU regimen and 3055 patients with 5FU alone regimen. Compared with 5FU-based regimen group, OXP-based regimen group improved DFS (HR = 0.90, 95% CI: 0.81−0.99, P = 0.03) and increased pathologic Complete Response (OR = 1.21, 95% CI: 1.07−1.37, P = 0.002). Patients treated with OXP-regimen had significantly less metastatic disease (OR = 0.79; 95% CI, 0.67 to 0.94; p = 0.007). Considering Adverse Events (AEs), there was more grade 3-4 diarrhoea with OXP (OR = 2.41, 95% CI: 1.74−3.32, P < 0.00001). However, there were no significant differences grade 3-4 haematologic AEs (OR = 1.16, 95% CI: 0.87−1.57, P = 0.31). Conclusions: Combining oxaliplatin with capecitabine or 5FU in preoperative chemoradiotherapy or perioperative chemotherapy seems beneficial significantly and improved DFS. It remains necessary to identify which patients benefit most from the addition of oxaliplatin.

scholarly journals Is There a Benefit of Oxaliplatin in Combination with Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer? An Updated Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6035
Author(s):  
Gaëtan Des Guetz ◽  
Thierry Landre ◽  
Marc A. Bollet ◽  
Muriel Mathonnet ◽  
Laurent Quéro
Keyword(s):  
Rectal Cancer ◽  
Clinical Trials ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Long Term Results ◽  
Cochrane Library ◽  
Metastatic Progression ◽  
Grade 3

Background: Neoadjuvant fluoropyrimidine (5FU or capecitabine)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is still unclear. Methods: To identify clinical trials combining oxaliplatin in preoperative CRT or perioperative chemotherapy for LARC published until March 2021, we searched PubMed and the Cochrane Library. We also searched for relevant ASCO conference abstracts. The primary endpoint was disease-free survival (DFS). Data were extracted from every study to perform a meta-analysis using Review Manager (version 5.3). Results: A total of seven randomized clinical trials (ACCORD-12, CARO-AIO-04, FOWARC, JIAO, NSABP, PETACC-6, and STAR-01) with 5782 stage II or III rectal cancer patients were analyzed, including 2727 patients with OXP + 5FU regimen and 3055 patients with 5FU alone. Compared with the 5FU alone group, the OXP + 5FU regimen improved DFS (HR = 0.90, 95% CI: 0.81–0.99, p = 0.03) and pathologic complete response (pCR) (OR = 1.21, 95% CI: 1.07–1.37, p = 0.002). Patients treated with the OXP + 5FU regimen had significantly less metastatic progression (OR = 0.79; 95% CI, 0.67 to 0.94; p = 0.007). Considering adverse events (AEs), there was more grade 3–4 diarrhea with OXP + 5FU (OR = 2.41, 95% CI: 1.74–3.32, p < 0.00001). However, there were no significant differences grade 3–4 hematologic AEs (OR = 1.16, 95% CI: 0.87–1.57, p = 0.31). Conclusions: Our meta-analysis with long-term results from the randomized studies showed a benefit of the addition of OXP + 5FU regiment in terms of DFS, metastatic progression, and pCR rate that did not translate to improved OS.

Phase Ib/II study of neoadjuvant chemoradiotherapy with CRLX101 and capecitabine for locally advanced rectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15144-e15144 ◽  
Author(s):  
Andrew Wang ◽  
Autumn Jackson McRee ◽  
A. William Blackstock ◽  
Bert H. O'Neil ◽  
Dominic T. Moore ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib ◽  
Grade 3

e15144 Background: There is strong interest in the development of novel agents to further improve the therapeutic ratio of neoadjuvant chemoradiotherapy for rectal cancer. CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. The purpose of this Phase Ib/II study is to assess toxicity and to evaluate whether the addition of CRLX101 to chemoradiotherapy can improve pathologic complete response (pCR) for rectal cancer. Methods: This is a single-arm multicenter Phase Ib/II study examining the addition of CRLX101 to a standard capecitabine-based chemoradiotherapy regimen. Phase Ib employs a 3+3 dose escalation design with starting dose of 12 mg/m2 every other week (QOW). Dose level +1 was 15 mg/m2 (MTD for CRLX101 single agent QOW). Upon reaching MTD for QOW dosing, protocol was modified to evaluate QW CRLX101 dosing starting at 12 mg/m2 and 15 mg/m2as +1 level. Secondary endpoints included pCR and clinical outcome. Results: A total of 32 patients were enrolled on the trial. 26/32 had T3-4, 9/32 had N2 and 16/32 had N1 disease. For QOW dosing, 9 patients completed treatment without DLT and MTD was identified as 15 mg/m2 QOW. 14 patients were treated on the Phase II portion of the study at 15 mg/m2 QOW prior to the initiation of weekly dosing Phase Ib cohorts. For QW dosing, 0/3 patients experienced DLT at 12 mg/m2 and 1/6 patients experienced DLT at 15 mg/m2. The DLT was skin desquamation requiring treatment delay. QW MTD was identified as 15 mg/m2. Toxicities (all grade 3 except lymphopenia) that could possibly be attributed to CRLX101 are in Table 1. Full clinical and pathologic staging were available for 29/32 patients. Mean neoadjuvant rectal (NAR) score was 19 with standard deviation of 15. At the weekly MTD, 3/6 patients had pCR. Conclusions: CRLX101 weekly at 15 mg/m2+ standard capecitabine-based chemoradiotherapy appears to be well tolerated, with promising pCR rates that warrants further evaluation. A larger PhII trial should be considered with this regimen. Clinical trial information: NCT02010567. [Table: see text]

