Capecitabine-based Chemotherapy Research Articles

Management of patients with reduced dihydropyrimidine dehydrogenase activity receiving combined 5-fluoruracil-/capecitabine-based chemoradiotherapy.

5‑Fluoruracil (5-FU) and its oral prodrug capecitabine are mainstays in combined chemoradiotherapy regimens. They are metabolized by dihydropyrimidine dehydrogenase (DPYD). Pathogenic variants of the DPYD gene cause areduction in DPYD activity, leading to possibly severe toxicities. Therefore, patients receiving 5‑FU-/capecitabine-based chemoradiotherapy should be tested for DPYD variants. However, there are limited clinical data on treatment adjustments and tolerability in patients with decreased DPYP activity receiving combined chemoradiotherapy. Therefore, aretrospective analysis of the toxicity profiles of patients with decreased DPYD activity treated at our center was conducted. For all patients receiving 5‑FU-/capecitabine-based chemo(radio)therapy at our department, DPYD activity was routinely tested. Genotyping of four DPYD variants (DPYD*2A, DPYD*13, c.2846A > T, and haplotype B3) was conducted according to the recommendation of the German Society for Hematooncology (DGHO) using TaqMan hydrolysis polymerase chain reaction (PCR; QuantStudy3, Thermo FisherScientific, Darmstadt). DPYD variants and activity score as well as clinical data (tumor entity, treatment protocol, dose adjustments, and toxicity according to the Common Terminology Criteria for Adverse Events [CTCAE]) were assessed and reported. Of 261 tested patients, 21exhibited DPYD variants, 18of whom received chemoradiotherapy. All but one patient was treated for rectal or anal carcinoma. The observed rate of DPYD variants was 8.0%, and heterozygous haplotype B3 was the most common (5.75%). One patient exhibited ahomozygous DPYD variant. DPYD activity score was at least 0.5in heterozygous patients; chemotherapy dose was adjusted accordingly, with an applied dose of 50-75%. CTCAE grade2 skin toxicity (50%) and grade3 leukopenia (33.3%) were most common. One patient experienced atransient grade4 increase in transaminases. All high-grade toxicities were manageable with supportive treatment and transient. No CTCAE grade5 toxicities related to 5‑FU administration were observed. With dose reduction in heterozygous patients, toxicity was within the range of patients without DPYD variants. Our clinical data suggest that dose-adapted 5‑FU-/capecitabine-chemoradiotherapy regimens can be safely considered in patients with heterozygous clinically relevant DPYD variants, but that the optimal dosage still needs to be determined to avoid both increased toxicity and undertreatment in acurative setting.

A multicenter, prospective, non-interventional real-world study to assess the effectiveness of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal cancer.

Mecapegfilgrastim, a long-actinggranulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or thefluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

Treatment Response and Survival with Chemotherapy for Unresectable, Nonmetastatic Cholangiocarcinoma.

Limited studies have dwelt upon the treatment of unresectable, nonmetastatic cholangiocarcinoma as a separate entity. Hence, the management protocols are not clearly defined for this subgroup of patients. We aimed to analyze patients treated for unresectable, nonmetastatic cholangiocarcinoma. We analyzed the treatment of patients with unresectable, nonmetastatic cholangiocarcinoma retrospectively. A total of 162 cases of cholangiocarcinoma were reported to our center from 2016 to 2019, out of which 54 were unresectable and nonmetastatic. Thirty patients opted for treatment and were the subjects of this study. Of 30 patients, 24 had hyperbilirubinemia, out of which 10 received chemotherapy after biliary drainage procedure. Out of 30 patients, a total of 16 patients had received chemotherapy, while 14 did not. Gemcitabine/Cisplatin was the first-line chemotherapy administered to 9 patients, whereas 5 received Gemcitabine/Capecitabine and 2 received single-agent gemcitabine. Partial response was documented in 6 patients, and 4 patients had stable disease. The median overall survival was 12.04 months in patients who had received chemotherapy and 6.02 months in those who did not receive chemotherapy (p = 0.005). The median progression-free survival was 6.53 months for patients who had received chemotherapy. The aHR for mortality with chemotherapy compared with no chemotherapy was 0.353 (95% CI: 0.154-0.807). The study data demonstrate that gemcitabine combined with cisplatin- or capecitabine-based chemotherapy prolongs survival in patients with unresectable and nonmetastatic cholangiocarcinoma. In patients with cholangiocarcinoma associated with jaundice, biliary drainage procedure enables giving chemotherapy. Hyperbilirubinemia persisting despite drainage procedures portends poor prognosis and represents an unmet need. Gupta A, Sahai P, Prasad M, et al. Treatment Response and Survival with Chemotherapy for Unresectable, Nonmetastatic Cholangiocarcinoma. Euroasian J Hepato-Gastroenterol 2024;14(1):5-8.

