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Grade 3/4 toxicities including neutropenia, thrombocytopenia, diarrhea, hand-foot-syndrome (grade 2/3), and neurosensory effects (fixed-effect models). Cap, capecitabine; FU, fluorouracil; OR, odds ratio.
Source publication
Six randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX.
This analysis compared all published CAP/OX versus infusional FU/OX regimens....
Context in source publication
Context 1
... grade2/3 hand-foot-syndrome (HFS; HR 3.54; 95% CI, 2.07 to 6.05; P .00001) were significantly less prominent in the FU-based regimens, with all intertrial variability consistent with the play of chance (Fig 5). However, with respect to severe diarrhea and, moreover, neutropenia, the findings of major heterogeneity between trials (P .009 ...
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Capecitabine, a 5-fluorouracil prodrug, has been integrated into the management of multiple cancer types. In order to obtain information about plasma levels of capecitabine in patients who had drug intake at home during chemotherapy, a simple HPLC method for capecitabine monitoring has been developed and validated.
Capecitabine levels were quantifi...
There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer (MBC) in older Chinese patients.
MBC patients aged > 65 years pretreated...
A retrospective analysis was conducted to compare the tolerability and efficacy of single-agent capecitabine and 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) in the first-line treatment of patients aged > or =65 years with metastatic colorectal cancer (mCRC).
Consecutive patients with mCRC treated at the Military Medical Institute, Warsaw, betwee...
Rationale:
Capecitabine (CAP) is a chemotherapeutic agent used to treat breast and gastrointestinal cancers. The most common adverse reactions of CAP primarily included gastrointestinal and dermatological effects. Whereas, the CAP-induced fatty liver had never been reported.
Patient concerns:
In this study, a-69-year old female presented a histo...
A phase III trial (Cancer and Leukemia Group B CALGB-49907) was conducted to test whether older patients with early-stage breast cancer would have equivalent relapse-free and overall survival with capecitabine compared with standard chemotherapy. The quality of life (QoL) substudy tested whether capecitabine treatment would be associated with a bet...
Citations
... CAPOX is reported to have signi cant higher grade 3-4 thrombocytopenia than FOLFOX (3-12% vs. 1-6%) (14). However, the negative effect of thrombocytopenia induced by CAPOX has not been paid enough attention. ...
Background: Adjuvant CAPOX (capecitabine plus oxaliplatin) provided significant disease-free survival (DFS) benefit in patients with high-risk stage II or stage III colorectal cancer (CRC). Conventional triweekly CAPOX results in 14-38% 3-4 grade hematological toxicity. Modified biweekly CAPOX was observed to be generally well-tolerated in previous studies.
Methods: High-risk stage II and stage III post-surgery CRC patients were randomized in the control triweekly group (intravenous infusion of oxaliplatin 130 mg/m2 on day 1 and oral capecitabine 1000 mg/m2, twice daily from d1 to d14) and the experimental biweekly group (intravenous infusion of oxaliplatin 85 mg/m2 on day 1 and oral capecitabine 1000 mg/m2, twice daily from d1 to d10). The primary endpoint was incidence of thrombocytopenia. The secondary endpoint was 18-month DFS rate.
Results: Between Jul 25, 2018, and May 14, 2021, 160 patients were 1:1 randomly enrolled and received treatment. The primary endpoint thrombocytopenia occurred 33% and 49% in biweekly and triweekly group (P=0.02). The second endpoint 18-month DFS in 3-month group was 94.1% in biweekly CAPOX group, and 93.8% in triweekly CPOX group (P=0.96). Neutropenia was 36% and 51% in biweekly and triweekly group, respectively (P=0.04). The rate of uncomplete therapy patient was 7% and 15% in biweekly and triweekly group, respectively (P=0.13).
Conclusion: Biweekly CAPOX presented significant less thrombocytopenia and neutropenia than triweekly CAPOX regimen. And biweekly CAPOX did not affect the 18-month DFS rate.
