Safety Of Capecitabine Research Articles

Clinical effect analysis of different regimens of capecitabine in the treatment of patients with advanced colon cancer

To assess the efficacy and safety of capecitabine in treating advanced colon cancer. Patients with advanced colon cancer were randomized into three groups: control group (n = 50, daily dose 2,500 mg/m2), the medium-dose group (n = 50, daily dose 2,000 mg/m2), and the low-dose group (n = 50, daily dose 1,500 mg/m2) capecitabine for 4 cycles(12 weeks). Afterwards, the response rate, quality of life, and adverse reactions of the three groups were collected for comparison. Efficacy rates were 50%, 70%, and 72%, respectively, with the low-dose group showing the highest efficacy (χ2 = 6.424, p = 0.040); Quality of life comparison results indicated significant differences in physical function (F = 98.528, p < 0.001), role function (F = 123.418, p < 0.001), social function(F = 89.539, p < 0.001), emotional function (6 F = 77.295, p < 0.001), cognitive function (F = 83.529, p < 0.001), and overall quality of life (F = 99.528, p < 0.001) among the three groups, and the three groups returned consistent scores, with the low-dose group scoring highest. Incidence rates were 86.00%, 46.00%, 34.00%, with the control group having the highest rate (χ2 = 16.505, p < 0.001). Capecitabine at a dosage of 1,500 mg/m2 demonstrated a good therapeutic effect and improved the quality of life in patients with advanced colon cancer, with a lower incidence of adverse reactions. A prolonged treatment cycle with reduced dosage is suggested to further improve treatment outcomes and patient prognosis. Trial registration The study was registered on clicaltrials.gov ‘NCT06246461’ on 30/01/2024.

Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial.

This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

QUATTRO-II randomized trial: CAPOXIRI+bevacizumab vs. FOLFOXIRI+bevacizumab as first-line treatment in patients with mCRC

The QUATTRO-II trial examined the efficacy and safety of capecitabine+oxaliplatin+irinotecan (CAPOXIRI)+bevacizumab (BEV) vs. 5-fluorouracil+folinic acid+oxaliplatin+irinotecan (FOLFOXIRI)+BEV in metastatic colorectal cancer (mCRC). In this phase II study (ClinicalTrials.gov: NCT04097444; jRCTs041190072), patients were randomized (1:1) to FOLFOXIRI+BEV or CAPOXIRI+BEV. The induction treatment in the FOLFOXIRI+BEV/CAPOXIRI+BEV arms was continued for 8/6 cycles (maximum 12/8 cycles if feasible), and the maintenance treatment was 5-fluorouracil/leucovorin+BEV or capecitabine+BEV at the investigators' discretion. The primary endpoint was progression-free survival (PFS), with the two arms deemed equivalent if the hazard ratio (HR) of the point estimate was 0.80<HR<1.25. Secondary endpoints were overall response rate (ORR), overall survival (OS), incidence of adverse events (AEs), and patient-reported outcomes. Overall, 51 and 52 patients were randomized to FOLFOXIRI+BEV and CAPOXIRI+BEV, respectively. The study met itsprimary endpoint; PFS at median follow-up of 23.7 months was 10.6 months (95% confidence interval [CI], 7.7-13.3) in the FOLFOXIRI+BEV arm vs. 10.9months (95% CI, 9.3-14.3) in the CAPOXIRI+BEV arm (HR1.114 [0.80<HR<1.25], p= 0.654). In the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms, the 2-year OS rate (95% CI) was 65.5% (49.5%-77.6%) vs. 74.3% (59.8%-84.2%), and the ORR (95% CI) was 76.5% (62.5%-87.2%) vs. 84.6% (71.9%-93.1%). Major (grade ≥3) AEs in the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms were neutropenia (68.6% vs. 40.4%), febrile neutropenia (9.8% vs. 11.5%), diarrhea (7.8% vs. 17.3%), and appetite loss (7.8% vs. 17.3%). CAPOXIRI+BEV was well tolerated with reduced hematological toxicity and efficacy comparable to those of FOLFOXIRI+BEV, providing a potentially convenient first-line treatment alternative to FOLFOXIRI+BEV in patients with mCRC. Chugai Pharmaceutical Co., Ltd.

Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater

BackgroundAdenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting.MethodsThis investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy.ResultsFrom January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78–5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56–11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49–4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47–5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3–4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%).ConclusionsThis study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

A retrospective analysis of the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) and docetaxel plus S-1 (DS) as adjuvant chemotherapy for pathological stage III (p stage III) gastric cancer (GC).

342 Background: Adjuvant chemotherapy following surgical resection is the standard treatment for patients with p stage III GC in Japan. Although CapeOX and DS are available for adjuvant chemotherapy for stage III GC, there is limited data on which treatment is more effective. We aim to compare the efficacy and safety of CapeOX and DS as adjuvant chemotherapy in patients with p stage III GC. Methods: We extracted data of patients with p stage III GC who received either CapeOX (capecitabine on days 1–14 plus oxaliplatin on day1 for 8 cycles [q 3week]) or DS (S-1 on days 1–14 at 1st cycle [q 3 week], docetaxel on day 1 plus S-1 on days 1–14 during 2–7 cycles [q 3 week], and S-1 on days 1–28 up to 1 year [q 6 week]) as adjuvant chemotherapy after surgical resection at our institution from February 2016 to May 2022. Three-year relapse-free survival (RFS) and adverse events (AEs) were assessed. Cox proportional hazard model was used in multivariable analysis to assess the effect of independent variables on RFS. Results: A total of 74 patients were included in this study (CapeOX 31/ DS 43). Patient characteristics (CapeOX/DS) were as follows: median age, 60/64 years; male, 77/65 %; ECOG-PS 0/1, 45%/44%, 55%/56 %; p stage IIIA/IIIB/IIIC, 10%/30%, 48%/51 %, 42%/19 %. The 3-year RFS was 37% in the (hazard ratio [HR] = 0.81, P=0.48). For p stage IIIA, IIIB, and IIIC, the 3-year RFS in the CapeOX group and the DS group was 67% vs. 75% (HR = 0.56, P =0.52), 43% vs. 42% (HR = 1.11, P =0.81), and 23% vs. 0% (HR = 1.59, P =0.39), respectively. Multivariable analysis adjusted for p stage showed no significant differences in RFS between the CapeOX group and the DS group (HR=1.06, P=0.85). Compared to DS, CapeOX was associated with lower incidences of febrile neutropenia (0% vs 7%) and alopecia (6% vs 74%), and a higher incidence of peripheral neuropathy (80% vs 23%). Conclusions: This analysis indicates that CapeOX and DS have comparable efficacy as adjuvant chemotherapy for p stage III GC in terms of RFS, albeit with different profiles of AEs.

Efficacy and safety of capecitabine and temozolomide (CAPTEM) in advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN): a systematic review and meta-analysis

Efficacy and safety of capecitabine and temozolomide (CAPTEM) in advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN): a systematic review and meta-analysis

Effectiveness and safety of capecitabine, irinotecan and panitumumab in advanced colorectal cancer.

Capecitabine, irinotecan, and panitumumab (CAPIRI-P) is a controversial regimen for metastatic colorectal cancer, with concerns regarding the efficacy and toxicity. However, its toxicity profile has been improved with dose reduction, and concerns regarding efficacy have been extrapolated from other trials. This retrospective study reports the real-world effectiveness and safety of modified CAPIRI-P (mCAPIRI-P). Advanced colorectal cancer patients receiving mCAPIPI-P in the first-line setting between July 2019 and December 2021 were analyzed. The progression-free survival on treatment (PFSOT) and overall survival (OS) were estimated using the Kaplan-Meier method, and the association with clinical and disease factors was analyzed using the Cox regression model. Serial changes in carcinoembryonic antigen (CEA) level and treatment toxicity were also evaluated. A total of 106 patients were included, of whom 97 (92%) and 31 (29%) had left-sided primary and unresectable liver-only disease, respectively. The median PFSOT and OS were 15.4 (95% CI 12.5-18.3) and 25.5 (95% CI 17.6-33.4) months, respectively. Sixteen (51.6%) and 10 (32.3%) liver-only disease patients underwent secondary liver treatment and R0 resection, respectively. In multivariable Cox regression, CEA responders (PFSOT: HR 0.53) and CEA normalization (PFSOT: HR 0.27; OS: HR 0.28) were independent favorable prognostic factors for PFSOT and OS. Grade ≥3 toxicity rate was 43%, mainly related to uncomplicated hematological toxicities. The real-world data show that mCAPIRI-P is safe and effective as the first-line treatment regimen for RAS wild-type advanced colorectal cancer and warrants further study.