Clinicopathologic Profile and Treatment Outcomes of Colorectal Cancer in Young Adults: A Multicenter Study From India.

Colorectal cancer (CRC) in young adults is a rising concern in developing countries such as India. This study investigates clinicopathologic profiles, treatment patterns, and outcomes of CRC in young adults, focusing on adolescent and young adult (AYA) CRC in a low- and middle-income country (LMIC). A retrospective registry study from January 2018 to December 2020 involved 126 young adults (age 40 years and younger) with CRC. Patient demographics, clinical features, tumor characteristics, treatment modalities, and survival outcomes were analyzed after obtaining institutional ethics committees' approval. Among 126 AYA patients, 62.70% had colon cancer and 37.30% had rectal cancer. Most patients (67%) were age 30-39 years, with no significant gender predisposition. Females had higher metastatic burden. Abdominal pain with obstruction features was common. Adenocarcinoma (65%) with signet ring differentiation (26%) suggested aggressive behavior. Limited access to molecular testing hindered mutation identification. Capecitabine-based chemotherapy was favored because of logistical constraints. Adjuvant therapy showed comparable recurrence-free survival in young adults and older patients. For localized colon cancer, the 2-year median progression-free survival was 74%, and for localized rectal cancer, it was 18 months. Palliative therapy resulted in a median overall survival of 33 months (95% CI, 18 to 47). Limited access to targeted agents affected treatment options, with only 27.5% of patients with metastatic disease receiving them. Chemotherapy was generally well tolerated, with hematologic side effect being most common. This collaborative study in an LMIC offers crucial insights into CRC in AYA patients in India. Differences in disease characteristics, treatment patterns, and limited access to targeted agents highlight the need for further research and resource allocation to improve outcomes in this population.

A Nomogram to Predict Severe Toxicity in DPYD Wild-Type Patients Treated With Capecitabine-Based Anticancer Regimens.

DPYD-guided dosing has improved the safety of fluoropyrimidine-based chemotherapy in recent years. However, severe toxicity remains in ~ 23% of patients not carrying DPYD variant alleles treated with capecitabine. Therefore, we developed a predictive model based on patient-related and treatment-related factors aimed at estimating the risk of developing severe capecitabine-related toxicity. The nomogram was developed using data from two large clinical trials (NCT00838370 and NCT02324452). Patients with cancer carrying a DPYD variant allele (DPYD*2A, c.1236G>A, c.2846A>T, and c.1679T>G) were excluded. Univariable and multivariable logistic regression using predetermined predictors based on previous findings, including age, sex, body surface area, type of treatment regimen, and creatinine levels were used to develop the nomogram. The developed model was internally validated using bootstrap resampling and cross-validation. This model was not externally or clinically validated. A total of 2,147 DPYD wild-type patients with cancer treated with capecitabine-based chemotherapy regimens were included of which complete data of 1,745 patients were available and used for the development of the nomogram. Univariable and multivariable logistic regression showed that age, sex, and type of treatment regimen were strong predictors of severe capecitabine-related toxicity in DPYD wild-type patients. Internal validation demonstrated a concordance index of 0.68 which indicates a good discriminative ability for prediction of severe capecitabine-related toxicity. The developed nomogram includes readily available parameters and may be a helpful tool for clinicians to assess the risk of developing severe capecitabine-related toxicity in patients without known risk DPYD variant alleles treated with capecitabine-based anticancer regimens.

Capecitabine-based chemotherapy in early-stage triple-negative breast cancer: a meta-analysis

IntroductionThe efficacy and safety of adjuvant capecitabine in early-stage triple-negative breast cancer remains undefined. A meta-analysis was conducted to elucidate whether capecitabine-based regimens could improve survival in early-stage triple-negative breast cancer (TNBC).MethodsThe current study searched Medline, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov proceedings up to 2023.9. Disease-free survival (DFS), overall survival (OS), and grade 3–4 adverse events (AEs) were assessed. Extracted or calculated hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled.ResultsThe capecitabine-based regimens showed significant advantages in DFS (HR = 0.81, 95% CI: 0.73–0.90; P <.001) and OS (HR = 0.75, 95% CI: 0.65–0.87; P <.001) from 12 randomized controlled trials (RCTs) with 5,390 unselected participants. Subgroup analysis of DFS showed analogous results derived from patients with lymph node negative (HR = 0.68, 95% CI: 0.50–0.92; P = .006) and capecitabine duration no less than six cycles (HR = 0.73; 95% CI: 0.62-0.86; P <.001). Improvement of DFS in the addition group (HR = 0.77, 95% CI: 0.68–0.87; P <.001) and adjuvant setting (HR = 0.79, 95% CI: 0.70–0.89; P <.001) was observed. As to safety profile, capecitabine was associated with more frequent stomatitis (OR = 5.05, 95% CI: 1.45–17.65, P = .011), diarrhea (OR = 6.11, 95% CI: 2.12–17.56; P =.001), and hand–foot syndrome (OR = 31.82, 95% CI: 3.23–313.65, P = .003).ConclusionsAdjuvant capecitabine-based chemotherapy provided superior DFS and OS to early-stage TNBC. The benefits to DFS in selected patients with lymph node negative and the addition and extended duration of capecitabine were demonstrated.

Neoadjuvant chemoradiotherapy with capecitabine based regimen in locally advanced rectal cancer: A retrospective study.

Capecitabine-based neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer. The objective of this study is to analyze overall survival (OS), disease-free survival (DFS) and prognostic factors of patients with stage II to III rectal cancer treated with nCRT in our institution. Between March 2014 to June 2020, 121 locally advanced rectal cancer patients were retrospectively reviewed and analyzed. All of the enrolled patients were treated with capecitabine-based nCRT (pelvic radiotherapy: 45-50.4 Gy, 1.8 Gy/d plus concomitant capecitabine-based chemotherapy), total mesorectal excision surgery (surgery was carried out 8-12 weeks after the end of CRT), and capecitabine-based adjuvant chemotherapy. We examined the pathological complete response rate, 3-year OS, 3-year DFS and the other prognostic factors. Kaplan-Meier method and Log-rank test were used to estimate and compare survival rate. With a median follow-up of 36 months, 3-year DFS and 3-year OS was 74.4% and 83.2%, respectively. Among the 121 patients, 24 achieved pathological complete remission (19.8%). After multivariate analysis, ypTNM stage (TNM stage after neoadjuvant therapy) was significantly associated with DFS. Positive mesorectal fasciae (MRF) status on magnetic resonance imaging and ypTNM stage were significantly related to OS. CRT with capecitabine based regimen provides high rates of survival and sphincter preservation with acceptable toxicity. YpTNM stage was significantly associated with DFS; magnetic resonance imaging MRF status and ypTNM stage were significant factors for OS after multivariate analysis. Distant metastasis is the dominant mode of treatment failure, and it is crucial to optimize systemic treatment for newly diagnosed patients.

Differential benefit of capecitabine-based chemotherapy among TNBC subtypes in the context of the CBCSG010 study.

528 Background: Our previous study classified TNBCs into four mRNA subtypes, provided additional insights into TNBC heterogeneity and potential therapeutic options. Then we conducted a phase Ib/II subtyping-based and genomic biomarker-guided umbrella trial (FUTURE, NCT03805399 ), demonstrated the clinical benefit of subtyping-based targeted therapy for refractory metastatic TNBC. Here, we further evaluate the prognosis and predictive value of molecular classification in early TNBC in CBCSG010 trial (NCT01642771), which is a prospective, randomized phase III trial confirmed adding capecitabine to anthracycline-taxane-based adjuvant chemotherapy significantly improved survival in TNBC. Methods: Tumor tissues and pathological sections were retrospectively collected. Immunohistochemical (IHC) staining and hematoxylin and eosin (HE) staining were performed on paraffin-embedded sections to conduct TNBC IHC subtype staining. RNA-sequencing were performed to characterize the intrinsic molecular features of TNBC microenvironment. Results: 585 patients enrolled in the CBCSG010 trial, 450 patients had pathological sections, among which 207 patients achieved successfully stained sections. PDL1, CD8 and stromal tumor infiltrating lymphocytes (sTILs) were chosen for identified TNBC Immune enriched phenotype. Patients with ≥20% positive tumor cell proportion score (TPS) of PDL1, ≥10% positive cells of CD8, and ≥10% positive sTILs were significantly associated with better 5y-DFS (disease-free survival). Among Immune enriched TNBC, kaplan-Meier curves showed that DFS rates were 96.4% and 73.7% in the capecitabine and control groups. Transcriptome data was used to picture the immune microenvironment landscape, showed that “immune-hot” patients (immune cells or immune genes enriched) were more likely to benefit from capecitabine treatment. Conclusions: TNBC subtypes is significantly associated with DFS, with Immune enriched phenotype achieving the best outcome, and “immune-hot” patients are more likely to benefit from adjuvant capecitabine. Designing future clinical trials adding immunotherapy in adjuvant treatment of TNBC might base on molecular features.

CLO23-027: Do Proton Pump Inhibitors Affect the Effectiveness of Capecitabine-Based Chemotherapy in Colorectal Cancers? A Systematic Review With Meta-Analysis

"CLO23-027: Do Proton Pump Inhibitors Affect the Effectiveness of Capecitabine-Based Chemotherapy in Colorectal Cancers? A Systematic Review With Meta-Analysis" published on 31 Mar 2023 by National Comprehensive Cancer Network.

Influence of Single-Nucleotide Polymorphisms on Clinical Outcomes of Capecitabine-Based Chemotherapy in Colorectal Cancer Patients: A Systematic Review.

The aim of this systematic review was to provide a comprehensive overview of the literature published in the last decade on the association of single-nucleotide polymorphisms in genes involved in the pharmacodynamic and pharmacokinetic pathways of capecitabine with treatment outcomes among colorectal cancer patients. A systematic search of the literature published in the last 10 years was carried out in two databases (Medline and Scopus) using keywords related to the objective. Quality assessment of the studies included was performed using an assessment tool derived from the Strengthening the Reporting of Genetic Association (STREGA) statement. Thirteen studies were included in this systematic review. Genes involved in bioactivation, metabolism, transport, mechanism of action of capecitabine, DNA repair, and folate cycle were associated with toxicity. Meanwhile, genes related to DNA repair were associated with therapy effectiveness. This systematic review reveals that several SNPs other than the four DPYD variants that are screened in clinical practice could have an impact on treatment outcomes. These findings suggest the identification of future predictive biomarkers of effectiveness and toxicity in colorectal cancer patients treated with capecitabine. However, the evidence is sparse and requires further validation.

Risk factors for fluoropyrimidine-induced cardiotoxicity in colorectal cancer: A retrospective cohort study and establishment of a prediction nomogram for 5-FU induced cardiotoxicity.

Fluoropyrimidine is an important component of systemic chemotherapy for colorectal cancer (CRC). Fluoropyrimidine-induced cardiotoxicity (FIC) may result in delay and discontinuation of chemotherapy and, in severe cases, can even be life-threatening. To date, risk factors for FIC have not been well identified. This cohort study aimed to identify the predictors of FIC in CRC patients and develop a risk prediction nomogram model. Between January 1, 2018 and December 31, 2020, colorectal cancer patients who received 5-fluoropyrimidine(5-Fu)/capecitabine-based chemotherapy in Affiliated Cancer Hospital of Guizhou Medical University were included. FIC was defined as an adverse cardiovascular event related to fluoropyrimidine that occurred during or within four weeks of completing chemotherapy. Risk factors were determined by LASSO algorithm and multivariate logistic regression analysis. Nomogram for predicting 5-Fu-induced cardiotoxicity was established and internally validated. The concordance index (C-index) and calibration curve were used to evaluate the nomogram's discrimination and accuracy. A total of 916 patients were included for analysis, and 200 [21.8%,95% confidence interval (CI):19.12%-24.47%] experienced FIC. LASSO algorithm and multivariate logistic regression analysis determined that chemotherapy ≤3 cycles (OR=4.694, 95%CI=3.184-6.92), age≥ 60 (OR=1.678, 95%CI=1.143-2.464), BMI>22.97 (OR=1.77, 95%CI=1.202-2.606), and simultaneous use of bevacizumab (OR=2.922, 95%CI=1.835-4.653) were significant risk factors, and were included in the prediction model for 5-Fu induced cardiotoxicity. The C-index (95%CI) was 0.751 (0.706-0.795) by internal validation. For patients treated with capecitabine-based regimen, the incidence of FIC increased with the absolute value of neutrophils (OR=5.177, 95%CI=1.684-15.549) and eosinophils (OR=3.377,95% CI=1.237-9.22). Our study identified risk factors for FIC and established a prediction nomogram model based on chemotherapy cycle, age, BMI and use of target therapy for 5-FU induced Cardiotoxicity. The discriminative prediction model can be used for patient counselling and risk-stratification before undergoing chemotherapy in colorectal cancer.

T-DXd Keeps Shining in Breast Cancer.

The latest phase III data from DESTINY-Breast02 and DESTINY-Breast03 indicate that trastuzumab deruxtecan, or T-DXd, outperforms capecitabine-based chemotherapy and T-DM1 in patients with metastatic HER2-positive breast cancer. According to results from an investigator-initiated trial, TRIO-US B-12 TALENT, T-DXd may also have neoadjuvant potential in HER2-low disease.

Initiation of the Pharmacogenetics of Capecitabine in Morocco

Introduction: The pharmacogenetics of anticancer drugs is of paramount importance in minimizing their side effects and increasing their efficacy. When applied to capecitabine, the result is that variation in patient responses has been largely linked to different genetic polymorphisms of dihydropyrimidine dehydrogenase (DPD), which explained in many cases, the onset of toxicity of this medication in patients. Failure of this enzyme is known to be responsible for a high incidence of serious or fatal side effects. In this study conducted on Moroccan patients under treatment with capecitabine at usual doses at the Fez University Hospital, the first in Africa and Morocco, we are looking for the presence of four variants of the DPD gene (DPYD): T486A on exon 5 (rs666523971), c.1679T> G (p.I560S; rs55886062; allele DPYD * 13) on exon 13, c.1905 + 1G> A (IVS14 + 1G> A; rs3918290; allele DPYD * 2A) on the splice site near exon 14 and the c.2846A> T mutation (p.D949V; rs67376798) on exon 22. We will therefore seek to establish the cause-and-effect relationship between this toxicity and the presence of these variants in his patients, which will allow us to avoid the dangerous prescription of capecitabine in patients carrying these polymorphisms. Methods: This prospective study is carried out at the Laboratory of Medical Genetics of the CHU Hassan II Fez and spread over a period of 3 years. Patient recruitment was carried out by the oncology department of CHU Hassan II-Fès. All recruited patients are treated with capecitabine. A total of 64 patients were tested. Blood samples (5 ml) were obtained from each one of them after their consent, and DNA was extracted. The study of these four polymorphisms was carried out by PCR sequencing. Results and Discussion: We have studied 64 patients taking capecitabine. Their median age was 50, and the mean age was 50 and 79, with extremes of 25 and 78 years. The sex ratio F / M was 0,60. Different levels of toxicity have been developed in patients ranging from simple vomiting to IVdegree hand and foot syndrome and second-degree neuropathy involving total discontinuation of treatment. These mutations were not found in the patients. Thus it would be interesting to enlarge the sample size, look for these polymorphisms and others on other exons of the DPYD gene, and try to understand the cause of this increased incidence of capecitabine toxicity in the Moroccan population. Conclusion: Capecitabine-based chemotherapy caused adverse effects with varying levels in its patients. The SNPs on the DPYD gene sought were not found in this Moroccan sample. It is desirable to screen more patients and to search for other SNPs to understand the toxicity of capecitabine in relation to the DPYD gene. This will make it possible to adjust the dosage of this drug, increase its effectiveness and minimize its toxicity.

