CAPOX Regimen Research Articles

CapeOX as neoadjuvant chemotherapy for locally advanced rectal cancer: might less be more?

BackgroundLocally advanced rectal cancer (LARC) poses unique challenges in treatment, with current neoadjuvant chemoradiotherapy (NA-CRT) showing limitations. The CapeOX regimen emerges as a potential less aggressive neoadjuvant chemotherapy (NAC) for LARC.MethodsWe conducted a retrospective study involving treatment-naïve patients with LARC from March 2014 to March 2021 who received 2–4 cycles of CapeOX NAC followed by radical surgery. Treatment response was evaluated using tumor regression grade (TRG), MRI-based TRG (MRI-TRG), and Neoadjuvant Rectal (NAR) score.Results94.7% of patients experienced symptom improvement and 96.4% achieved sphincter-preserving surgery. Post-NAC showed significant tumor regression and MRI confirmed a tumor length reduction (P < 0.001). Clinical and pathological staging discrepancies post-NAC suggest broader therapeutic advantages. 5-year overall and disease-free survival rates were 78.4% and 73.4%. NAR scores provided better prognostic accuracy than MRI-TRG.ConclusionCapeOX NAC presents notable benefits for LARC patients and its clinical significance may be underestimated. The NAR score demonstrates superior prognostic value over MRI-TRG.

Safety of first-line systemic therapy in patients with metastatic colorectal cancer: a network meta-analysis of randomized controlled trials

ObjectiveTo evaluate the safety of first-line systemic therapy for metastatic colorectal cancer through network meta-analysis.MethodsThe literature from PubMed, Embase, Web of Science, and Cochrane Library databases was searched from the inception of the databases to August 15, 2023, and strict inclusion and exclusion criteria were applied to screen studies. The Cochrane Bias Risk Assessment Tool (RoB 2.0) was used to evaluate the quality of the included literature. Network meta-analysis was conducted using Stata 15.0 and R4.3.1 software to compare the incidence of adverse events (AEs) among different treatment regimens.ResultsA total of 53 randomized controlled trials, involving 17,351 patients with metastatic colorectal cancer (mCRC), were ultimately included, encompassing 29 different therapeutic approaches. According to SUCRA rankings, the CAPOX regimen is most likely to rank first in terms of safety, while the FOLFOXIRI + panitumumab regimen is most likely to rank last. In terms of specific AEs, the CAPOX regimen, whether used alone or in combination with targeted drugs (bevacizumab and cetuximab), is associated with a reduced risk of neutropenia and febrile neutropenia, as well as an increased risk of thrombocytopenia and diarrhea. The FOLFOX regimen, with or without bevacizumab, is linked to an increased risk of neutropenia and peripheral sensory neuropathy. The FOLFIRI/CAPIRI + bevacizumab regimen is associated with a reduced risk of peripheral sensory neuropathy. S-1 and S-1 + oxaliplatin are well-tolerated in terms of gastrointestinal reactions. The FOLFOXIRI regimen, whether used alone or in combination with targeted drugs, is associated with various AEs.ConclusionIn summary, the CAPOX regimen may be the safest option among the first-line systemic treatment regimens for mCRC patients, while the FOLFOXIRI + panitumumab regimen may be associated with a higher incidence of grade 3 or higher AEs.

Three-year survival data from a phase 2 trial of neoadjuvant short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer.

e15611 Background: For locally advanced rectal cancer (LARC), short-course radiotherapy (SCRT) or long-course chemoradiotherapy combined with chemotherapy have been the established neoadjuvant treatment, but the optimal therapeutic modality is still under exploration. We previously reported the short-term results of neoadjuvant SCRT followed by chemotherapy and camrelizumab (a PD-1 inhibitor), encouragingly noting pathological complete response (pCR) in 48.1% of LARC patients (Lin Z et al. J Immunother Cancer 2021;9:e003554). Here, we report the further 3-year follow-up results. Methods: Adult patients with histologically confirmed T3-4N0M0 or T1-4N+M0 rectal adenocarcinoma were enrolled. Prior to surgery, eligible patients received 5×5 Gy SCRT, and after one week, they were treated with camrelizumab (200 mg, i.v., on day 1) plus CAPOX chemotherapy (oxaliplatin 130 mg/m2, i.v., on day 1 and capecitabine 1000 mg/m2, orally, bid, on days 1-14) in 21-day cycles for 2 cycles. Radical surgery was performed one week after the last neoadjuvant cycle. For this updated analysis, disease-free survival (DFS) and overall survival (OS) at 3 years are reported. Results: Thirty patients were enrolled and received SCRT, and all of these patients were included in this OS analysis. Among them, 27 patients received camrelizumab plus CAPOX chemotherapy, all of whom underwent surgery and were included in this DFS analysis. Of the 27 patients, 21 patients (77.8%) received at least one cycle of postoperative adjuvant chemotherapy with CAPOX regimen. With a median follow-up of 40.8 months (IQR 40.3-44.3), disease recurrence or death occurred in six (22.2%) patients. The median DFS and OS were both not reached, with the 3-year DFS and OS rates of 80.2% (95% CI 58.6-91.3) and 93.3% (95% CI 75.9-98.3), respectively. Subgroup analysis showed that patients with pCR, postoperative pathological node-negative status, PD-L1 combined positive score ≥ 1, and negative circumferential resection margin and negative extramural venous invasion by MRI at baseline had a tendency towards improved 3-year DFS and OS compared to those without these characteristics. No new or long-term safety signals were identified. Conclusions: With 3 years of extended follow-up, a favorable survival benefit was observed with neoadjuvant SCRT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery in LARC patients. A randomized phase 3 trial (NCT04928807) is ongoing to confirm these results. Clinical trial information: NCT04231552 .