Clinical trial registration: First registration date: 21/06/2018. ClinicalTials.gov (NCT03564912).
... 14 In studies using biweekly 48-h infusional 5-FU, the incidence of grade 2-3 HFS is usually <10%. 15 No studies have been carried out on the outcome of HFS in patients who switched to this schedule after experiencing severe capecitabine-induced HFS. In a recent phase III study in patients with metastatic CRC comparing trifluridinee tipiracil with capecitabine, both plus bevacizumab, treatment with trifluridineetipiracil was associated with less all-grade HFS (1% versus 53%) but with more hematological adverse events. ...
Background:
Fluoropyrimidines (FPs) are an essential part of the majority of systemic regimens in the treatment of metastatic colorectal cancer (CRC). The use of the oral FP S-1 has been approved by the European Medicines Agency as monotherapy or in combination with oxaliplatin or irinotecan, with or without bevacizumab, for the treatment of patients with metastatic CRC in whom it is not possible to continue treatment with another FP due to hand-foot syndrome (HFS) or cardiovascular toxicity (CVT). Subsequently, this indication has been included in the 2022 ESMO guidelines for metastatic CRC. Recommendations for use in daily practice are not available.
Patients and methods:
Based on peer-reviewed published data on the use of S-1 in Western patients with metastatic CRC who switched from infusional 5-fluorouracil (5-FU) or capecitabine to S-1 for reasons of HFS or CVT, recommendations for its use were formulated by an international group of medical oncologists with expertise in the treatment of metastatic CRC and a cardio-oncologist.
Results:
In patients who experience pain and/or functional impairment due to HFS during treatment with capecitabine or infusional 5-FU, a switch to S-1 is recommended without prior dose reduction of capecitabine/5-FU. S-1 should preferably be initiated at full dose when HFS has decreased to grade ≤1. In patients with cardiac complaints, in whom an association with capecitabine or infusional 5-FU treatment cannot be excluded, capecitabine/5-FU should be discontinued and a switch to S-1 is recommended.
Conclusions:
These recommendations should guide clinicians in daily practice in the treatment of patients with metastatic CRC with FP-containing regimens.
... The combination of capecitabine plus oxaliplatin (XELOX) compared to infusional 5-fluorouracil, leucovorin plus oxaliplatin (FOLFOX) has shown similar response rate, progression-free survival, and overall survival in several phase III clinical trials [1]. The safety of the two regimens differs considerably as 5-fluorouracil, leucovorin plus oxaliplatin (FOLFOX) is associated with higher grade 3 and 4 neutropenia/ granulocytopenia and febrile neutropenia while capecitabine plus oxaliplatin (XELOX) is associated relatively more with grade 3 diarrhoea and grade 3 hand-foot syndrome [3,4]. Also, the administration of capecitabine plus oxaliplatin (XELOX) does not involve continuous infusions and hence it´s an attractive option for limited-resource settings. ...
... Hospital: the reported incidence of grade 3 and 4 adverse events was relatively low due to several reasons including the retrospective nature of the study that compromised the reporting and grading of common adverse events as well as the attrition rate of patients that did not receive six or more cycles of capecitabine plus oxaliplatin. With regards to the safety of capecitabine plus oxaliplatin regimen in our cohort, the findings rhymed with reports from two large meta-analyses were the incidence of grade 3 and 4 thrombocytopenia, as well as grade 3 and 4 hand-foot syndrome was high in capecitabine plus oxaliplatin group [3,4]. Neuropathy is a well-documented side effect of oxaliplatin with a rate of 64% in several centres in South Africa. ...
Introduction:
a capecitabine and oxaliplatin drug combination regimen has shown a survival benefit in patients with advanced colorectal cancer, yet its administration represents an attractive option for low resource settings. This study aimed to describe the therapeutic utility, efficacy and safety of a capecitabine plus oxaliplatin drug combination in patients with colorectal cancer.