The prognosis and risk factors for capecitabine maintenance treatment in metastatic breast cancer: a retrospective comparative cohort study.

BackgroundMaintenance treatment following efficient chemotherapy can improve the treatment outcomes of patients with metastatic breast cancer (MBC). However, there are no studies for identifying the prognostic factors for patients who could benefit from capecitabine maintenance. Therefore, this study aimed to investigate the prognosis and risk factors of capecitabine maintenance therapy and analysed the circulating tumour DNA (ctDNA) markers that may be related to the treatment response.MethodsThis study recruited 482 consecutive patients with MBC who achieved clinical benefit from capecitabine-based chemotherapy from 2011 to 2019. A total of 256 patients received subsequent capecitabine maintenance therapy. The baseline clinical factors included age at diagnosis, menopause, neoadjuvant therapy, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and subtypes, prior treatment lines, and prior capecitabine-based treatment response. Treatment outcome (progression-free survival, PFS) was assessed by imaging tools according to RSCIST 1.1 standard during the first two treatment cycles and every 3 weeks thereafter. Univariate and multivariate Cox proportional hazards models were used to analysethe association between capecitabine maintenance treatment and prognosis.ResultsThe median PFS of patients receiving capecitabine maintenance treatment was 21.7 months [95% confidence interval (CI): 15.1–36.3 months]. Capecitabine maintenance showed similar effects as endocrine maintenance or anti-HER2 therapy in hormone receptor (HR)-positive or HER2-positive patients, with adjusted HR of 1.17 (95% CI: 0.81–1.71, P=0.40). In patients with triple-negative breast cancer (TNBC), capecitabine maintenance showed a marginal benefit in PFS. Compared to late-line (≥2) capecitabine maintenance, first-line capecitabine maintenance significantly prolonged median PFS. Compared to other HR/HER2 subtypes, patients with HR-positive and HER2-positive subtypes significantly benefited from capecitabine maintenance treatment. Analysis of ctDNA revealed that among patients receiving capecitabine maintenance, TP53 aberrations were concentrated in patients with short PFS.ConclusionsCapecitabine maintenance treatment is associated with longer PFS in patients with MBC, especially those receiving first-line capecitabine-based chemotherapy and those with HR positivity/HER2 positivity. TP53 aberrations may be responsible for the poor response to capecitabine maintenance treatment.

Addition of Capecitabine to Adjuvant Chemotherapy May be the Most Effective Strategy for Patients With Early-Stage Triple-Negative Breast Cancer: A Network Meta-Analysis of 9 Randomized Controlled Trials.

Background and ObjectivePrevious studies determined the therapeutic effects of capecitabine-based chemotherapy regimens on early-stage triple-negative breast cancer (TNBC). However, the optimal strategy of capecitabine-based chemotherapy remains uncertain. We conducted this network meta-analysis to address this issue.MethodsWe systematically searched PubMed, Embase, and the Cochrane Registry of Controlled Trials (CENTRAL) to retrieve eligible studies published before September 2021. Two independent reviewers extracted information from eligible studies using a pre-designed data extraction sheet. The primary outcome included disease-free survival, and the second outcome showed overall survival and adverse events. Direct meta-analysis was performed using RevMan 5.4, and Bayesian network analysis was performed using R version 3.6.1 with the “gemtc” and “rjags” packages.ResultsNine studies involving 3661 TNBC patients met the selection criteria. The network meta-analysis suggested that the addition of capecitabine to adjuvant chemotherapy achieved a significantly longer disease-free (HR = 0.66, 95% CrI = 0.49 to 0.86) and overall survival time (HR = 0.60, 95% CrI = 0.43 to 0.83) than standard chemotherapy. All comparisons did not achieve statistical significance. The addition of capecitabine to adjuvant chemotherapy was the most effective treatment for improving disease-free (81.24%) and overall survival (78.46%) times, and the replacement of capecitabine to adjuvant chemotherapy was the safest regime.ConclusionsBased on available evidence, capecitabine-based chemotherapy benefits TNBC patients, and the addition of capecitabine with adjuvant chemotherapy was the most effective regime. In contrast, the replacement of capecitabine to adjuvant chemotherapy was the safest regime. More studies of high quality and large scale are needed to confirm our findings.