scholarly journals Adjuvant Second-Dose Chemotherapy before Surgery for Patients with Locally Advanced Rectal Malignancy Is Not Beneficial: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Min Chen ◽  
Xue Song ◽  
Liang-zhou Chen ◽  
Lin Xu ◽  
Yi-pu Lu ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Combination Chemotherapy ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Cochrane Library ◽  
Controlled Trials

Background. Preoperative chemoradiotherapy is the standard treatment for patients with locally advanced rectal cancer, although tumor responses vary widely; some patients may achieve a pathologic complete response rate (pCR) after chemoradiotherapy. Controversy exists with regard to the efficacy of different preoperative combination chemotherapy regimens and neoadjuvant chemoradiotherapy, compared with chemoradiotherapy alone. Methods. PubMed, the Cochrane Library, and Embase databases were searched for comparative studies of patients with locally advanced rectal cancer that were published between January 1991 and January 2016. Efficacies of different preoperative combination chemotherapy regimens and neoadjuvant chemoradiotherapy (group A) were compared with chemoradiotherapy alone (group B) in a meta-analysis using Review Manager v5.2. Results. Three prospective randomized controlled trials and two prospective nonrandomized controlled trials comprising 444 cases were eligible for analysis. No significant difference was detected in the rate of pCR (50/223, 22.4% versus 35/223, 15.7%; relative risk, RR: 1.42 [95% confidence interval, CI: 0.97–2.09], p=0.07) between the two groups. The rate of tumor regression was similar for both groups (122/203, 60.1% versus 111/203, 54.7%; RR: 1.11 [95% CI: 0.94–1.29], p=0.22). Conclusions. Adjuvant chemotherapy with preoperative chemoradiotherapy did not significantly improve the rate of pCR nor the rate of T and N downstaging.

Utility of restaging patients with stage II/III rectal cancer following neoadjuvant chemo/XRT: A systematic review.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 495-495
Author(s):  
Leah E. Hendrick ◽  
Renee L Levesque ◽  
David Shibata ◽  
Nathan M Hinkle ◽  
Justin J Monroe ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Treatment Plan ◽  
Meta Analysis ◽  
Systemic Disease ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Stage Ii ◽  
Cochrane Library

495 Background: In the US, patients with clinical stage II/III rectal cancer typically receive neoadjuvant chemoradiation (chemo/XRT) over 5-6 weeks followed by a 6-10 week break before proctectomy. As this chemotherapy is delivered at radio-sensitizing doses, there is essentially a 3-month window during which potential systemic disease is untreated. Evidence regarding the utility of restaging patients prior to proctectomy is limited. Methods: PubMed, Scopus, Web of Science, and the Cochrane Library were searched for studies evaluating the utility of restaging patients with locally advanced rectal cancer after completion of long course chemo/XRT, and reporting changes in management after restaging. Studies that were non-English, included < 50 patients, or examining the diagnostic accuracy of specific imaging modalities were excluded. Study quality was evaluated using the modified Newcastle Ottawa Scale. Results: Eight studies were identified including a total of 1251 patients restaged between completion of chemo/XRT and proctectomy. All studies were retrospective (6 single institution, 2 multi-institution). Restaging identified new metastatic disease in 72 (6.0%) patients, with 4 studies reporting specific sites: liver (n = 28), lung (n = 8), adrenal (n = 1), bone (n = 1), and multiple sites (n = 7). Overall, progression (distant or local) was detected in 85 (6.8%) patients and resulted in a reported change in management in 71 (5.7%) patients. One study identified an association of high-grade tumors with progression (p ≤ 0.05), however, this was not reported in any other study. Moreover, tumor-related prognostic characteristics were inconsistently reported among studies, precluding meta-analysis. Conclusions: Although restaging between completion of neoadjuvant chemo/XRT and proctectomy detects disease progression in only a small percentage of patients, findings may alter the treatment plan. A multi-institutional collaboration with analysis of well-defined prognostic variables may better identify a group of patients most likely to benefit from restaging.