Methods:
a review of medical records of sixty adult patients with histological diagnosis of colorectal cancer at Tygerberg Hospital between June 2012 and June 2017 was conducted. The overall response rate was assessed after a three cycle regime of capecitabine and oxaliplatin with the progression-free survival (PSF) results estimated using the Kaplan-Meier methods.
Results:
among the 60 participants identified over the study period, the median age was 53 years with 45% being female (n=27). Records showed that 58.33% of patients had the colon as the primary site and 68.33% of patients had synchronous liver metastases at presentation. On average, all patients received 6 cycle regimes of capecitabine and oxaliplatin. Sixty percent of the patients received this treatment regime with palliative intent while in the radical-intent group, equal numbers of patients received the regime as either neoadjuvant or adjuvant. A liver resection was also performed in 20 patients (31.8%). The overall response rate was 69.6% with 13 patients attaining a complete response. Disease progression was reported in 30.4% and the 1-year progression free survival was 44.5% (95% CI: 0.31-0.57) while the 2-year progression free survival was 25.1% (95% CI: 0.14-0.38). Regarding safety, thrombocytopenia was the most frequent adverse event (18.5%) and overall, 15.1% of patients experienced grade 3 and 4 toxicity.
Conclusion:
a drug combination of capecitabine and oxaliplatin showed a good overall response rate and survival particularly in patients with resectable colorectal liver metastases.
... A meta-analysis aiming to compare CAPEOX and FOLFOX included six randomized controlled trials. Although the dose and infusion mode of the FOLFOX evolution regimens were different in the six trials, no significant difference was noted between PFS and OS (35). The difference noted in the FOLFOX evolution regimens was mainly interrelated to the incidence of adverse reactions, suggesting that researchers and clinicians should seek the lowest point of DI and adverse reactions on the premise of maintaining survival benefits. ...
... The difference noted in the FOLFOX evolution regimens was mainly interrelated to the incidence of adverse reactions, suggesting that researchers and clinicians should seek the lowest point of DI and adverse reactions on the premise of maintaining survival benefits. CAPEOX and FOLFOX have shown approximate efficacy in multiple large clinical trials and improved benefits were demonstrated in combination with Bev (35,36). The two regimens are a combination of 5-FU and L-OHP and the difference is mainly reflected in the incidence of adverse reactions. ...
Chemotherapy dose intensity is a momentous parameter of antitumor clinical medication. In certain clinical trials, the actual application dose of the chemotherapeutic drugs is frequently different from the prescribed dose. The chemotherapy dose intensity completed in different trials is also variable, which has an impact on the treatment efficacy, disease prognosis and patient safety. When these agents are tested in the population, chemotherapy reduction and delay or failure to complete the planned cycle constantly occur due to age, performance status, adverse reactions and other reasons, resulting in the modification of the chemotherapy dose intensity. The present review analyzed the correlation between the chemotherapy dose intensity and the incidence of adverse reactions, the treatment efficacy and disease prognosis in clinical trials of metastatic colorectal cancer. Moreover, the clinical applications of chemotherapy dose intensity were discussed. Based on individual differences, the present review analyzed the clinical trials that examined the efficacy of the chemotherapy dose intensity in different patient populations. The conclusions suggested that different populations require a specific dose intensity to reduce treatment toxicity without affecting the curative effect.
... To improve prognosis, adjuvant chemotherapy is applied. Combinatorial therapy of several anticancer drugs can significantly prolong the survival of patients with stage III-IV CRC [105]. The mainstream approaches in first-line treatment use combinatorial therapies which include FOLFIRI (folinic acid and 5fluorouracil with irinotecan), CAPOX (capecitabine and oxaliplatin), and FOLFOX (folinic acid, 5-fluorouracil and oxaliplatin) [106]. ...