Optimal duration of oxaliplatin-based adjuvant chemotherapy in patients with different risk factors for stage II-III colon cancer: a meta-analysis.

The duration of oxaliplatin-based chemotherapy in high-risk stage II, low-risk stage III, and high-risk stage III colon cancer (CC) patients is controversial. To reduce the risk of adverse events (AEs) without compromising efficacy while improving chemotherapy compliance is crucial. The authors searched Cochrane, Embase, Pubmed, and Web of Science databases for articles from inception to August 8, 2023, the main outcomes were disease-free survival, overall survival, chemotherapy completion rates, and AE frequency. Six randomized controlled trials (RCTs) involving 10332 patients were included. Disease-free survival analysis revealed that only the high-risk stage III CC patients experienced better results with the 6-month FOLFOX regimen when compared with the 3-month regimen [Hazard ratio (HR): 1.32, 95% CI: 1.15-1.51, P <0.0001). Overall survival (OS) analysis revealed that extending the use of FOLFOX and CAPEOX regimens did not provide survival benefits for stage III CC patients (HR: 1.16, 95% CI: 0.9-1.49, and HR: 0.89, 95% CI: 0.67-1.18, P =0.40). The completion rate of the 3-month oxaliplatin-based adjuvant chemotherapy regimen was significantly higher than that of the 6-month regimen [Relative risk (RR): 1.16, 95% CI: 1.06-1.27, P =0.002]. Moreover, the 3-month regimen had significantly lower AE rates than the 6-month regimen (RR: 0.62, 95% CI: 0.57-0.68, P <0.00001), with differences mainly concentrated in grade 3/4 neutropenia (RR: 0.70, 95% CI: 0.59-0.85, P =0.0002), peripheral sensory neuropathy at ≥grade 2 (RR: 0.45, 95% CI: 0.38-0.53, P <0.00001), and hand-foot syndrome at ≥grade 2 (RR: 0.36, 95% CI: 0.17-0.77, P =0.009). The 6-month FOLFOX regimen should only be recommended for high-risk stage III CC, while the 3-month regimen can be recommended for other stages. A 3-month CAPEOX regimen can be recommended for stage II-III CC.

Low skeletal muscle radiodensity is a risk factor for adjuvant chemotherapy discontinuation in colorectal cancer.

Previously, we reported SMR (skeletal muscle radiodensity) as a potential prognostic marker for colorectal cancer. However, there have been limited studies on the association between SMR and the continuation of adjuvant chemotherapy in colorectal cancer. In this retrospective study, 143 colorectal cancer patients underwent curative surgery and adjuvant chemotherapy using the CAPOX regimen. Patients' SMRs were measured from preoperative CT images and divided into low (bottom quarter) and high (top three quarters) SMR groups. We compared chemotherapy cycles, capecitabine and oxaliplatin doses, and adverse effects in each group. The low SMR group had significantly fewer patients completing adjuvant chemotherapy compared to the high SMR group (44% vs. 68%, P < 0.01). Capecitabine and oxaliplatin doses were also lower in the low SMR group. Incidences of Grade 2 or Grade 3 adverse effects did not differ between groups, but treatment discontinuation due to adverse effects was significantly higher in the low SMR group. Logistic regression analysis revealed Stage III disease (odds ratio 18.09, 95% CI 1.41-231.55) and low SMR (odds ratio 3.26, 95% CI 1.11-9.56) as factors associated with unsuccessful treatment completion. Additionally, a higher proportion of low SMR patients received fewer than 2 cycles of chemotherapy (50% vs. 12%). The low SMR group showed higher treatment incompletion rates and received lower drug doses during adjuvant chemotherapy. Low SMR independently contributed to treatment non-completion in colorectal cancer patients.

Efficacy and Safety of Preoperative Transcatheter Rectal Arterial Chemoembolisation in Patients with Locally Advanced Rectal Cancer: Results from a Prospective, Phase II PCAR Trial

AimsThe PCAR study aimed to assess the efficacy and safety of preoperative transcatheter rectal arterial chemoembolisation (TRACE) in patients with locally advanced rectal cancer (LARC). Materials and methodsThis was a single-centre, prospective, phase II trial conducted in China. Eligible patients were adults aged 18 years and older with histologically confirmed stage II or III rectal carcinoma and an Eastern Cooperative Oncology Group performance status of 0–1. Patients received TRACE with oxaliplatin, followed by radiotherapy with a cumulative dose of 45 Gy (1.8 Gy/time/day, five times a week for 5 weeks) and received oral S1 capsules twice daily (7 days a week for 4 weeks). Patients underwent total mesorectal excision 4–8 weeks after the completion of chemoradiotherapy, followed by mFOLFOX6 or CAPOX regimens for 4–6 months. The hypothesis of this study was that adding TRACE to preoperative neoadjuvant chemoradiotherapy would improve tumour regression and prognosis. The primary end point was the pathological complete response rate; secondary end points included the major pathological response rate, anal preservation rate, 5-year disease-free survival (DFS), 5-year overall survival and treatment-related adverse events. ResultsIn total, 111 LARC patients received TRACE and subsequent scheduled treatment plans. The pathological complete response and major pathological response rates were 20.72% and 48.65%, respectively. The 5-year DFS and 5-year overall survival were 61.89% (95% confidence interval 51.45–74.45) and 74.80% (95% confidence interval 65.05–86.01), respectively. Grade 3–4 toxicities were reported in 29 patients (26.13%). The postoperative complication rate was 21.62%, without serious surgical complications. Multivariate Cox regression analysis showed that ypN stage (hazard ratio = 4.242, 95% confidence interval 2.101–8.564, P = 0.00017) and perineural invasion (hazard ratio = 2.319, 95% confidence interval 1.058–5.084, P = 0.0487) were independent risk factors associated with DFS, whereas ypN stage (hazard ratio = 3.164, 95% confidence interval 1.347–7.432, P = 0.0101), perineural invasion (hazard ratio = 4.118, 95% confidence interval 1.664–10.188, P = 0.0134) and serum carbohydrate antigen 199 (CA199; hazard ratio = 4.142, 95% confidence interval 1.290–13.306, P = 0.0344) were independent predictors for overall survival. ConclusionThe current study provides evidence that adding TRACE to neoadjuvant chemoradiotherapy can improve the pathological remission rate in LARC patients with acceptable toxicity. Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with LARC should be considered.

