Dataset Information

BACCHUS: A randomised non-comparative phase II study of neoadjuvant chemotherapy (NACT) in patients with locally advanced rectal cancer (LARC).

ABSTRACT: Background:Chemoradiation (CRT) or short-course radiotherapy (SCRT) are standard treatments for locally advanced rectal cancer (LARC). We evaluated the efficacy/safety of two neoadjuvant chemotherapy (NACT) regimens as an alternative prior to total mesorectal excision (TME). Methods/design:This multi-centre, phase II trial in patients with magnetic resonance imaging (MRI) defined high-risk LARC (>cT3b, cN2+ or extramural venous invasion) randomised patients (1:1) to FOLFOX + Bevacizumab (Arm 1) or FOLFOXIRI + bevacizumab (Arm 2) every 14 days for 6 cycles prior to surgery. Patients were withdrawn if positron emission tomography (PET) standardised uptake value (SUV) after 3 cycles failed to decrease by >30% or increased compared to baseline. Primary endpoint was pathological complete response rate (pCR). Secondary endpoints included adverse events (AE) and toxicity. Neoadjuvant rectal (NAR) scores based on "T" and "N" downstaging were calculated. Findings:Twenty patients aged 18-75 years were randomised. The trial stopped early because of poor accrual. Seventeen patients completed all 6 cycles of NACT. One stopped due to myocardial infarction, 1 poor response on PET (both received CRT) and 1 committed suicide. 11 patients had G3 AE, 1 G4 AE (neutropenia), and 1 G5 (suicide). pCR (the primary endpoint) was 0/10 for Arm 1 and 2/10 for Arm 2 i.e. 2/20 (10%) overall. Median NAR score was 14·9 with 5 (28%), 7 (39%), and 6 (33%) having low, intermediate, or high scores. Surgical morbidity was acceptable (1/18 wound infection, no anastomotic leak/pelvic sepsis/fistulae). The 24-month progression-free survival rate was 75% (95% CI: 60%-85%). Interpretation:The primary endpoint (pCR rate) was not met. However, FOLFOXIRI and bevacizumab achieved promising pCR rates, low NAR scores and was well-tolerated. This regimen is suitable for testing as the novel arm against current standards of SCRT and/or CRT in a future trial.

SUBMITTER: Glynne-Jones R

PROVIDER: S-EPMC6151852 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

BACCHUS: A randomised non-comparative phase II study of neoadjuvant chemotherapy (NACT) in patients with locally advanced rectal cancer (LARC).

Glynne-Jones R R Hall M R MR Lopes A A Pearce S S Goh V V Bosompem S S Bridgewater J J Chau I I Wasan H H Moran B B Melcher L L West N P NP Quirke P P Wong W-L WL Beare S S Hava N N Duggan M M Harrison M M

Heliyon 20180922 9

<h4>Background</h4>Chemoradiation (CRT) or short-course radiotherapy (SCRT) are standard treatments for locally advanced rectal cancer (LARC). We evaluated the efficacy/safety of two neoadjuvant chemotherapy (NACT) regimens as an alternative prior to total mesorectal excision (TME).<h4>Methods/design</h4>This multi-centre, phase II trial in patients with magnetic resonance imaging (MRI) defined high-risk LARC (>cT3b, cN2+ or extramural venous invasion) randomised patients (1:1) to FOLFOX + Bevac ...[more]

PMID: 30258994

Similar Datasets

Project description:IntroductionThe NICHE trial showed remarkable results of neoadjuvant immunotherapy in colorectal cancer patients with mismatch repair (MMR) deficiency (dMMR). However, rectal cancer patients with dMMR accounted for only 10% of case. The therapeutic effect is unsatisfactory in MMR-proficient patients. Oxaliplatin has been demonstrated to induce immunogenic cell death (ICD), which may improve the therapeutic effect of programmed cell death 1 blockade; however, a maximum tolerated dose is required to induce ICD. Arterial embolisation chemotherapy provides drugs locally and can easily reach the maximum tolerated dose, which could be a significant method for delivering chemotherapeutic agents. Therefore, we designed a multicenter, prospective, single-arm, phase II study.Methods and analysisFirst, recruited patients will receive neoadjuvant arterial embolisation chemotherapy (NAEC) with oxaliplatin 85 mg/m2 and 3 mg/m2. After 2 days, three cycles of immunotherapy with intravenous tislelizumab (200 mg/body, day 1) will be initiated at an interval of 3 weeks. From the second cycle of immunotherapy, the XELOX regimen will be added. 3 weeks after neoadjuvant therapy finished, the operation will be initiated. Neoadjuvant Arterial Embolization Chemotherapy Combined PD-1 Inhibitor for Locally Advanced Rectal Cancer (NECI) Study combined arterial embolisation chemotherapy, immunotherapy and systemic chemotherapy. Based on this combination therapy, the maximum tolerated dose could easily be reached, and ICD could be induced by oxaliplatin easily. To our knowledge, the NECI Study is the first multicenter, prospective, single-arm, phase II clinical trial to assess the efficacy and safety of NAEC combined with tislelizumab and systemic chemotherapy in locally advanced rectal cancer. This study is expected to provide a new neoadjuvant therapeutic regimen for locally advanced rectal cancer.Ethics and disseminationThe Human Research Ethics Committee of the Fourth Affiliated Hospital of Zhejiang University School of Medicine approved this study protocol. The results will be published in peer-reviewed journals and presented at appropriate conferences.Trial registration numberNCT05420584.

Project description:ImportanceTreatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases.ObjectiveTo compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC.Design, setting, and participantsA retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified.ExposuresOf the 811 patients, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT).Main outcomes and measuresTreatment and outcome data for the 2 cohorts were compared. Dosing and completion of prescribed chemotherapy were assessed on the subset of patients who received all therapy at MSK.ResultsOf the 628 patients overall, 373 (59%) were men and 255 (41%) were women, with a mean (SD) age of 56.7 (12.9) years. Of the 308 patients in the TNT cohort, 181 (49%) were men and 127 (49%) were women. Of the 320 patients in the chemoRT with planned adjuvant chemotherapy cohort, 192 (60%) were men and 128 (40%) were women. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with planned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort.Conclusions and relevanceOur findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation.

Dataset Information

BACCHUS: A randomised non-comparative phase II study of neoadjuvant chemotherapy (NACT) in patients with locally advanced rectal cancer (LARC).

Publications

BACCHUS: A randomised non-comparative phase II study of neoadjuvant chemotherapy (NACT) in patients with locally advanced rectal cancer (LARC).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets