scholarly journals Randomized phase II study comparing the efficacy and safety of SOX versus mFOLFOX6 as neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer (KSCC1301)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keisuke Miwa ◽  
Eiji Oki ◽  
Masanobu Enomoto ◽  
Keisuke Ihara ◽  
Koji Ando ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Completion Rate ◽  
Rank Test ◽  
Current Standard

Abstract Background Preoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT. Methods Patients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety. Results From September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9–83.6) and 73.4% (95% CI 58.7–83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414–1.578). The 3-year survival rates were 92.3 and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5 and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable. Conclusion We demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases. Trial registration Date of enrolment of the first participant to the trial: 3rd Oct 2013; This study was registered in the UMIN clinical trials registry on 14th Aug, 2013. (Prospectively registered, UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J

scholarly journals Randomized Phase II Study Comparing the Efficacy and Safety of SOX versus mFOLFOX6 as Neoadjuvant Chemotherapy without Radiotherapy for Locally Advanced Rectal Cancer (KSCC1301)

2020 ◽  
Author(s):  
Keisuke Miwa ◽  
Eiji Oki ◽  
Masanobu Enomoto ◽  
Keisuke Ihara ◽  
Koji Ando ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Completion Rate ◽  
Rank Test ◽  
Current Standard

Abstract BackgroundPreoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT. MethodsPatients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety.ResultsFrom September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9–83.6) and 73.4% (95% CI 58.7–83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414–1.578). The 3-year survival rates were 92.3% and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5% and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable. ConclusionWe demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases.Trial registrationThis study was registered in the UMIN clinical trials registry on Aug 14th, 2013. (UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J

scholarly journals Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1539
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Bianca de Cássia Troncarelli Flores ◽  
Alexcia Camila Braun ◽  
Daniela de Jesus Ferreira Costa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Transforming Growth Factor ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

The prognosis valve of tumor regression grade in the same ypStage patients after neoadjuvant treatment in locally advanced rectal cancer: Post-hoc analysis of a prospective trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16129-e16129
Author(s):  
Jianwei Zhang ◽  
Yue Cai ◽  
Huabin Hu ◽  
Zehua Wu ◽  
Xiaoyu Xie ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Prospective Trial ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumor Regression Grade ◽  
Prognosis Factor

e16129 Background: The ypStage after neoadjuvant treatment was an important prognosis factor in locally advanced rectal cancer (LARC). pCR or ypStage 0 showed best prognosis, while ypStage II-III showed poor prognosis and further adjuvant chemotherapy with FOLFOX was recommended. Tumor regression grade (TRG) was another factor to evaluate the response to neoadjuvant treatment. Even in the same ypStage, the TRG could be different. Here, we tried to analyze the prognosis valve of TRG in the same ypStage after neoadjuvant treatment in LARC from a prospective trial (FOWARC study). Methods: Patients with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil plus radiotherapy followed by surgery and seven cycles of infusional fluorouracil as adjuvant treatment, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). Survival analysis was performed on different ypStage and TRG (WHO classification) group. Results: In total, 495 patients were randomly assigned to different neoadjuvant treatment. 444 patients received surgery with a median follow-up of 45.2 months. The 3-year disease free survival (DFS) in ypStage 0, ypStage I, ypStage II and ypStage III was 95.8%, 89.2%, 71.7% and 55.1%, respectively (P < 0.0001). In TRG 0, 1, 2 and 3, the 3-year DFS was 93.3%, 83.2%, 68.4% and 63.6%, respectively (P < 0.0001). In ypStage I subgroup, TRG was not an independent prognosis factor, the 3-year DFS for TRG 1, 2 and 3 was 90.0%, 90.7% and 76.2%, respectively (P = 0.277). In ypStage II population, the 3-year DFS for TRG 1, 2 and 3 was 78.6%, 70.3% and 64.7%, respectively (P = 0.184). The ypStage III group showed great heterogeneity, the 3-year DFS for TRG 0-3 was 60.0%, 70.0%, 41.8% and 59.5%, respectively (P = 0.067). Conclusions: Both ypStage and TRG was strong prognosis factor for rectal cancer after neoadjuvant treatment. However, TRG was not an independent prognosis factor in the same ypStage after neoadjuvant treatment. Clinical trial information: NCT01211210 .