Neoadjuvant toripalimab plus CapeOX in patients with localized dMMR/MSI-H gastric or esophagogastric junction adenocarcinoma (GC/EGJC): Results from the cohort C of phase II NICE trial.

349 Background: Surgery is the cornerstone of curative therapy for localized GC or EGJC and perioperative chemotherapy seems ineffective for those with dMMR/MSI-H tumors. Chemotherapy may booster antitumor immunity. There is a compelling need to investigate the efficacy of perioperative immunochemotherapy for those with dMMR/MSI-H tumors. Methods: NICE trial is a multicenter, multi-cohort phase II trial (NCT04744649) investigating the safety and efficacy of toripalimab combined with CapeOX regimen as perioperative treatment for localized GC or EGJC of PD-L1 CPS≥5 (IHC 22C3) (cohort A), EBV-positive (cohort B), and dMMR/MSI-H (cohort C). Among those cohorts, the cohort A was compared with the control group of perioperative CapeOX regimen in a randomized controlled trial manner, while the cohort B and C were single arm. In present study, we report the findings of Cohort C, and the patients (pts) received toripalimab 240 mg combined with standard dose CapeOX regimen q3 weeks for 4 cycles before and after surgery. The eligible tumor stages were cT3-4aNxM0 or cT2N+M0 diagnosed by chest and abdominal CT combined with staging laparoscopy as well as negative peritoneal cytology. The primary endpoint was major pathologic response (MPR, &lt;10% viable cells) rate. Multiplex fluorescence immunohistochemistry (mIHC) was utilized to explore changes of immune microenvironment. Results: Between March 2021 and April 2023, 15 pts with dMMR/MSI-H localized GC/GEJC were recruited in Cohort C. Tumor stages were cT3N0(n=2), cT3N1-3 (n=2), cT4aN0 (n=1) and cT4aN1-3 (n=10). 14 pts completed all 4 cycles therapy preoperatively and one patient completed 2 cycles therapy because of AEs. None had disease progression, while one achieved a complete clinical response at radiology and endoscopy and refused surgery and the other 14 pts underwent resection. The R0 resection rate was 100% (14/14). The MPR rate was 92.9% (13/14) and the residual tumor percentage was 33.8% in the other one patient (cT4aN2). pCR rate was 78.6% (11/14). Therapy-related grade 3/4 AEs occurred in 5 pts of safety population (n=15). One patient occurred grade 3 immune-related liver toxicity after 2 cycles treatment and recovered after steroids therapy. No pts died during the perioperative treatment, and one patient died of COVID-19 238 days after surgery without relapse. No disease relapse was observed in all pts. The mIHC revealed a significant reduction in CD20+ B cells, CD3+ T cells, NK dim cells, and M1 macrophages within tumor area after treatment for patients who reached pCR. Conclusions: Neoadjuvant toripalimab and CapeOX regimen for the localized dMMR/MSI-H GC/GEJC is safety with high MPR rate. These data indicate that neoadjuvant immunochemotherapy may potentially become one of the treatment options for these patients. Clinical trial information: NCT04744649 .

Case Report: Primary small bowel adenocarcinoma with peritoneal metastasis responded well to a CapeOX + bevacizumab regimen

BackgroundSmall bowel adenocarcinoma (SBA) is a rare condition often presenting with various non-specific gastrointestinal symptoms, making its diagnosis challenging. Delayed diagnosis is common, as patients may not receive the correct diagnosis until complications arise, necessitating further investigations. Furthermore, the management of SBA patients poses difficulties due to the scarcity of high-quality evidence.Case presentationIn this report, we present the case of an elderly man with SBA in the ileum who arrived at our emergency room with acute abdominal pain. The diagnosis was not made until the SBA caused a perforation, leading to acute abdominal pain. An emergent exploratory laparotomy revealed a 3 cm × 3 cm perforated tumor in the ileum, along with widespread metastatic nodules on the omentum, ascending colon, descending colon, and rectum. Postoperative pathological evaluation confirmed the diagnosis of SBA with peritoneal metastasis (pT4N2M1, stage IV). Following surgery, the patient received palliative systemic chemotherapy, which included the CapeOX regimen and the anti-VEGF monoclonal antibody bevacizumab. Remarkably, the patient responded well to this therapy, displaying good tolerance, and we observed no signs of disease progression. As of now, the patient is in good health and continuing with regular follow-up.ConclusionThe early diagnosis of small bowel adenocarcinoma remains a challenge. Delayed diagnosis can lead to a poor prognosis, underscoring the importance of considering SBA as a potential diagnosis for patients with unexplained abdominal pain and gastrointestinal symptoms. This case also highlights the efficacy of palliative chemotherapy with the CapeOX regimen combined with bevacizumab in controlling SBA.

PACE: A phase III trial of CAPOX versus anti-PD-1 inhibitor as adjuvant therapy for patients with dMMR/MSI-H stage III colon cancer.