＜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.

Safety and efficacy of irinotecan, oxaliplatin, and capecitabine (XELOXIRI) regimen with or without targeted drugs in patients with metastatic colorectal cancer: a retrospective cohort study

BackgroundFive-fluorouracil, folinic acid, oxaliplatin and irinotecan (FOLFOXIRI) regimen is used as the first-line treatment for metastatic colorectal cancer (mCRC). The use of capecitabine, an oral fluoropyrimidine pro-drug, is feasible and safe; hence, it provides an interesting alternative to 5-fluorouracil in the abovementioned regimen. This study aimed to evaluate the efficacy and safety of capecitabine, oxaliplatin, and irinotecan (XELOXIRI) regimen use with or without targeted drugs in Chinese patients with mCRC.MethodsWe conducted a retrospective, longitudinal cohort study of patients with mCRC who received XELOXIRI regimen with or without targeted drugs (bevacizumab or cetuximab) every 2 weeks between January 2017 and November 2019 at the National Cancer Center/Cancer Hospital, the Chinese Academy of Medical Sciences, and Peking Union Medical College. Treatment efficacy was assessed by investigators by evaluating the objective response rate (ORR) and disease control rate (DCR). Overall survival (OS) was assessed using Cox proportional hazards models. The adverse events were also analyzed.ResultsSixty-one consecutive patients were examined and followed up for survival. As of November 8, 2021, the median follow-up time was 35.4 months. Disease progression and death occurred in 50 (82%) and 38 (62%) patients, respectively. The median treatment duration of XELOXIRI with or without bevacizumab or cetuximab was 10 cycles (range, 1–12 cycles). The median OS and PFS were 32.2 months (95%CI [24.8–39.6]) and 9.3 months (95% CI [8.1–10.5]), respectively. The ORR of 48 patients with measurable lesions was 70.8%, and the DCR was 89.6%. RAS/BRAF wild-type (HR 0.39; 95% CI [0.16–0.96], p = 0.04) and metastatic organs > 2 (HR 3.25; 95% CI [1.34–7.87], p = 0.009) were independent prognostic factors for OS. The incidence of any grade of adverse events (AEs) was 96.7% (59/61). Grade ≥ 3 AEs included neutropenia (19.7%), leukopenia (9.8%), diarrhea (3.3%), vomiting (3.3%), febrile neutropenia (1.6%), and thrombocytopenia (1.6%). No treatment-related death occurred.ConclusionThe use of the XELOXIRI regimen with or without a targeted drug was effective, with a manageable toxicity profile in Chinese patients with mCRC.

A phase IB and randomised phase IIA trial of CApecitabine plus Radium-223 (Xofigo™) in breast cancer patients with BONe metastases: CARBON trial results