The Wnt/β-catenin signaling pathway has been implicated as the central mechanism that drives colorectal carcinogenesis. Its activation is historically due to mutation on APC (adenomatous polyposis coli), resulting to nuclear localization of β-catenin and expression of Wnt target genes that promote tumor progression. Although this pathway seems to be a pivotal therapeutic target because of its critical role in colorectal cancer, there has been no clinically approved therapies targeting Wnt/β-catenin signaling pathway to this date. Here, we reviewed the recent progress of this signal transduction pathway in colorectal tumorigenesis. Apart from their roles in cancer initiation, the new pathway modulators (activators and repressors) also participate in chemoresistance, epithelial-mesenchymal transition and cancer stem cell renewal. Of the proteins reported to modulate this pathway, CDX2 (Caudal-related homeobox transcription factor 2) showed potentials as promising molecular target. CDX2 warrants further studies to determine its significance as molecular target for colorectal cancer therapeutics. Overall, the regulation of Wnt/β-catenin signaling pathway remains intriguingly complex and is not fully understood in spite of the widespread research efforts. Its intricacy remains a major barrier in the development of chemotherapeutic agent that specifically targets it.
... Capecitabine in combination with oxaliplatin (XELOX) as a first-line therapy for mCRC showed similar efficacy and safety to FOLFOX [64]. However, identification of a capecitabine plus irinotecan (XELIRI) regimen with a favorable tolerability profile has proven to be difficult. ...
Opinion statement
Intravenous administration of fluoropyrimidine-based chemotherapy has been the backbone of treatment in colorectal cancer (CRC) for decades. The availability of oral capecitabine has improved the tolerability and simplified combination schedules. In addition to capecitabine, several other oral drugs have proven efficacy, particularly in palliative treatment lines. Clinical guidelines describe several available third-line treatment options for metastatic CRC (mCRC), but few insights are provided to guide the selection and sequence. In this review, we describe the available evidence and most recent data concerning oral drugs with proven efficacy in CRC, including antiangiogenetic tyrosine kinase inhibitors (VEGFR TKIs), inhibitors blocking EGFR/Raf/MEK/ERK signaling pathway and modified fluoropyrimidine, and share recommendations and insights on selecting third-line oral therapies for mCRC in China. In general, third-line treatment options for mCRC are mainly regorafenib, fruquintinib, and chemo/targeted therapy reintroduction, while FTD/TPI was rarely used in China probably due to poor accessibility. Fruquintinib is preferred in patients with poor performance status (PS), elder age, and severe organ dysfunction, compared to regorafenib. New drugs of clinical trials were more recommended for the patients with BRAF mutant tumor, and those with good previous treatment efficacy tended to be recommended for chemo/targeted therapy reintroduction. The management of mCRC is evolving, and it must be emphasized that the consideration and recommendations presented here reflect current treatment practices in China and thus might change according to new clinical data as well as the availability of new oral drugs.
... Therefore, doublet therapy is the treatment regimen of choice. As doublet therapy with capecitabine and oxaliplatin (CAPOX), 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), and 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) have similar efficacy, all are incorporated in the present study protocol 46,53,54 . ...
Background
A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC.
Methods
This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life.
Discussion
This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections.
... The cost-minimization method is the most adequate, since the literature indicated that the effectiveness of the treatment regimens is equivalent. 5,6,[8][9][10] The variables collected for the study population (clinical and sociodemographic characteristics) were extracted from the institution's electronic records. The following inclusion criteria were adopted: patient aged 18 years or older; diagnosed with malignant colon neoplasm and/or rectosigmoid and/or rectal junction by the International Classification of Diseases (ICD) codes C10 -C18, C19 or C20, respectively; with a procedure from the High Complexity Procedure Authorization (Autorização ...