TPS3637 Background: Approximately 12% of stage III colon cancer are deficient mismatch repair (dMMR), leading to high levels of microsatellite instability (MSI-H). In the KEYNOTE-177 study, the anti–PD-1 inhibitor Pembrolizumab alone significantly improved progression free survival (PFS) versus chemotherapy as first-line therapy for metastatic colorectal cancer (mCRC) patients with MSI-H/dMMR. We are conducting a phase III randomised trial to determine whether anti-PD-1 inhibitor Sintilimab monotherapy can improve disease free survival (DFS) compared with standard adjuvant chemotherapy in stage III colon cancer patients with dMMR. Methods: This is an open-label, multicentre, randomised phase III study. Patients aged ≥ 18 years with completely resected, stage III colon cancer confirmed to have dMMR/MSI-H and ECOG performance status 0-1 are eligible. Approximately 323 patients will be randomly assigned 1:1 to either Sintilimab monotherapy (200 mg IV every 3 weeks for 8 cycles) or CAPOX regimen (capecitabine, oxaliplatin for 4 or 8 cycles according to current standard practice). Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. Primary endpoint is 3-year DFS. The study was estimated to provide approximately 80% power to detect a hazard ratio of 0.56 for DFS at a two-sided alpha of 0.05. Secondary endpoints include OS, safety profile, toxicity, and quality of life. Archived tumor tissue and blood samples will be collected for correlative studies. Study enrollment is ongoing. Clinical trial information: NCT05236972 .

Application of short-course radiotherapy with total neoadjuvant therapy in the treatment of middle and low rectal cancer

Objective: To compare the efficacy and safety of short-course radiotherapy with total neoadjuvant therapy (SCRT-TNT) and neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced middle and low rectal cancer. Methods: A retrospective cohort study was carried out. A of 126 patients with locally advanced middle and low rectal cancer who were treated in the Department of Gastrointestinal Cancer Surgery of Fujian Cancer Hospital from September 2016 to March 2020 were enrolled, including 73 males and 53 females, with a mean age of (56.5±9.8) (23-77) years. Based on neoadjuvant regimen (nCRT treatment was performed before December 2018 and SCRT-TNT treatment was carried out after January 2019), patients were divided into nCRT group (n=68) and SCRT-TNT group (n=58). There were no statistically significant differences in age, sex, distance from tumor to anal verge, Eastern Cooperative Oncology Group (ECOG) performance status and clinical TNM stage between the two groups (all P>0.05). Patients in both groups received pelvic intensity-modulated radiotherapy (IMRT). The radiotherapy dose of nCRT group was 50Gy/25 times/5 weeks. Patients in nCRT group received oral capecitabine chemotherapy during radiotherapy and underwent surgery 6-8 weeks after chemoradiation. However, patients in SCRT-TNT group received CapeOX regimen (oxaliplatin+capecitabine) for 2 cycles of induction chemotherapy, followed by short-course radiotherapy (25Gy/5 times/5 days), then underwent a radical surgery two weeks after completion of consolidation chemotherapy (4 cycles). The adverse reactions, perioperative safety and efficacy of neoadjuvant therapy were compared and analyzed between the two groups. Results: Both groups completed neoadjuvant therapy as planned. Patients in nCRT group and SCRT-TNT group had similar incidence of adverse reactions to radiotherapy and chemotherapy, however, there were no statistically significant differences in the incidence of surgical complications, operation time, intraoperative blood loss and postoperative length of hospital stay (all P>0.05). A total of 119 patients underwent total mesenterectomy (TME), including 64 patients in the nCRT group and 55 patients in the SCRT-TNT group, all with R0 resection. The pathological complete response (pCR) rate was 10.9% (7/64) in the nCRT group and 25.5% (14/55) in the SCRT-TNT group, respectively, with a statistically significant difference (P=0.038). Two years after surgery, there was no statistically significant difference in local recurrence rate and overall survival rate between the two groups (both P>0.05). However, the clinical metastasis rate of SCRT-TNT group was significantly lower than that of nCRT group (20.3% vs 9.1%), with a statistically significant difference (P<0. 05). Conclusion: SCRT-TNT do not increase the adverse reactions of radio chemotherapy and perioperative risks in the treatment of locally advanced middle and low rectal cancer, and the tumor regression effect is good, which is worthy of clinical promotion.

Prognostic Significance of the Gustave-Roussy Immune Score in Colon Cancer Patients Treated with Adjuvant CAPEOX Regimen

Prognostic Significance of the Gustave-Roussy Immune Score in Colon Cancer Patients Treated with Adjuvant CAPEOX Regimen

Impact of Induction Chemotherapy Antecedent to Long Course Neoadjuvant Concurrent Chemo-Radiotherapy on Clinical Outcomes of Patients with Carcinoma Rectum: Retrospective Audit from a Tertiary Cancer Center

