scholarly journals Total neoadjuvant treatment of locally advanced rectal cancer with high risk factors in Slovenia

2019 ◽  
Vol 53 (4) ◽  
pp. 465-472
Author(s):  
Mojca Tuta ◽  
Nina Boc ◽  
Erik Brecelj ◽  
Mirko Omejc ◽  
Franc Anderluh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Rectal Cancer ◽  
High Risk ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Distant Recurrence ◽  
High Risk Factors ◽  
Grade 3

Abstract Background In the light of a high rate of distant recurrence and poor compliance of adjuvant chemotherapy in high risk rectal cancer patients the total neoadjuvant treatment was logical approach to gaining acceptance. We aimed to evaluate toxicity and efficiency of this treatment in patients with rectal cancer and high risk factors for local or distant recurrence. Patients and methods Patients with rectal cancer stage II and III and with at least one high risk factor: T4, presence of extramural vein invasion (EMVI), positive extramesorectal lymph nodes or mesorectal fascia (MRF) involvement were treated with four cycles of induction CAPOX/FOLFOX, followed by capecitabine-based radiochemotherapy (CRT) and two consolidation cycles of CAPOX/FOLFOX before the operation. Surgery was scheduled 8–10 weeks after completition of CRT. Results From November 2016 to July 2018 66 patients were evaluable. All patients had stage III disease, 24 (36.4%) had T4 tumors, in 46 (69.7%) EMVI was present and in 47 (71.2%) MRF was involved. After induction chemotherapy, which was completed by 61 (92.4%) of patients, radiologic downstaging of T, N, stage, absence of EMVI or MRF involvement was observed in 42.4%, 62.1%, 36.4%, 69.7% and 68.2%, respectively. All patients completed radiation and 54 (81.8%) patients received both cycles of consolidation chemotherapy. Grade 3 adverse events of neoadjuvant treatment was observed in 4 (6%) patients. Five patients rejected surgery, 3 of them with radiologic complete clinical remissions. One patient did not have definitive surgery of primary tumor due to unexpected cardiac arrest few days after sigmoid colostomy formation. Among 60 operated patients pathological complete response rate was 23.3%, the rate of near complete response was 20% and in 96.7% radical resection was achieved. Pathological T, N and stage downstaging was 65%, 96.7% and 83.4%, respectively. Grade ≥ 3 perioperative complications were anastomotic leakage in 3, pelvic abscess in 1 and paralytic ileus in 2 patients. The rate of pathologic complete response (pCR) in patients irradiated with 3D conformal technique was 12.1% while with IMRT and VMAT it was 37% (p < 0.05). Hypofractionation with larger dose per fraction and simultaneous integrated boost used in the latest two was the only factor associated with pCR. ConclusionsTotal neoadjuvant treatment of high risk rectal cancer is well tolerated and highly effective with excellent tumor and node regression rate and with low toxicity rate. Longer follow up will show if this strategy will improve distant disease control and survival.

A phase II trial of total neoadjuvant treatment (TNT) (Capox plus radiotherapy) for local advanced rectal cancer patients with high risk factors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15025-e15025
Author(s):  
Xin Wang ◽  
Yongyang Yu ◽  
Xiangbing Deng ◽  
Wenjian Meng ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Rectal Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Neoadjuvant Treatment ◽  
Advanced Rectal Cancer ◽  
R0 Resection ◽  
High Risk Factors ◽  
Common Grade ◽  
Grade 3

e15025 Background: Standard neoadjuvant concurrent chemoradiotherapy didn't achieve improved overall survival in stage II-III rectal cancer. Total neoadjuvant treatment (TNT) might be a proper treatment option for patients with high risk factors. Therefore, this phase II trial was conducted to evaluate the safety and efficacy of TNT (Capox and IMRT/VMAT) in rectal cancer patients with high risk factors. Methods:Patients who were diagnosed stage II-III rectal cancer with at least one of the following high risk factors were recruited: cT4b, cN2, EMVI +, MRF+, lateral LN +. Three cycles of induction Capox were followed by pelvic IMRT/VMAT and two cycles of concurrent Capox. Three cycles of consolidation Capox were delivered after radiotherapy. Primary endpoints were pathological complete response (pCR) and R0 resection rate. Secondary endpoints were DFS, OS, toxicities and QOL. Here we present the initial results of this study. Results: From Jun 2015 to Jan 2017, 42 patients were evaluable. One patient (2.4%) who had acute intestinal obstruction after the first cycle of chemotheraoy underwent emergency TME. A total of 27 patients (64.3%) completed 8 cycles of chemotherapy. Forty-one patients (97.6%) completed the planned radiotherapy. 15 of 42 patients (35.7%) achieved a pCR or cCR, in which 12 patients (80%) completed 8 cycles of chemotherapy. Five patients refused the operation and selected Watch & Wait. R0 resection rate of patients who underwent TME were 100%. The mean time of operation was 207 minutes (120-370 minutes). And the mean estimated blood loss was 89ml (10-500ml). The most common grade 3 or higher adverse events associated with the neoadjuvant administration were leucopenia (9.5%), diarrhea (4.8%), radiation dermatitis (4.8%) and thrombocytopenia (2.4%). The most common grade 3 or worse surgery-related complications were pelvic abscesses, anastomotic leaks and hemorrhage which were observed in one patient, respectively. Conclusions: Total neoadjuvant treatment (TNT) is effective and safe for local advanced rectal cancer patients with high risk factors. Long-term efficacies of TNT need to be evaluated.