Six cases of appendiceal cancer: Literature review, diagnosis and treatment

Appendiceal cancer is a very rare disease. Based on 6 cases of appendiceal cancer who were admitted to the Internal Medicine of Breast, Gastroenterology, Hepatology, Urology, Department, Oncology Hospital of Ho Chi Minh City from September 2019 to March 2021, we evaluate the available literature review about diagnosis and treatment of appendiceal cancer. Four out of 6 cases were diagnosed with stage IV disease, only 1 case was in stage II, and 1 case with undermined stage. All cases were treated with Capecitabine-based chemotherapy, 5 out of 6 were treated with Capecitabine and Oxaliplatin combination, while the other was treated with Capecitabine monotherapy. We didn’t use hyperthermic intraperitoneal chemotherapy in any of those cases because of technical limitations at Ho Chi Minh City Oncology Hospital. Up to the time of reporting, all 6 cases are being monitored for survival.

Milk and Egg Are Risk Factors for Adverse Effects of Capecitabine-Based Chemotherapy in Chinese Colorectal Cancer Patients.

Background:Chemotherapy-induced adverse effects (CIAEs) remain a challenging problem due to their high incidences and negative impacts on treatment in Chinese colorectal cancer (CRC) patients. We aimed to identify risk factors and predictive markers for CIAEs using food/nutrition data in CRC patients receiving post-operative capecitabine-based chemotherapy.Methods:Food/nutrition data from 130 Chinese CRC patients were analyzed. Univariate and multivariate analyses were used to identify CIAE-related food/nutrition factors. Prediction models were constructed based on the combination of these factors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the discrimination ability of models.Results:A total of 20 food/nutrition factors associated with CIAEs were identified in the univariate analysis after adjustments for total energy and potential confounding factors. Based on multivariate analysis, we found that, among these factors, dessert, eggs, poultry, and milk were associated with several CIAEs. Most importantly, poultry was an overall protective factor; milk and egg were risk factors for hand-foot syndrome (HFS) and bone marrow suppression (BMS), respectively. Developed multivariate models in predicting grade 1 to 3 CIAEs and grade 2/3 CIAEs both had good discrimination (AUROC values from 0.671 to 0.778, 0.750 to 0.946 respectively), which had potential clinical application value in the early prediction of CIAEs, especially for more severe CIAEs.Conclusions:Our findings suggest that patients with high milk and egg intakes should be clinically instructed to control their corresponding dietary intake to reduce the likelihood of developing HFS and BMS during capecitabine-based chemotherapy, respectively.Trial registration:ClinicalTrials.gov Identifier: NCT03030508.

Development of a New Tool to Assess the Quality of Life of Patients with Hand-Foot Syndrome Receiving Capecitabine-Based Therapy: A Pilot Study.

