Oxaliplatin and capecitabine initially concomitant to radiotherapy then administered in the resting period in high-risk locally advanced rectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 581-581
Author(s):  
Pei-Rong Ding ◽  
Yuan-Hong Gao ◽  
Xin An ◽  
Gong Chen ◽  
Feng-Hua Wang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
High Risk ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Radiation Dermatitis ◽  
Consolidation Chemotherapy ◽  
Grade 3 ◽  
The Impact ◽  
Resting Period

581 Background: Although neoadjuvant chemoradiotherapy (CRT) has dramatically reduced the risk of local recurrence in locally advanced rectal cancer (LARC), it fails to reduce the risk of systemic failure. To enhance systemic control, we develop an alternative approach, combining intense chemotherapy using Oxaliplatin and Capecitabine (XELOX regimen) concomitant to radiation and extending the chemotherapy regimen to the resting period (consolidation chemotherapy) for high risk LARC. The aim of the present study was to evaluate the efficacy and toxicities of this strategy. Methods: Patients with high risk LARC were treated with CRT. Two cycles of XELOX regimen was administered concomitant to radiation. Then an additional cycle of the same regimen was extended to the resting period one week after completion of chemoradiation. Tumor response, toxicities associated with CRT and consolidation chemotherapy, and surgical complications were recorded. Results: Thirty-six patients with high risk LARC were identified treated with the strategy from 2010 to 2012. All patents completed the planned dose of radiation and concurrent chemotherapy, and two patient was unable to complete the consolidation chemotherapy because of grade 3 toxicities. Grade 3 acute toxicities were 2.8% leucopenia, 2.8% diarrhea, and 2.8% radiation dermatitis. All patients underwent optimal surgery with TME, among whom sphincter-saving procedure was performed in 27 patients (75%). There was no peri-operative mortality in this cohort. Seven patients (19.4%) developed postoperative complications. Complete regression (pCR), major regression (nearly pCR), and moderate or minimal regression were achieved in 13 (36.1%), 16 patients (44.4%), and 7 patients (19.5%), respectively. Conclusions: The preliminary results suggest that XELOX regimen concomitant to radiation and extended to the “resting period” after radiation completion are well tolerated. This strategy is associated with high pCR and nearly pCR rates. The promising results warrant further investigation of the impact of consolidation chemotherapy following CRT for LARC in future clinical trials.

A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3571-3571 ◽  
Author(s):  
Mercedes Martinez Villacampa ◽  
Jaume Capdevila ◽  
Jose Luis Manzano ◽  
Carles Pericay ◽  
Ramon Salazar ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Correct Selection ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
The Impact

3571 Background: The addition of bevacizumab (BEV) to capecitabine (CAP)-based chemoradiation (CRT) has shown encouraging efficacy in locally advanced rectal cancer (LARC), in nonrandomized studies. This randomized phase II study investigated the effect of adding BEV to preoperative CAP-based CRT in patients (pts), with LARC. Methods: The primary end point was pathologic complete response (pCR). A two-stage design was used. Assuming a minimum pCR rate of at least 15% in one of the arms, a difference between the two arms of 10%, and accepting a probability of correct selection of 87%, 41 pts per arm were needed. Patients with LARC (Stages II-III assessed by MRI) and ECOG PS <2 were randomized to concurrent radiotherapy 45Gy/25f/5 weeks + CAP (825mg/m²/bid) + BEV every 2 weeks (5 mg/kg for 3 doses) (arm A) or the same schedule without BEV (arm B). Surgery was scheduled 6-8 weeks after completing CRT. Results: 90 pts were randomized (arm A/B: 44/46). Patient’s characteristics were well balanced between both arms: male 61%, median age 62 years, median distance from anal verge 7 cm, T3 79%, N+ 87%. 40 (91%)/43 (93%) of pts (arm A/B) finalized the planned CRT + surgery treatment. Overall grade 3-4 toxicity rates were 18 % and 13% (arm A/B, p=0.50); no grade 3-4 hematological toxicity was reported. Postoperative complications were 19(43%)/17(37%)(arm A/B). Efficacy data on patients who actually underwent surgery are reported in the table. Conclusions: The addition of BEV to CAP-based preoperative CRT has shown to be feasible and safe in the local control of LARC. No differences in pCR were observed and longer follow-up is needed to assess the impact on survival endpoints. [Table: see text]