scholarly journals Small Intestinal Perforation During Neoadjuvant Chemotherapy for Locally Advanced Rectal Cancer: A Case Report

2020 ◽  
Author(s):  
Zechuan Jin ◽  
Du He ◽  
Yu Shen ◽  
Xiangbing Deng ◽  
Ziqiang Wang
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Intestinal Perforation ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Gastrointestinal Symptoms ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Pathological Examination ◽  
Small Intestinal

Abstract Background: For patients with locally advanced rectal cancer, side effects such as nausea, vomiting and loss of appetite may occur during neoadjuvant chemotherapy, but small intestinal perforation is very rare.Case presentation: We present a case of a 62-year-old man who suffered small intestinal perforation in the first cycle neoadjuvant treatment of locally advanced rectal cancer with capecitabine and oxaliplatin. Six days after the start of neoadjuvant chemotherapy, he began to develop intermittent abdominal pain, accompanied by diarrhea and abdominal distension. The CT scan revealed an abscess with free air in the pelvic cavity with proximal intestinal ileus. Then we performed a laparotomy. After enterolysis, the rectum with tumor was carefully examined with no perforative lesion, and the terminal ileum about 15cm from the ileocecum which adhere to the pelvic abscess had one about 0.8cm ulcer. The patient had a radical anterior resection and the morbid small bowel resection with protective ileostomy. The postoperative pathological examination showed the full-thickness necrosis of the intestinal wall in the ileal lesion with peripheral acute suppurative inflammation. AND the final pathological stage of the tumor was pT3N0M0 (American Joint Committee on Cancer, eighth edition).Conclusion: As a chemotherapy regimen based on fluorouracil and oxaliplatin, small intestinal perforation is a very rare complication. The most common complications of these two drugs are gastrointestinal symptoms such as diarrhea. Therefore, when the complications are not relieved during chemotherapy, we should think of a more serious possibility.

The efficacy of neoadjuvant treatment in locally advanced rectal cancer with dMMR.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 615-615 ◽  
Author(s):  
Yanhong Deng ◽  
Jianwei Zhang
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Group A ◽  
Tumor Downstaging ◽  
Group B ◽  
Group D

615 Background: The incidence of Mismatch repair gene deficiency (dMMR) was about 15% in colorectal cancer, but mostly in right side colon cancer, while in locally advanced rectal cancer, it is very rare. As is known, adjuvant chemotherapy with 5FU alone was not recommended in stage II colon cancer with dMMR or MSI. However, in locally advanced rectal cancer with dMMR or MSI, the efficacy of neoadjuvant treatment with 5FU was not yet known. Methods: We enrolled patients with locally advanced rectal cancer from three prospective clinical trials, including the FOWARC study (N = 309), the mFOLFOXIRI neoadjuvant chemotherapy trial (N = 106) and the total neoadjuvant treatment with FOLFOX and radiotherapy (N = 129). From the 544 patients, 35 (6.4%) patients were dMMR, 133 patients with unknown status of MMR. Among the 35 patients, 10 patients received 5FU concurrent with radiotherapy (group A), nine patients underwent FOLFOX concurrent with radiation (group B), and 12 patients received FOLFOX neoadjuvant chemotherapy alone (group C). Another four patients underwent mFOLFOXIRI neoadjuvant chemotherapy alone (group D), including one patient with nivolumab as neoadjuvant treatment after chemotherapy. Results: Totally, 4 (11.4%) patients achieved pathologic complete response, and 13 (37%) patients had tumor downstaging to ypT0-2N0M0 (stage 0-I). In group A, the pCR rate was 10% (1/10), the tumor downstaging rate was 20% (2/10); In group B, the pCR rate was 33.3% (3/9), the tumor downstaging rate was 55.6% (5/9); In group C, the tumor downstaging rate was 41.7% (5/12). In group D, only one patient achieved pCR, and it is the one who received nivolumab as neoadjuvant treatment. Conclusions: The efficacy of neoadjuvant in locally advanced rectal cancer seemed not affected by the MMR status. But further study was needed.