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 Neoadjuvant Capecitabine and Oxaliplatin Before Concurrent Capecitabine and Radiation in Locally Advanced Rectal Cancers: Experience of a Cancer Hospital in Pakistan

2021 ◽  
pp. 790-796
Author(s):  
Muhammad Atif Mansha ◽  
Asmara Waheed ◽  
Tabinda Sadaf ◽  
Asma Rashid ◽  
Nabia Irfan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Circumferential Resection Margin ◽  
Randomized Clinical Trials ◽  
Resection Margin ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Response Rates ◽  
Complete Response ◽  
Grade 3

PURPOSE To report the toxicity and pathologic response rates after adding neoadjuvant capecitabine and oxaliplatin (CAPOX) followed by concurrent radiation and capecitabine (CAPRT) and surgery in patients with locally advanced rectal cancer. MATERIALS AND METHODS We retrospectively analyzed medical records of 301 patients between January 2007 and December 2014. Patients were treated with four cycles of neoadjuvant chemotherapy comprising CAPOX, followed by radiotherapy at doses of 45-54 Gy in 25-30 fractions with concurrent capecitabine. A response assessment scan was performed at 4-6 weeks postradiation followed by surgical evaluation at 6-8 weeks. Pathologic tumor and nodal response rates as well as circumferential resection margin were assessed on surgical specimens. RESULTS The median age of the patients was 43 years (range, 16-78). Overall, 227 (75.4%) patients were able to complete four cycles of CAPOX. Neoadjuvant chemotherapy was well-tolerated with no serious adverse effects. The most common toxicity was diarrhea (grade 2, n = 108; 35.8%; grade 3, n = 57; 18.9%; grade 4, n = 25; 8.3%) followed by neuropathy (grade 2, n = 132; 43.8%; grade 3, n = 54; 17.9%) and oral mucositis (grade 2, n = 108; 35.8%; grade 3, n = 47; 15.6%; grade 4, n = 9; 2.99%). A total of 229 (76.1%) patients underwent surgery. Pathologic complete response was seen in 52 (22.7%; 95% CI, 13 to 28), whereas 200 (87.3%; 95% CI, 82 to 99) patients had a negative circumferential resection margin on pathology. CONCLUSION Neoadjuvant chemotherapy with CAPOX before CAPRT and planned total mesorectal excision surgery result in good tumor regression and substantial pathologic complete response rates with acceptable toxicity. With growing interest in organ preservation in rectal cancer, the strategy of completing all chemotherapy and chemoradiotherapy before planned surgery offers a favorable paradigm. However, further randomized clinical trials are needed to support this evidence.

Circulating Biomarkers for Response Prediction of Rectal Cancer to Neoadjuvant Chemoradiotherapy

2020 ◽  
Vol 27 (25) ◽  
pp. 4274-4294 ◽  
Author(s):  
Chiara Bedin ◽  
Sara Crotti ◽  
Edoardo D’Angelo ◽  
Sara D’Aronco ◽  
Salvatore Pucciarelli ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Benefit ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Treatment Protocol ◽  
Predictive Biomarkers ◽  
Complete Response ◽  
Tumour Regression

: Rectal cancer response to neoadjuvant Chemoradiotherapy (pCRT) is highly variable. In fact, it has been estimated that only about 21 % of patients show pathologic Complete Response (pCR) after therapy, while in most of the patients a partial or incomplete tumour regression is observed. Consequently, patients with a priori chemoradioresistant tumour should not receive the treatment, which is associated with substantial adverse effects and does not guarantee any clinical benefit. For Locally Advanced Rectal Cancer Patients (LARC), a standardized neoadjuvant treatment protocol is applied, the identification and the usefulness of prognostic or predictive biomarkers can improve the antitumoural treatment strategy, modifying the sequence, dose, and combination of radiotherapy, chemotherapy and surgical resection. : For these reasons, a growing number of studies are actually focussed on the discovery and investigation of new predictive biomarkers of response to pCRT. In this review, we have selected the most recent literature (2012-2017) regarding the employment of blood-based biomarkers potentially predicting pCR in LARC patients and we have critically discussed them to highlight their real clinical benefit and the current limitations of the proposed methodological approaches.