BackgroundApproximately 70% of patients with metastatic breast cancer (MBC) develop bone metastases. Despite advances in systemic treatment options and the use of bone targeted agents in the management of bone metastases to reduce skeletal morbidity, there remains an unmet need for further treatment options. Radium-223 (Ra223) is an alpha-emitting radiopharmaceutical that is preferentially taken up into bone at sites of increased osteoblastic activity where it emits high-energy, short-range alpha-particles that could provide a targeted anti-tumour effect on bone metastases. Here we evaluate the safety, feasibility and efficacy findings of the combination of Ra223 with capecitabine chemotherapy in patients with MBC with bone involvement. MethodsCARBON is a multi-centre, open-label phase IB/IIA study evaluating the combination of Ra223 (55 kBq/kg day 1 given on 6 weekly schedule) and capecitabine (1000 mg/m2 bd days 4–17 every 21 days) in patients with bone metastases from MBC (± other disease sites). Other eligibility criteria included ECOG performance status 0–2, ≤2 lines of chemotherapy for MBC and current bisphosphonate or denosumab use for ≥ 6 weeks. The phase IB part of the trial (6 patients) was conducted to provide preliminary feasibility and safety of capecitabine + Ra223. Thereafter, 28 patients were randomised (2:1) to capecitabine + Ra223 or capecitabine alone to further characterise the safety profile and evaluate efficacy, the primary efficacy endpoint being the bone turnover marker (urinary n-telopeptide of type I collagen) change from baseline to end of cycle 5 and secondary endpoints of time to first symptomatic skeletal event, and disease progression at extra-skeletal and bone disease. ResultsIn addition to bone metastases, 10/23 [44%] and 13/23 [57%] capecitabine + Ra223 and 2/11 [18%] and 9/11 [82%] capecitabine alone patients had soft tissue and visceral disease sites respectively. More capecitabine + Ra223 patients had received prior chemotherapy for MBC: 11/23 [48%] vs 2/11 [18%]. The analysis populations comprise 34 patients (23 capecitabine + Ra223, 11 capecitabine); 2 patients randomised to capecitabine + Ra223 received capecitabine alone and are included in the capecitabine arm. Median number of cycles received was 8.5 in capecitabine + Ra223 (range 3–12) and 12 in the capecitabine arm (range 1–12). 94/95 prescribed Ra223 cycles were administered. No dose limiting toxicities were seen in phase IB and no patients developed grade ≥ III diarrhoea. Gastrointestinal, haematological and palmer-planter erthyrodysesthesia adverse events were similar in both arms. Although formal statistical comparisons were not made, changes in bone turnover markers, the times to extra-skeletal progression and bone disease progression, and the frequency of symptomatic skeletal events were similar across the two treatment arms. ConclusionCapecitabine + Ra223 at the planned dose was safe and feasible in MBC patients with bone metastases. However, no efficacy signals were seen that might suggest greater efficacy of the combination over capecitabine alone clinically or biochemically.

Longitudinal efficacy and safety of capecitabine and cyclophosphamide as early-line treatment in patients with metastatic breast cancer: A prospective cohort study by the Kyushu Breast Cancer Study Group, Japan.

Longitudinal efficacy and safety of capecitabine and cyclophosphamide as early-line treatment in patients with metastatic breast cancer: A prospective cohort study by the Kyushu Breast Cancer Study Group, Japan.

511TiP A phase III, multicenter, open-label, randomized study to assess the efficacy and safety of cetuximab plus capecitabine versus cetuximab as maintenance treatment following first-line induction treatment with FOLFOX and cetuximab in Chinese patients with RAS and BRAF WT mCRC

Considering the efficacy and safety of capecitabine and cetuximab as potent agent for maintenance therapy from previous studies, evaluation on the efficacy of cetuximab in combination with capecitabine as a potential maintenance regimen for RAS and BRAF wild-type mCRC patients is warranted. This abstract describes the design of this study.

Definitive chemoradiotherapy for squamous cell carcinoma of the anal canal (SCCAC) with cisplatin and capecitabine: A prospective cohort—preliminary results.

e15506 Background: SCCAC is a rare disease. The standard care treatment with curative intent is chemoradiation with mitomycin (MMC) or cisplatin (CDDP) plus infusional 5-FU. Capecitabine may replace 5-FU in MMC doublet. However, MMC and infusional pumps are unavailable in many underdeveloped countries, and there is a lack of prospective data regarding the feasibility and safety of capecitabine combined with CDDP in definitive chemoradiotherapy. Methods: A Prospective cohort study aimed to evaluate the safety and efficacy of treatment with chemoradiation with CDDP60mg/m2 D1 and D29 plus capecitabine 825mg/m2/day BID in a population without MMC and infusional pump access. Eligible pts had T2-4/N0-3/M0 disease and were candidates to full curative CRT. Toxicity evaluation was the primary endpoint, secondary endpoint was response by RECIST v.1.1 at 8 weeks(w) and 6 months(m). The study data were prospectively collected using REDCap. Results: 23 pts were enrolled from Aug/2019 to Oct/2020 with a median follow-up of 7m. Median age 59 years; 76% (n=16) were stage III, 48% (n=11) were ECOG1, and 15% (n=3) were HIV+. All pts received concomitant radiotherapy, MVAT, with a median dose 54Gy in the primary tumor and 45Gy in elective nodes. At 8w, 18 patients were evaluable for response, 56% (n=10) had complete response (CR),39% (n=7) had partial response (PR) and 5% (n=1) progressive disease (PD). At 6 months 11 patients were evaluable for response, 64%(n=7) had CR, 18% (n=2) PR and 18% (n=2) PD. Any grade 3/4 toxicity was present in six pts, four of them radiodermatitis. The most frequent grade toxicities were nausea and radiodermatitis in all pts, anemia 81% (n=17), diarrhea 62% (n=13). Two older pts had definitive suspension of treatment due to toxicity. Three pts had hospitalization because of a skin infection. Six pts had disease recurrence, and two died by the cutoff date. One death related to diarrhea and vomiting toxicity in an older 84-year pt. OS and PFS are not reached. Conclusions: Definitive chemoradiotherapy with cisplatin and capecitabine is feasible; however, the older population is more vulnerable to treatment complications. Further prospective studies with a higher number of patients and longer follow up are required to evaluate SLP and OS.