<h3>Purpose/Objective(s)</h3> The paradigm of management of locally advanced rectal (T3/4; T1-4N1-2) cancers (LARC) have been shifting to induction chemotherapy (NACT) with long course neoadjuvant chemo-radiotherapy (NACRT) followed by total mesorectal excision (TME) inching towards total neoadjuvant therapy approach. We aimed to evaluate the outcomes of NACRT alone (Arm A) versus NACT followed by NACRT (Arm B) in LARC treated at our center. <h3>Materials/Methods</h3> Data of 101 patients of LARC (March 2013 – Jan 2021) were retrieved for this retrospective analysis. NACT in Arm B consisted of 2 cycles of CAPOX [oxaliplatin (130 mg/m² day 1) and capecitabine (1000 mg/m² twice daily for 14 days) repeated every 3 weeks]. Radiotherapy (RT) in both the arms was 50.4 Gray in 28 fractions with capecitabine 825 mg/m² twice daily on days of RT. All patients underwent TME. Adjuvant chemotherapy (ACT) consisted of CAPOX regimen. Pathological complete response (pCR) and overall complete response OCR (pCR plus near complete response) were defined as per modified Ryan grading system. Disease-free survival (DFS) and overall survival (OS) were assessed with Kaplan Meier method. <h3>Results</h3> Patient characteristics are summarized in Table 1. Median number of NACT cycles in Arm B was two (range 2-4). Median radiotherapy dose was 50.4 Gray. pCR rates were 12.7% in arm B and 7.3% (3/41) in arm A (p=0.516). OCR rates were 28.3% (17/60) in Arm B vs 12.1% (5/41) in Arm A (p=0.044). 2-Year DFS and OS in Arm A versus B were 47.5% vs. 73.9% (p=0.781) and 54.3% vs 67.3% (p= 0.371) respectively. Patients with pCR vs no pCR had better 2-year DFS and OS 88.9% vs 50.1% (p = 0.009) and 83.3% vs 55.4% (p = 0.015) respectively. Patients with OCR vs no OCR had better 2-year DFS and OS 88.5% vs 45.2% (p = 0.009) and 94.4% vs 51% (p = 0.015) respectively. Patients with positive circumferential margin (CRM) and regional node at presentation had poorer DFS 18.6% vs 83.6% (p=0.03) and 42.7% vs 54.9% (p=0.004) respectively. <h3>Conclusion</h3> NACT prior to NACTRT leads to higher OCR rates in LARC. pCR and OCR predicted better DFS and OS and positive CRM and node positivity at presentation portended poorer outcome in our cohort of patients.

＜Editors' Choice＞ Clinical impact of standardized creatinine on dose adjustment of capecitabine.

ABSTRACTAlthough the Cockcroft-Gault equation is still used for the dose adjustment of many drugs that have been approved prior to creatinine standardization, the clinical impact of standardized creatinine in the dose adjustment of capecitabine is poorly understood. We focused on patients with borderline renal function and evaluated the tolerability and safety of capecitabine in patients who received capecitabine plus oxaliplatin (Cape-Ox). We retrospectively identified patients with resected colorectal cancer who had received adjuvant therapy with Cape-Ox regimen. Creatinine clearance (CrCL) was calculated by the Cockcroft–Gault equation with standardized creatinine measured using enzymatic methods, and adjusted CrCL was estimated by adding 0.2 (mg/dL) to the serum creatinine in the equation. We defined patients with “pseudo-normal” renal function as those who had an adjusted CrCL of ≤50 mL/min in patients with normal renal function (CrCL >50 mL/min). We evaluated the tolerability and grade 2 or severer adverse events of capecitabine treatment. One hundred four patients had normal and 10 had impaired renal function (CrCL <50 mL/min). Among the 104 patients with normal renal function, 23 (22.1%) had pseudo-normal renal function. Seventeen patients completed the eight cycles of Cape-Ox therapy without treatment delay or dose reduction, and all of them had truly normal renal function. The patients with pseudo-normal renal function were more likely to have grade 2 or severer thrombocytopenia than those with truly normal renal function. We should recognize correctly the clinical impact of standardized creatinine in the treatment of borderline renal function with Cape-Ox regimen in patients.

Evaluation of chemotherapeutic regimen and associated adverse drug reactions of colorectal cancer in a tertiary care hospital

Background: Colorectal cancer (CRC) is the fourth most common cause of death diagnosed in both men and women. Though there are modifiable and non-modifiable risk factors for CRC. cancer patients encounter chemotherapy-associated drug interactions and adverse drug reactions hence the need for such a study will help the professionals to improve the patient’s quality of life. Materials and Methods: A six-month retrospective study of 130 patients who satisfied the inclusion and exclusion criteria was conducted by collecting data from November 2020 to May 2021. Data was collected from the Mediware system of the hospital using specially designed data collection forms. Results: Out of 130 patients, 61.51% were male and most of the patients were more than 60 years old. In this study, 11 patients had a history of smoking and alcoholism and 4% had a family history of CRC. Comorbidities associated with CRC were HTN and DM. In the study, stage 4 cancer patients were found to be more. 77.69% of patients had received chemotherapy along with surgery, and the most commonly prescribed regimen was Capcetabine and OxaliplatinThe length of hospital stay was increased for the FOLFOX (Oxaliplatin, 5-Fluorouracil, and Leucovorin) regimen. The common ADR analyzed was constipation, followed by vomiting and neutropenia, and most ADRs were associated with the CAPOX regimen (diarrhea) and treated accordingly.10 patients had febrile neutropenia, 5 patients had grade 4 neutropenia and all were treated with antibiotics and filgrastim. Febrile neutropenia was seen in patients with metastasis. Conclusion: Timely and appropriate treatment for ADRs and early screening can improve the quality of life of individuals. Further studies on this topic will help to improve the treatment quality provided by professionals

Intentional Watch and Wait or Organ Preservation Surgery Following Neoadjuvant Chemoradiotherapy Plus Consolidation CAPEOX for MRI-defined Low-risk Rectal Cancer: Findings From a Prospective Phase 2 Trial (PKUCH-R01 Trial, NCT02860234).