Capecitabine and oxaliplatin as induction and concomitant with radiotherapy in rectal cancer: A phase II study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 604-604
Author(s):  
J. A. Gutierrez ◽  
G. Martinez-Martinez ◽  
A. J. Silva ◽  
J. Gomez Rangel ◽  
M. Palmerin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Induction Treatment ◽  
Ecog Performance Status ◽  
Dermatologic Toxicity ◽  
Grade 3 ◽  
Experienced Grade

604 Background: Preoperative combined modality chemoradiation with fluoropyrimidine-based schedules is widely accepted as the current standard of care for localized rectal cancer. Current strategies have focused on intensifying the neoadjuvant systemic treatment to improve pCR. Methods: From January 2009 to January 2010, 18 patients with locally advanced rectal cancer (T3, any N, M0) were included according to Simon's design. Treatment was 2 cycles of capecitabine 1000 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1) every 3 weeks as induction followed by chemoradiation (45 Gy). During radiotherapy patients received 2 cycles of capecitabine 750 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1 and 8) every 3 weeks. Surgery was planned 5-10 weeks after completion of radiotherapy. The primary endpoint was pCR. Results: 18 patients were assessable for response. Median age was 55 y (41-65), 11 patients with ECOG performance status of 1 (61%), all 18 patients were staged as T3, 10 were staged N+ (56%). Of the 18 patients, 17 patients were given CRT and 13 patients (76%) underwent radical resection. Of the patients who did not underwent resection, 1 patient was considered unresectable at the time of surgery, 2 patients refused surgery because of clinical complete response and 1 patient experienced progressive disease to the spine after chemoradiation. During induction treatment 1 patient (6%) experienced grade 3-4 toxicity (diarrhea). During chemoradiation 1 patient (6%) experienced grade 3 diarrhea and nausea and 1 patient (6%) experienced grade 3 radio-induced dermatologic toxicity; overall grade 3-4 toxicity of 12%. No grade 4 toxicity or treatment related deaths were observed. Of the 13 patients who underwent resection, 12 patients (92%) had a complete resection (R0). Pathologic complete response rate was observed in 1 patient (6%) according to intent to treat. The study was closed after the first stage because it did not reach the minimum required number of pCR. Conclusions: Induction chemotherapy with capecitabine and oxaliplatin before chemoradiation is feasible. Given that we did not reach the prespecified pCR rate required to continue the trial, the study was closed after the first stage. No significant financial relationships to disclose.

The safety and tolerability of veliparib (V) plus capecitabine (C) and radiation (RT) in subjects with locally advanced rectal cancer (LARC): Results of a phase 1b study.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 579-579 ◽  
Author(s):  
Brian G. Czito ◽  
Mary Frances Mulcahy ◽  
Dustin A. Deming ◽  
Houman Vaghefi ◽  
Gayle S. Jameson ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Parp Inhibitor ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Post Surgery ◽  
Tumor Downstaging ◽  
Grade 3 ◽  
Dose Proportional

579 Background: Patients (pts) with LARC treated with neoadjuvant C/RT and then surgery have low rates of pathologic complete response (ypCR) and significant relapse rates. V is a potent, orally bioavailable PARP inhibitor that has been shown to enhance the efficacy of chemotherapy and RT in preclinical models. This study sought to establish the recommended phase 2 dose (RPTD), as well as to assess safety, pharmacokinetics (PK), and preliminary activity of V + RT/C in pts with LARC. Methods: Pts with stage II-III rectal cancer received RT (50.4Gy/1.8Gy/fraction) with C (825 mg/m2 BID) five days per week (W) for 5.5W. Dosing of V (BID, 20mg-400mg) continued from W1D2 to 2 days past RT. Pts underwent surgery 5-10W following RT. Assessments included identification of RPTD with the Exposure Adjusted Continual Reassessment Method, adverse events (AEs), PK, and pathological response (ypCR and tumor downstaging rates). Results: As of August 5, 2014, 30 pts have been enrolled, 24/6 male/female, median age 58 yrs; 1 pt discontinued due to an AE. The most common treatment-emergent AEs possibly or probably related to V (>15% pts, n >4) were nausea (40%), fatigue (37%), diarrhea (30%), vomiting (20%), and dysgeusia (17%). One grade 3/4 event each of anemia and lymphopenia and 2 grade 3/4 events of diarrhea were deemed at least possibly related to V. Two dose limiting toxicities (DLTs) occurred: 1 at 70 mg BID V (radiation skin injury requiring dose interruption); 1 at 400 mg BID (nausea and vomiting requiring discontinuation). The RPTD is 400 mg BID of V in combination with RT/C. PK results from 16 pts suggest that V PK was approximately dose proportional when administered with RT/C and that V had no effect on the PK of C. To date, 18/25 (72%) pts have been downstaged post-surgery; with 7/25 (28%) achieving ypCR. Conclusions: V at 400 mg in combination with RT/C has an acceptable safety profile. 72% of 25 evaluable patients had tumor downstaging post-surgery, including 28% with ypCR. Dose escalation of V resulted in approximately dose-proportional increases in the V PK with no clear effect on C PK. Clinical trial information: NCT01589419.

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