Induction chemotherapy followed by chemoradiotherapy and TME for high-risk locally advanced rectal cancer with and without synchronous resectable metastases.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 599-599 ◽  
Author(s):  
Carla Hajj ◽  
Martin R. Weiser ◽  
Aoife McErlean ◽  
Marc Gollub ◽  
Andrea Cercek ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
High Risk ◽  
Induction Chemotherapy ◽  
Locally Advanced ◽  
Stage Iv ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Stage Iii ◽  
Primary Tumors ◽  
Grade 3

599 Background: Induction chemotherapy (ICT) followed by chemoradiation (CRT) may improve tumor downsizing and disease control among patients (pts) with locally advanced rectal cancer (LARC). We retrospectively assessed the safety and short-term efficacy of ICT followed by CRT and total mesorectal excision (TME) in pts with high-risk LARC with or without synchronous resectable metastases. Methods: We reviewed records of 44 consecutive stage III (n=23) or stage IV synchronous (n=27) pts with LARC treated with ICT followed by CRT between 12/06 – 12/10. Pts had high-risk primary tumors based on advanced T and/or N stage by endorectal ultrasound and/or MRI: T3 (n= 35), T4 (n=7) and N1 (N=18), N2 (n=19). Recurrence-free (RFS) and overall survival (OS) were estimated by Kaplan-Meier methods. Results: Median age was 52 yrs, 66% were female. Pts received a median of 6 cycles of 5-FU based ICT combined with oxaliplatin (n=44). CRT (median dose 50.4 Gy) was delivered with continuous infusion 5-FU; two pts did not complete the prescribed CRT. During induction CT, 10 (22.7%) pts experienced grade 3+ neutropenia. Grade 3+ neutropenia or GI toxicity occurred in 3 (6.8%) and 3 (6.8%) pts, respectively during CRT. Imaging or endoscopic assessment showed that 35 pts had disease regression after ICT, whereas 1 pt progressed and 2 had stable disease. Response to ICT was not assessed in 6 pts. 7 pts did not undergo surgery due to: progression of disease (n=2); comorbid disease (n=2); or pt refusal (n=3). 37 pts proceeded to TME including 17 with known distant metastasis, 16 of whom underwent metastasectomy. 17 pts had tumor response > 90% including 8 with pathologic CR. With a median follow-up of 29.4 mos, 1 pt who underwent TME developed local recurrence. Amongst the 9 pts who had distant recurrences, 7 had initial stage IV disease. The 3-yr RFS among the resected stage III pts was 95%; the 3-yr OS for stage III pts and stage IV pts were 100% and 80% respectively. Conclusions: In this retrospective series, ICT prior to CRT was associated with acceptable toxicity and a substantial incidence of tumor regression. OS and RFS appear promising in this high-risk group of patients.

scholarly journals Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2071
Author(s):  
Jihane Boustani ◽  
Valentin Derangère ◽  
Aurélie Bertaut ◽  
Olivier Adotevi ◽  
Véronique Morgand ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumor Regression Grade ◽  
The Impact

In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0–17) and 0.5 (range, 0–27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.

Primary Tumor Response to Preoperative Chemoradiation With or Without Oxaliplatin in Locally Advanced Rectal Cancer: Pathologic Results of the STAR-01 Randomized Phase III Trial

2011 ◽  
Vol 29 (20) ◽  
pp. 2773-2780 ◽  
Author(s):  
Carlo Aschele ◽  
Luca Cionini ◽  
Sara Lonardi ◽  
Carmine Pinto ◽  
Stefano Cordio ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Primary Tumor ◽  
Tumor Response ◽  
Locally Advanced ◽  
Muscularis Propria ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Iii ◽  
Preoperative Treatment ◽  
The Impact

Purpose To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Patients and Methods Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m2/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m2 weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. Results Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P < .001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P < .001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014). Conclusion Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.

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