To assess the efficacy and safety of intentional watch and wait (W&W) and organ preservation surgery following neoadjuvant chemoradiotherapy plus consolidation CAPEOX in magnetic resonance imaging (MRI)-defined low-risk rectal cancer. Clinical T2/early T3 rectal cancers can achieve high yield pathological complete response (ypCR) rates after chemoradiotherapy; thus, an intentional W&W or organ preservation strategy for good clinical responders in these subgroups can be further tested. This prospective, single-arm, phase 2 trial enrolled patients with low-risk MRI prestaged rectal cancers, who concurrently received chemoradiation, followed by four 3-weekly cycles of CAPEOX regimen. Following reassessment, clinical complete response (cCR) or near-cCR patients underwent W&W/organ preservation surgery; the primary endpoint was a 3-year organ preservation rate. Of the 64 participants, 58 completed treatment, with 6.4% and 33.9% grade 3 to 4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively, during a median 39.5-month follow-up. Initial cCR, and non-cCR occurred in 33, 13, and 18 patients, respectively. Of the 31 cCR and 7 near-cCR cases managed by W&W, local regrowth occurred in 7; of these, 6 received salvage surgery. The estimated 2-year local regrowth rates were 12.9% [95% confidence interval (CI): 1.1%-24.7%] in cCR and 42.9% (95% CI: 6.2%-79.6%) in near-cCR cases, respectively. Eight patients received local excision, including 2 with regrowth salvage. Lung metastases occurred in 3 patients and multiple metastasis occurred in 1 patient; no local recurrence occurred. The estimated 3-year organ preservation rate was 67.2% (95% CI: 55.6%-78.8%). The estimated 3-year cancer-specific survival, non-regrowth disease-free survival, and stoma-free survival were 96.6% (95% CI: 92.1%-100%), 92.2% (95% CI: 85.5%-98.9%), and 82.7% (95% CI: 73.5%-91.9%), respectively. Chemoradiotherapy plus consolidation CAPEOX for MRI-defined low-risk rectal cancer can lead to high rates of organ preservation through intentional W&W or local excision. The oncologic safety of this strategy should be further tested.

A randomized, controlled, multi-center, open-label study of adjuvant nab-paclitaxel plus S-1 (AS) versus capecitabine plus oxaliplatin (CapeOX) for stage III gastric cancer after D2 resection.

4052 Background: There was no prospective randomized study compared taxanes plus fluoropyrimidine versus platinum plus fluoropyrimidine in adjuvant chemotherapy for advanced gastric cancer. Nab-paclitaxel is nanoparticle albumin-bound formulation, showed a potentially efficacy in gastric cancer. We designed this trial to compare the effective and safety of AS and CapeOX regimen for gastric adenocarcinoma adjuvant therapy. Methods: Patients with stage III gastric or gastroesophageal junction adenocarcinoma who had D2 surgery and achieved R0 resection were randomized 1:1 to AS group and CapeOX. Randomization was stratified by differentiation type (differentiated vs. undifferentiated) and AJCC/UICC pathological stage (IIIA vs. IIIB, IIIC). AS group: Nab-paclitaxel 100 mg/m2 on d1 and d8; S-1 80-120mg/d, p.o., bid on d1-d14; repeated every 21 days for 8 cycles. CapeOX group: oxaliplatin 130 mg/m2 on d1; capecitabine 1000 mg/m2, p.o., bid on d1-d14; repeated every 21 days for 8 cycles. The primary endpoint is 3-year disease-free survival (3-year-DFS) rate, the secondary endpoints included overall survival (OS), and safety. Results: Between March, 2020 to Jan, 2022, 146 subjects were enrolled to receive either AS regimen (n = 71) or CapeOX regimen (n = 75). The baseline characteristics between two arms were generally balanced. The 1-year DFS rate was 95.50% and 72.84% in AS and CapeOX group, respectively. At the cutoff date, 3 patients (the recurrence sites were peritoneum [n = 1], locoregional [n = 1] and distant [n = 1]) in AS group had relapsed, compared with 10 patients (peritoneum [n = 2], locoregional [n = 4] and distant [n = 4]) in CapeOX group. 4 subjects in CapeOX group died compared with 0 in AS group. A total of 42 patients (AS, n = 21 [29.58%]; CapeOX, n = 21 [28.00%]) needed dose reduction main due to hematological toxicity. The median relative dose intensity of Nab-paclitaxel, S-1, oxaliplatin and capecitabine was 82.55%, 91.30%%, 83.16%% and 78.95%, respectively. Treatments were delayed in 82 of 297 (27.61%, 24 due to hematological and 15 due to non-hematological toxicity) cycles at AS group and in 100 of 319 (31.35%, 18 due to hematological and 13 due to non-hematological toxicity) cycles at CapeOX group. There were 34 (47.89%) patients in AS group and 30 (40.00%) patients in CapeOX group occurred treatment-related adverse events (TRAEs), though most of them were grade I-II. Main grade III-IV AEs were neutropenia (28.16% in AS group vs 8.00% in CapeOX group), leucopenia (15.49% vs 1.33%), thrombocytopenia (0% vs 8.00%) and anemia (5.63% vs 1.33%). Conclusions: Adjuvant AS regimen showed a trend towards better DFS compared with CapeOX regimen, and is a potentially regimen for stage III gastric cancer after curative D2 gastrectomy, with tolerable toxicity. Long-term survival benefit requires more data. Clinical trial information: NCT04135781.