Emerging strategies in the initial management of locally advanced rectal cancer

2019 ◽  
Vol 15 (25) ◽  
pp. 2955-2965 ◽  
Author(s):  
Lucy Gately ◽  
Hui-Li Wong ◽  
Jeanne Tie ◽  
Rachel Wong ◽  
Margaret Lee ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Treatment Plan ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Current Standard ◽  
Initial Management

The initial management of locally advanced rectal cancer continues to evolve and formulating the ideal treatment plan remains challenging, with a multitude of emerging treatment strategies and either limited or inconsistent data to support these. The main objective of neoadjuvant treatment is to maximize disease control and minimize toxicity and impact on quality of life. Ultimately, the optimal approach needs to be personalized to the individual. In this Review, we discuss the various strategies currently used and being further investigated in the initial treatment of patients presenting with locally advanced rectal cancer. We describe the evidence behind the current standard of care recommendations and emerging new options, as well as potential biomarkers that may assist with further refining treatment selection.

Preliminary results of the organ preservation of rectal adenocarcinoma (OPRA) trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4008-4008 ◽  
Author(s):  
Julio Garcia-Aguilar ◽  
Sujata Patil ◽  
Jin K. Kim ◽  
Jonathan B. Yuval ◽  
Hannah Thompson ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Organ Preservation ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Rank Test ◽  
Type I ◽  
Free Survival

4008 Background: Organ preservation (OP) with a watch and wait strategy (WW) and total neoadjuvant therapy (TNT) are new treatment paradigms for patients with locally advanced rectal cancer. The safety and efficacy of WW and of TNT have not been studied prospectively. Methods: Patients with MRI stage II and III rectal adenocarcinoma were randomized to 4 months of FOLFOX or CAPEOX before (Induction) or after (Consolidation) fluorouracil or capecitabine based chemoradiotherapy (CRT). Patients were re-staged 8-12 weeks after finishing TNT with digital rectal exam, flexible sigmoidoscopy and MRI. Patients with complete or near-complete clinical response were offered WW. Those with incomplete response had total mesorectal excision. The trial was designed so that each arm served as its own single-stage study that discriminates between 3-year disease-free survival (DFS) rates of 75% (historical null) and 85%, with 86% power, and a two-sided type I error of 5%. Secondary objectives included comparing DFS, OP, and distant metastasis-free survival (DMFS) rates between the two arms using the log-rank test. Results: Of 324 patients enrolled, 307 (152 I, 155 C) are currently evaluable for the time-to-event analysis as of 2/1/2020. Median follow-up is 2.1 years; 52 DFS events were observed. Patient demographics and tumor characteristics were generally balanced across the two arms. Full compliance with systemic chemotherapy was 82% and 81% for the I- and C-arms, respectively. The median radiation dose was 5400 cGy for both arms. Table shows 3-y DFS, DMFS, and OP rates. Conclusions: A WW strategy for patients with locally advanced rectal cancer that achieve a clinical complete response to TNT results in organ preservation for a high proportion of patients without compromising survival. Up-front CRT followed by consolidation chemotherapy resulted in a numerically higher WW rate compared to induction chemotherapy followed by CRT. Clinical trial information: NCT02008656 . [Table: see text]

scholarly journals Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3611
Author(s):  
Federica Papaccio ◽  
Susana Roselló ◽  
Marisol Huerta ◽  
Valentina Gambardella ◽  
Noelia Tarazona ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Clinical Staging ◽  
Free Survival ◽  
Short Course ◽  
Disease Free

Most clinical practice guidelines recommend a selective approach for rectal cancer after clinical staging. In low-risk patients, upfront surgery may be an appropriate option. However, in patients with MRI-defined high-risk features such as extramural vascular invasion, multiple nodal involvement or T4 and/or tumors close to or invading the mesorectal fascia, a more intensive preoperative approach is recommended, which may include neoadjuvant or preoperative chemotherapy. The potential benefits include better compliance than postoperative chemotherapy, a higher pathological complete remission rate, which facilitates a non-surgical approach, and earlier treatment of micrometastatic disease with improved disease-free survival compared to standard preoperative chemoradiation or short-course radiation. Two recently reported phase III randomized trials, RAPIDO and PRODIGE 23, show that adding neoadjuvant chemotherapy to either standard short-course radiation or standard long-course chemoradiation in locally advanced rectal cancer patients reduces the risk of metastasis and significantly prolongs disease-related treatment failure and disease-free survival. This review discusses these potentially practice-changing trials and how they may affect our current understanding of treating locally advanced rectal cancers.

Sign in / Sign up

Export Citation Format

Share Document