Neoadjuvant chemoradiation for locally advanced rectal cancer with fluoropyrimidine alone or intensified with oxaliplatin: A systematic review and meta-analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 678-678 ◽  
Author(s):  
Ashlie Nadler ◽  
Elizabeth Handorf ◽  
Elin R. Sigurdson ◽  
Joshua E. Meyer ◽  
Crystal Shereen Denlinger ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Resection Margin ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Significant Heterogeneity ◽  
Short Term ◽  
Grade 3

678 Background: Improved outcomes have been demonstrated with the use of neoadjuvant fluoropyrimidine-based chemoradiotherapy and total mesorectal excision for locally advanced rectal cancer. The addition of oxaliplatin in the adjuvant setting has also resulted in improved disease-free survival (DFS). A meta-analysis was performed to evaluate DFS and overall survival (OS) with the addition of oxaliplatin to standard neoadjuvant chemoradiation for locally advanced rectal cancer. Methods: A systematic literature review was performed. Randomized-controlled trials (RCTs) comparing the addition of oxaliplatin in the neoadjuvant setting (oxaliplatin group) to fluoropyrimidine-based chemoradiation (standard group) were included. The primary outcomes were DFS and OS; secondary outcomes were short-term surgical results, morbidity, and mortality. Results were combined using meta-analysis via linear mixed-effects models. Calculations were performed using R. Results: Of 73 studies identified, 4 reported DFS (n=3829) and 3 reported OS (n=2680). There was no difference in DFS between the standard and oxaliplatin groups amongst RCTs [HR 0.90 (0.64-1.26), p=0.5313]. There was no difference in OS [HR 0.93 (0.59-1.47), p=0.9894]. There was no significant heterogeneity between RCTs for primary outcomes. There was also no difference in pathologic complete response rate [OR 0.93 (0.77-1.14), p=0.4923), resection margin (R0) status [OR 1.01 (0.59-1.72), p=0.9846], circumferential resection margin status [OR 0.84 (0.50-1.41), p=0.5079], sphincter saving surgery rate [OR 0.87 (0.74-1.03), p=0.1103], grade 3-4 toxicity [OR 1.60 (0.88-2.92), p=0.1251], and 60-day mortality [OR 1.27 (0.50-3.25), p=0.6148]. There was significant heterogeneity between RCTs for R0 status, circumferential margin status, and grade 3-4 toxicity. Adjuvant treatment varied across studies. Conclusions: There are no short-term or long-term survival benefits with the addition of oxaliplatin to fluoropyrimidine-based chemoradiation in the neoadjuvant setting for locally advanced rectal cancer.

Total neoadjuvant therapy compared with standard therapy in locally advanced rectal cancer: A systematic review and meta-analysis.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 709-709 ◽  
Author(s):  
Sashidhar Manthravadi ◽  
Weijing Sun ◽  
Anwaar Saeed ◽  
Joaquina Celebre Baranda ◽  
Anup Kasi
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Standard Therapy ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Total Neoadjuvant Therapy

709 Background: Standard therapy of locally advanced rectal cancer (LARC) includes concurrent chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy (CT). An alternative strategy known as Total Neoadjuvant Therapy (TNT) involves administration of CRT and CT prior to surgery with the goal of delivering uninterrupted systemic therapy to eradicate micrometastases. A comparison of these two approaches has not been reviewed previously. Methods: Following PRISMA guidelines, a systematic review of PubMed and Web of Science was performed from inception through September 2018 to identify studies which compared TNT with CRT in LARC. The outcomes of interest were pathologic complete response rates (PCR), sphincter-preserving surgery rates, ileostomy rates, disease-free survival (DFS) and overall survival (OS). Summary hazard ratios (HR) with 95% confidence intervals (CI) were estimated using a random effects model and heterogeneity was estimated using the inconsistency index (I2). Results: After reviewing 2,163 reports, 5 studies which compared CRT and TNT were selected for inclusion. These were reported from Europe and the United States and included a total of 1,134 patients of whom 552 received TNT. The pooled prevalence of PCR was 32.4% (range 17-28%) in the TNT group and 22.3% (range 4-21%) in the CRT group. In a meta-analysis of five studies, TNT was associated with a higher chance of achieving a pathologic complete response (OR 1.92; 95% CI 1.44- 2.57, I2= 22%). Recipients of TNT also had higher odds of receiving sphincter-sparing surgery (5 studies, OR 1.92; 95% CI 1.44- 2.57, I2= 0%) and lower odds of requiring an ileostomy (2 studies, OR 0.72; 95% CI 0.54- 0.96, I2= 0%). Only one study presented data on DFS and noted improved DFS in patients who received TNT (OR 0.72; 95% CI 0.54- 0.96). The impact of TNT relative to standard therapy on overall survival was not reported. Conclusions: Total Neoadjuvant Therapy is a promising strategy in locally advanced rectal cancer, with superior PCR rates compared to standard therapy. However, the long term impact on disease recurrence and overall survival remain unclear. These are best be studied in a prospective randomized clinical trial.

scholarly journals Mutational and Clinical Predictors of Pathologic Complete Response in the Treatment of Locally Advanced Rectal Cancer

2013 ◽  
Vol 45 (1) ◽  
pp. 34-39 ◽  
Author(s):  
Andrea L. Russo ◽  
David P. Ryan ◽  
Darrell R. Borger ◽  
Jennifer Y. Wo ◽  
Jackie Szymonifka ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Clinical Predictors
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