Study of the effectiveness of chemotherapy in patients with colorectal cancer depending on the location of the metastatic lesion.

e15540 Background: The reason for the increased interest in the chemotherapeutic treatment of metastatic colorectal cancer (CRC) is the steady increase in the incidence of this oncological pathology, as well as the high incidence of neglect of the tumor process in a significant proportion of patients in the absence of improvement in long-term treatment results. Methods: In 84 patients with metastatic CRC (mCRC), the clinical effect and toxicity of the FOLFOX4 and CAPOX regimens were studied. In 51 (60.7%) patients, multiple metastases in various organs were most common, in 18 (21.4%) - solitary, and only in 15 (17.9%) patients - solitary. Among the examined patients, men accounted for 46 (54.7%), women - 38 (45.2%). The average age of men was 57.2+0.2 years, women 65.4+0.4 years. Patients underwent 2-4 courses of treatment, after which the effect of PCT was evaluated according to the REGIST scale (2009). Results: Out of 84 patients with mCRC who received 2-4 courses of palliative chemotherapy according to the FOLFOX4 and CAPOX regimens, complete regression of the process was observed in 14 (16.7%) patients, partial regression in 34 (40.5%) patients, stabilization of the process in 19 (22.6%) and in 17 (20.2%) progression of the disease was revealed. At the same time, the highest objective response rate (PR + FR) was with metastases in the liver - 16 (76.1%) and lungs - 12 (63.1%). Of the 3 patients with brain metastases, stabilization was noted in 2 cases and progression of the process in 1 case. With combined distant metastases (lungs + liver and lungs + bones), there were 2-3 times more patients who were not sensitive to therapy than those who were sensitive. With combined distant metastases (lungs + liver and lungs + bones), there were 2-3 times more patients who did not respond to therapy than those who were sensitive to treatment. The “treatment sensitive” group included 48 (57.1%) patients with complete and partial regression. The “treatment-resistant” group consisted of 36 (42.9%) patients with progression and stabilization of the disease. Conclusions: The highest objective response rate (PR+FR) in patients with mCRC was with metastases in the liver - 16 (76.1%) and lungs - 12 (63.1%). The comparatively better results in metastatic lesions of the liver and lungs are obviously associated with a more developed blood supply to these organs, which leads to a better supply of chemotherapy drugs and the effectiveness of treatment. At the same time, the combination of localization of CRC metastatic lesions in various organs significantly worsens the results of treatment.

The clinical efficacy and safety of neoadjuvant chemoradiation therapy with immunotherapy for the organ preservation of ultra low rectal cancer: A single arm and open label exploratory study.

e15603 Background: Neoadjuvant chemoradiotherapy (nCRT) not only could bring tumor downsizing and downstaging but also could achieve clinical complete response (cCR) or pathological complete response (pCR). Although immunotherapy benefits MSI-H/dMMR rectal cancer patients, little response is observed in MSS/pMMR patients. Several clinical trials including VOLTAGE trial demonstrated that a combination of PD-1 inhibitor and nCRT could result in a promising pathological response even in MSS/pMMR patients. But the elucidation regarding organ preservation after treatment is lacking. Watch and Wait (W&amp;W) is an effective strategy in rectal cancer patients showing cCR after nCRT to preserve organs. This study was designed to explore the efficacy, safety, and organ preservation rate of a combination of nCRT and PD-1 inhibitor(sintilimab) in MSS/pMMR patients with ultra-low rectal cancers. Methods: This was a single-arm, phase II trial. Patients with ultra-low rectal cancer that was confirmed as MSS/pMMR T1-3aN0-1M0 and received 50 Gy (25×2 Gy) chemoradiotherapy and 2 cycles of sintilimab, followed by 6 cycles of capecitabine or CAPOX regimen plus 2 cycles of sintilimab as consolidation therapy. Patients with cCR were managed using the W&amp;W strategy, patients with ncCR were given local excision. The primary outcome was cCR rate and secondary outcomes were anal preservation rate, organ preservation rate, tumor regression grade (TRG), and safety profile. Results: From 2021 January to 2021 December, a total of 23 patients were enrolled. The median age was 55 y (range; 38 to 75). Male patients were 61%. cT2 was 56.5% (13/23), cT3 was 43.5% (10/23), cN0 was 69.6% (16/23), and cN1 was 30.4% (7/23). All patients completed 50Gy chemoradiotherapy. Nineteen patients received 4 cycles of sintilimab treatment, 3 patients received 3 cycles of sintilimab, and 1 patient received 1 cycle of sintilimab. cCR was 43.5% (10/23), ncCR was 26.1% (6/23), and cPR was 30.4% (7/23). The anal preservation rate was not assessed in 1 patient due to cerebral ischemic stroke. The anal preservation rate was 95.5% (21/22), rectal preservation rate was 59.1% (13/22). Ten patients underwent surgery. Among them, two patients achieved pCR, and the major pathologic response rate (TRG0-1) was 60.0% (6/10). The overall CR(cCR+pCR) rate was 52.2% (12/23). Grade 3/4 treatment-related adverse events occurred in 17.4% (4/23) of patients. No unexpected adverse events or deaths were observed. Conclusions: Given the favorable tolerability and encouraging cCR rate, nCRT plus sintilimab could be a feasible and safe option for patients with pMMR/MSS, ultra-low rectal cancer who have a strong desire to preserve the anus. Based on these results, a prospective, randomized, controlled, multicenter, phase III study is currently in progress (NCT05215379). Clinical trial information: ChiCTR2100042785.