Objective: To conduct a pharmacoeconomic evaluation between XELOX and mFOLFOX6 in the adjuvant and metastatic treatment of colorectal cancer from the perspective of a public reimbursement hospital. Methods: The cost minimization analysis was conducted for patients who started treatment in 2013 and 2014. The micro-costing technique was used to verify expenditures on drugs, materials, laboratory and imaging tests, ambulatory and daily hospitalization, human and administrative resources and determine the individual cost of each alternative, per patient. To evaluate the robustness of the economic analysis, multivariate sensitivity analysis was performed in six different scenarios. Results: There was an average cost for XELOX of U$ 4,637.14 in adjuvant and U$ 3,831.48 for palliative treatment, and a cost for mFOLFOX6 of U$ 5,474.89 in adjuvant and U$ 4,432.95 in palliative treatment. Sensitivity analysis maintained the dominance of XELOX. Material and drug costs accounted for about 85% of the total cost of XELOX; for mFOLFOX6 this cost was around 36%. On the other hand, the cost of hospitalization and placement of a catheter occured exclusively for mFOLFOX6, which also presented a higher cost with human resources. Conclusion: From the perspective of the hospital, XELOX proved to be the least costly alternative on the treatment of colorectal cancer.
... and was shorter than in published randomised clinical trials for CAPOX regimen (7.1-10.3 months for CA-POX in first-line treatment; 4.7 months for CAPOX in second-line treatment) [3,4]. The reason for the differ-ence between our results and data from clinical trials is uncertain, but it is probably due to patient selection for randomised trials. ...
... Median OS in the study population was 16.9 months (95% CI, 14.9-18.8). This value is similar to the results obtained in randomised clinical trials, in which (depending on the study) it was from 16.0 to 24.6 months, average 17-19 months [3,4]. In one study with use of CAPOX regimen in second-line treatment the median OS was 11.9 months, compared to 14.2 months (95% CI, 11.3-17.0) in an analogous group in our population [6]. ...
... The chemotherapy chosen was based on prior data showing the feasibility of CRT with capecitabine with or without oxaliplatin and the proven similar efficacy of fluorouracil (5FU) and capecitabine as single agent in adjuvant colon cancer. [8][9][10][11][12][13][14][15] ...
Purpose:
The PETACC 6 trial investigates whether the addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative capecitabine improves disease-free survival (DFS) in locally advanced rectal cancer.
Methods:
Between November 2008 and September 2011, patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node positive, were randomly assigned to 5 weeks preoperative capecitabine-based chemoradiation (45-50.4 Gy) followed by six cycles of adjuvant capecitabine, both without (control arm, 1) or with (experimental arm, 2) oxaliplatin. The primary end point was improvement of 3-year DFS by oxaliplatin from 65% to 72% (hazard ratio [HR], 0.763).
Results:
A total of 1,094 patients were randomly assigned (intention to treat), and 1,068 eligible patients started their allocated treatment (arm 1, 543; arm 2, 525), with completion of protocol treatment in 68% (arm 1) v 54% (arm 2). A higher rate of grade 3/4 adverse events was reported in the experimental arm (14.4% v 37.3% and 23.4% v 46.6% for neoadjuvant and adjuvant treatment, respectively). At a median follow-up of 68 months (interquartile range, 58-74 months), 157 and 156 DFS events were observed in arms 1 and 2, respectively (adjusted HR, 1.02; 95% CI, 0.82 to 1.28; P = .835). Three-year DFS rate was not different, with 76.5% (95% CI, 72.7% to 79.9%) in arm 1, which is higher than anticipated, and 75.8% (95% CI, 71.9% to 79.3%) in arm 2. The 7-year DFS and overall survival (OS) rates were not different as well, with DFS of 66.1% v 65.5% (HR, 1.02) and OS of 73.5% v 73.7% (HR, 1.19) in arms 1 and 2, respectively. Subgroup analyses revealed heterogeneity in treatment effect according to German versus non-German site location, without detectable confounding factors in multivariable analysis.
Conclusion:
The addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative adjuvant chemotherapy impairs tolerability and feasibility and does not improve efficacy.