Efficacy and safety of capecitabine and oxaliplatin (CAPOX) treatment in colorectal cancer: An observational study from a tertiary cancer center in South India.

">5-fluorouracil (5-FU) was the standard treatment care for colorectal cancer (CRC), however, its efficacy was limited due to safety concerns. Capecitabine and oxaliplatin (CAPOX) treatment was found equivalent to 5-FU in efficacy and preferred now due to easy management and convenience in administration. Hence, the present study aims to determine the efficacy and safety associated with CAPOX treatment in a real world non clinical setting. ">145 treatment-naive and newly diagnosed CRC patients were recruited in the study. Each patient received oxaliplatin 130 mg/m2 infusion over 2 hours on day 1 and oral capecitabine 1000 mg/m2 in divided doses twice daily for the next 14 days of a 21-day cycle. In the adjuvant setting, the observed disease-free survival rate was 62% (n=34) in the colon and 67% (n=15) in the rectum cancer patients at 2 years. The observed overall survival rate in the colon and rectal cancer was 80% (n=44) and 83% (n=18) respectively at 2 years. In the palliative setting the observed progression-free survival rate was 28% (n=13) in the colon and 33% (n=7) in rectal cancer patients at 2 years. The observed OSR at 2 years was 64% (n=30) in the colon and 67% (n=14) in the rectal cancer patients. Thrombocytopenia (17, 11.7%) and diarrhea (8, 5.5%) were the most commonly observed grade 3/4 hematological and gastrointestinal toxicities. Hand-foot syndrome and peripheral neuropathy were the major contributors for dose reduction (14, 9.6%), treatment delay (8, 5.4%), and drug discontinuation (9, 6.1%) in the study cohort. CAPOX treatment was found to be effective but associated with several dose-limiting toxicities.

Efficacy and Safety of Capecitabine Alone or in Combination in Advanced Metastatic Breast Cancer Patients Previously Treated with Anthracycline and Taxane: A Systematic Review and Meta-Analysis

Background: Capecitabine is frequently used alone or combined with other chemotherapy agents for the treatment of metastatic breast cancer in relapsed patients. Objective: The objective of this meta-analysis is to evaluate the effectiveness and safety of capecitabine monotherapy versus combination in the treatment of metastatic breast cancer patients pretreated with anthracycline and taxane. Methods: Eligible randomized controlled trials examining the efficacy and safety of capecitabine alone compared to capecitabine combination were systematically searched. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grades 3–4 drug-related adverse events were the outcomes assessed. Results: A total of 6,714 patients of 9 trials were involved in the pooled analysis. Our findings demonstrated that capecitabine combination is significantly superior to capecitabine monotherapy in improving PFS (hazard ratio [HR] 1.32, 95% CI 1.13–1.54, p < 0.0001) and ORR (risk ratio [RR] 0.67, 95% CI 0.54–0.83, p < 0.001), but it was insignificant in OS (HR 1.09, 95% CI 0.98–1.22, p = 0.12). On the other hand, the incidence of non-hematological adverse events such as hand-foot syndrome and diarrhea was lower in capecitabine combination compared to capecitabine monotherapy. Conclusion: Capecitabine-based combination chemotherapy showed superiority over capecitabine monotherapy in terms of PFS and ORR, with no significant difference in OS. Non-hematological adverse effects such as hand-foot syndrome were fewer with a combination regimen. However, hematological adverse events were fewer with capecitabine monotherapy regimen.