P-177 Sex differences in chemotherapy-induced toxicities in gastric cancer patients

Female patients have a higher risk for chemotherapy toxicities due to sex differences related to pharmacokinetics and pharmacodinamics. In the era of evolving gender-medicine, sex-adjusted therapies are earning a role and may become a reality. In this study we aim to detect sex differences for toxicities in gastric cancer patients. This retrospective analysis included all gastric cancer patients treated with curative intent between january 1st 2017 and december 31st 2021, in a Portuguese hospital. All patients included did a minimum of 5 chemotherapy cycles. Patients with dihydropyrimidine dehydrogenase deficiency were excluded. Data regarding treatment and related toxicity was collected and compared between male and female sex. Toxicities were recorded using Common Terminology Criteria for Adverse Events, version 5. A descriptive analysis was performed using SPSS®, the Mann-Whitney and Chi-square test were used for continuous and categorical variables, respectively. A total of 72 patients were included, 61,1% were men and 38,9% women with a median age of 66 vs 62 years, respectively (p=0.441) and an ECOG of 0-1. 22 patients did adjuvant chemotherapy preferably with CAPOX regimen (women: 62,5%, men: 64,3%) and 50 patients underwent perioperative chemotherapy mostly with FLOT regimen (women: 75%, men: 83,3%). For grade ≥ 3 reported toxicities, there were no differences between women and men (71,4% vs 59,1%, p=0,288). Higher rates of nausea and vomiting were reported in female sex, both all grade (82,1% vs 52,3%, p=0,015), and grade ≥ 2 (46,4% vs 15,9%, p=0.005). Women experienced more mucositis episodes, both all grade (32,1% vs 11,4%, p=0.034) and grade ≥ 2 (10,7% vs 0%, p=0.027). Other gastrointestinal toxicities such as diarrhea grade ≥ 2 and all grade anorexia were more likely experienced by women (21,4 vs 18,2% and 64,3% vs 45,4%), although statistical significance was not reached. There were no differences in all grade hematologic toxicities, although women tendentially had higher rates of all grade anemia (82,1% vs 59,1%, p=0,120) and neutropenia (42,8% vs 34%, p=0,657), still men experienced more thrombocytopenia (68,2% vs 42,8%, p=0.161). All grade neuropathy was more prevalent in men, particularly with FLOT regimen (92% vs 73,4%, p=0,105). Of all patients, both sexes underwent a median of 8 cycles. The percentage dose of fluoropyrimidine, oxaliplatin and docetaxel administered was lower in women, with results closer to significance with docetaxel (75,3% vs 88%, p=0,058). Women experienced dose reductions more frequently than men (92,9 vs 72,7%, p=0,035), and also dose delays (75% vs 59,1%, p=0,167). Our results showed that women experience more gastrointestinal toxicities such as nausea/vomiting and mucositis, and tendentially more hematologic toxicities than men. Consequently, dose reductions were significantly more frequent in women, which reinforces the importance of future sex-related interventions in systemic therapy to improve treatment tolerability. Study limitations must be considered such as: its retrospective nature and small sample size, possibly underreported toxicities by clinicians and differences in reporting due to different perceptions of toxicities by both sexes. The consequences of toxicity sex differences must be taken in consideration and its impact in treatment compliance, efficacy and survival further studied.

Prognostic impact of early treatment discontinuation and early oxaliplatin discontinuation in patients treated with 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer: an ACCENT/IDEA pooled analysis of 11 trials.

11 Background: Six months of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) remains a standard in high-risk stage III patients. Early treatment discontinuation (ETD) could worsen the prognosis. In addition, there is current lack of data on the prognostic impact of early oxaliplatin only discontinuation (EOD). Methods: We studied the prognostic impact of ETD and EOD in patients with stage III CC who participated in 11 relevant clinical trials of the ACCENT and IDEA databases, where patients were planned to receive 6 months of adjuvant fluoropyrimidine plus oxaliplatin (FOLFOX or CAPOX). ETD was defined as discontinuation of treatment before 75% of cycles of chemotherapy. EOD was defined as discontinuation of oxaliplatin only, while continuing the fluoropyrimidine, before 75% of cycles of oxaliplatin. Association between ETD/EOD and overall survival (OS) and disease-free survival (DFS) was assessed by Cox model adjusted for prognostic factors. Results: ETD analysis included 10,444 patients (FOLFOX n = 7,033; CAPOX n = 3,411), with 20.9% of patients with ETD (17.8% with FOLFOX and 27.2% with CAPOX, p &lt; 0.001). Out of 7,243 patients, 18.8% experienced EOD (17.4% FOLFOX versus 21.4% with CAPOX, p &lt; 0.001). Compared to patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, older, with higher ECOG-PS ≥ 1, and in addition for ETD, a Body Mass Index (BMI) &lt; 18.5 kg/m2. In multivariate analyses, ETD was associated with a decrease in DFS and OS in the overall population (HR: 1.40 95%CI 1.23-1.58, p &lt; 0.001 and HR: 1.51 95%CI 1.31-1.74, p &lt; 0.001, respectively). The same pattern was present with FOLFOX and CAPOX regimen, and also in low-risk and high-risk groups for each regimen with the exception of the CAPOX regimen in the low-risk group for DFS and OS. By contrast, EOD was not associated with reduced DFS or OS in the overall population (HR: 1.10 95%CI 0.77-1.58, p = 0.6 and HR: 0.97 95%CI 0.62-1.52, p = 0.9, respectively), in the low-risk group (HR: 0.97 95%CI 0.56-1.66, p = 0.9 and HR: 0.97 95%CI 0.51-1.82, p = 0.9, respectively) and high-risk group (HR: 1.22 95%CI 0.74-2.02, p = 0.4 and HR: 1.05 95%CI 0.53-2.08, p = 0.9, respectively) and for all subgroups of regimen. Conclusions: In patients treated with 6 months of oxaliplatin-based adjuvant chemotherapy for stage III CC, ETD was associated with a decrease in DFS and OS. By contrast, EOD was not significantly associated with poorer outcomes. In case of relevant neurotoxicity during a 6 months schedule, these data are not in favor of continuing oxaliplatin beyond 75% of planned cycles of adjuvant chemotherapy, and demonstrate that fluoropyrimidines remain the cornerstone of adjuvant chemotherapy in localized CC.