Effect of Reduced-Dose Capecitabine Plus Cetuximab as Maintenance Therapy for RAS Wild-Type Metastatic Colorectal Cancer

Fluorouracil-based chemotherapy combined with anti-epidermal growth factor receptor/vascular endothelial growth factor therapy is the standard first-line treatment for metastatic colorectal cancer followed by low-intensity maintenance therapy to balance the clinical efficacy and adverse effects (AEs). However, there have been concerns about the AEs of capecitabine plus cetuximab as a maintenance therapy in patients with RAS wild-type metastatic colorectal cancer. To evaluate the biological activity and safety of capecitabine plus cetuximab as a novel maintenance therapy for RAS wild-type metastatic colorectal cancer. This phase 2 prospective clinical trial was conducted from April 29, 2016, to April 29, 2019, at 5 centers in China. Patients diagnosed as having RAS wild-type metastatic colorectal cancer were recruited to receive fluorouracil-based cytotoxic agents combined with cetuximab followed by capecitabine plus cetuximab for maintenance therapy. Forty-seven patients with histologically confirmed metastatic colorectal cancer and genetic test results showing a wild-type RAS were enrolled in maintenance therapy. Induction therapy for patients with RAS wild-type metastatic colorectal cancer was 8 to 12 cycles of fluorouracil-based chemotherapy combined with cetuximab. After stable disease status or better was achieved, reduced-dose capecitabine plus cetuximab was administered for maintenance therapy. The primary end point was progression-free survival during maintenance therapy. The secondary end points were total progression-free survival, overall survival, quality of life, safety, and toxic effects of treatment. Forty-seven patients were enrolled in maintenance therapy, with a median age of 52 years (range, 25-81 years) and 32 (68%) of them being men. The median maintenance progression-free survival was 7.2 (95% CI, 5.8-8.6) months. The median progression-free survival was 12.7 (95% CI, 11.8-15.4) months. The median overall survival was 27.4 (95% CI, 21.4-35.5) months. Grade 3 to 4 AEs during induction therapy included neutropenia (4 patients [9%]), diarrhea (4 patients [9%]), nausea or vomiting (3 patients [6%]), rash acneiform (10 patients [21%]), and hand-foot syndrome (8 patients [17%]). Grade 3 to 4 AEs during maintenance therapy included diarrhea (2 patients [4%]), rash acneiform (8 patients [17%]), and hand-foot syndrome (5 patients [11%]). Reduced-dose capecitabine plus cetuximab after initial chemotherapy is a novel maintenance therapy for patients with RAS wild-type metastatic colorectal cancer that achieved good outcomes and tolerable nonserious AEs. ClinicalTrials.gov Identifier: NCT02717923.

Capecitabine and cisplatin as a second-line chemotherapy for patients with advanced biliary tract cancer.

543 Background: Few data are available on second-line chemotherapy for patients with advanced biliary tract cancer. We retrospectively analyzed the efficacy and safety of capecitabine and cisplatin combination as second-line chemotherapy for advanced biliary tract cancer. Methods: Between Mar, 2014 and Dec, 2018, advanced BTC patients who received second-line capecitabine and cisplatin after the failure of the gemcitabine-platinum combination were analyzed. Progression‐free survival (PFS) and overall survival (OS) were estimated with the Kaplan‐Meier method. Cox models were used for multivariate analyses. Results: Of total 40 patients, male: female was 24(60%) to 16(40%), and the median age was 68 years old (range: 45-77) . As primary tumor site, 8(20%) was intrahepatic, 16(40%) was extrahepatic and 16(40%) was gallbladder. Initially metastatic disease was 22(55%), and recurrent disease after curative surgery was 17(42.5%) and locally advanced unresectable disease was 1(2.5%). 30(75%) patients had ECOG performance status of 0-1. The mean number of the chemotherapy cycles was 3.3 ± 2.0. Objective response rates and stable disease were 12.5% and 25%, respectively. Median PFS and median OS from the beginning of the capcitabine and cisplatin combination were 2.8 and 7.0 months, respectively. Grade 3-4 adverse event were neutropenia (n = 7, 17.5%), anemia(n = 3, 7.5%), hand-foot syndrome (n = 3, 7.5%), nausea and vomiting(n = 2, 5%), peripheral neuropathy (n = 2, 5%) and mucositis(n = 1, 2.5%). And there was no treatment related death. Conclusions: This study showed the possible survival benefit of capecitabine and cisplatin combination as second-line chemotherapy for advanced biliary tract cancer.

Phase II study of capecitabine plus oxaliplatin (CapOX) as adjuvant chemotherapy for locally advanced rectal cancer (CORONA II)

ObjectiveThis multicenter, single-arm phase II study (UMIN000008429) aimed to evaluate the efficacy and safety of capecitabine plus oxaliplatin (CapOX) as postoperative adjuvant chemotherapy for patients with locally advanced rectal cancer.MethodsPatients with resectable clinical Stage II or III rectal cancer were enrolled to receive eight cycles of CapOX therapy (130 mg/m2 oxaliplatin on day 1 and 2000 mg/m2 oral capecitabine on days 1–14, every 3 weeks) after curative surgical resection. The primary endpoint was 3-year relapse-free survival (RFS) rate, and secondary endpoints were 3-year overall survival (OS) rate, treatment compliance, and safety.ResultsA total of 40 patients (Stage II, 21; Stage III, 19) were enrolled between September 2012 and November 2015 from seven institutions. Thirty-nine patients (97%) received R0 resection, and 32 patients (84%) received postoperative CapOX therapy. The completion rate of all eight cycles of CapOX therapy was 66%. Relative dose intensities were 87% for oxaliplatin and 84% for capecitabine. At a median follow-up period of 46 months, disease recurrence was observed in nine patients, including three with local recurrence. Three-year RFS and OS rates were 75% (95% CI 57–86%) and 96% (95% CI 80–99%), respectively. Frequencies of Grade ≥ 3 hematological and non-hematologic adverse events were 19% and 38%, respectively.ConclusionCapOX therapy is feasible as adjuvant chemotherapy for locally advanced rectal cancer.

Capecitabine in patients with platinum-pretreated advanced or recurrent cervical carcinoma: a retrospective study.

Cervical cancer is a common malignancy among women and, when recurring, presents a dismal prognosis. After platinum failure, second-line treatments report response rates ranging from 3-15%, a median progression-free survival of about 3 months and a median overall survival of about 5.5 months.To retrospectively evaluate the activity and safety of capecitabine in patients with advanced/recurrent cervical carcinoma.MethodsA retrospective review of medical records of recurrent cervical cancer patients, who had failed a previous platinum-paclitaxel treatment and received oral capecitabine 1250 mg/m2 twice daily continuously from day 1 to day 14 every 21 days, was performed from December 2013 to March 2018 at the Gynecologic Oncology Unit of the Fondazione IRCCS National Cancer Institute of Milan, Italy. The response rate was evaluated every three cycles according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Common Terminology Criteria for Adverse Events version 4.0 were used to evaluate adverse events. We retrospectively analyzed 35 patients with recurrent cervical carcinoma, treated with oral capecitabine. All patients had previously received and failed a combination of carboplatin plus paclitaxel as first-line therapy for advanced/recurrent disease. Median age at the first capecitabine administration was 53 years (range 27-82). All patients were evaluable for response: the overall response rate was 34.2% (2.8% complete responses and 31.4% partial responses) with a clinical benefit rate of 57% (overall response rate plus 22.8% stabilizations of disease). The most common grade 1-2 adverse events per patient were fatigue (71.3%), hand-foot syndrome (57.0%), diarrhea (31.3%), constipation (17.0%), and nausea (10.4%). Only three patients (8.5%) reported grade 3 adverse events. Our data suggest that oral capecitabine should be considered an active and safe treatment in patients with recurrent cervical carcinoma after platinum failure. Based on these results, we consider capecitabine as warranting further clinical evaluation.

Evaluation of capecitabine in patients with platinum-pretreated advanced or recurrent cervical carcinoma: A retrospective study of the IRCCS National Cancer Institute of Milan.

5535Background: Cervical cancer is underrepresented in the gynecological clinical research. The objective of this retrospective study was to evaluate the activity and the safety of capecitabine in ...