Prathepa JagdishBackground Hand–foot syndrome (HFS) can result in significant deficits in health-related quality of life (HRQOL) and can lead to poor compliance, dose reduction, or interruption. This study was performed to assess the HRQOL with HFS on physical, psychological, social, and sexual aspects of patients receiving capecitabine-based chemotherapy with gastrointestinal cancer along with validating and assessing the reliability score of the questionnaire. Patients and Methods HFS-related QOL (HF-QOL) questionnaire was developed and validated in a sample of 30 patients randomly selected for this pilot study. The internal consistency of the tool was tested by calculating the Cronbach's α coefficient, while content and construct validity were assessed by Pearson's correlation. Statistical analyses were performed using SPSS version 25.0. Results Out of 30, 22 (73%) patients were males, mean age was 44 ± 13 years; 21 (70%) patients had grade 1 HFS, while 6 (20%) and 3 (10%) patients had grades 2 and 3 HFS, respectively. Cronbach's α coefficient was high for physical (0.79) and sexual scales (0.79), while it was moderately low for psychological (0.65) and social (0.53) domains. The average HF-QOL scores were 70.6 ± 13.2 in physical domain and 71.3 ± 23.7 in sexual domain indicating poor quality of life (QOL), while it was 50.9 ± 9.9 in social domain indicating moderately worse QOL. Grades 2 and 3 of HFS were found to have statistical significance on physical (0.0001), psychological (0.05), and social (0.02) domains, whereas sexual domain did not have any statistical significance (0.594). Conclusion This pilot study showed the feasibility of use and validity of a new patient-reported instrument, the HF-QOL, which measures the effect of HFS on daily activities (physical, psychological, social, and sexual domains) after capecitabine-based chemotherapy.

Outcomes of Patients Living With HIV and Anal Cancer Treated With Definitive Intensity-Modulated Radiation Therapy and 5-Fluorouracil- or Capecitabine-Based Chemotherapy

To assess outcomes after definitive chemo-irradiation in HIV patients with anal cancer, and evaluate hemato-immunologic (HI) toxicity by dynamics of CD4+ cell counts and lymphocytes and their association with the dose received by active bone marrow (ABM).Patients treated for anal cancer with HIV infection at a single institution between 2007-2020 were identified. Characteristics were tabulated along with CD4+ cell counts and lymphocytes ranging from before treatment to length of follow-up. Dose to ABM was derived by overlaying the bone contours and 3D dose matrix on a pre-treatment PET/CT scan using deformable registration. Parts of the bone with greater than the mean PET standardized uptake value (SUV) in the bone were designated as ABM. Differences in HI parameters over time points were compared using Wilcoxon rank sum tests; risk of recurrence, overall survival (OS) and progression-free survival (PFS) were modeled using Kaplan-Meier methods.A total of 44 patients with anal cancer and HIV were identified, of which 7 had detectable HIV viral load pre-treatment. Radiation was most commonly 50.4-54 Gy via IMRT; 3 patients underwent RT alone. Chemotherapy was 5-fluorouracil+mitomycin (n = 27), Capecitabine+mitomycin (n = 11), or other (n = 3). With median follow-up 59 months (range: 5-164) there were 7 loco-regional recurrences, 2 distant metastases and 9 deaths. The 2- and 5-year OS for patients with stage I/II disease was 100% and 93.3% vs. 88.1% and 66.6% for stage III, the 2- and 5-year PFS were both 93.8% for stage I/II disease vs. 76.5% and 56.7% for stage III. Outcomes with 5FU vs. capecitabine were comparable with 2-year OS of 92.3% and 90.9% (P = 0.89) and PFS of 77.4% and 90.9% (P = 0.26). CD4 counts dropped from a pre-treatment median of 320 cells/ul to 101 at nadir (after ∼3 months), to 163 at 1 year and 214 at 2 years post IMRT. Lymphocyte counts changed from 1,600 per ul to 400 at nadir, to 1,200 and 1,400 at 1 and 2 years. Patients with distant or locoregional recurrence showed trends (P < 0.10) of worse recovery of HI toxicity at 1 and 2 years (Table 1). Median mean ABM dose was 33.7 Gy (range: 20.2-40.3 Gy) and median V15Gy and V40Gy were 91% (range: 58-99%) and 39% (range: 0-62%). No association was found between ABM dose and dynamics of HI toxicity, possibly due to relatively high ABM doses for all patients.Outcomes after definitive chemo-IMRT were promising with excellent OS and PFS in this vulnerable patient group, with no difference when substituting 5-fluorouracil for capecitabine. There was some acute HI toxicity with worse recovery in patients who experienced disease recurrence and strategies to better spare ABM including dose de-escalation are ongoing.

Spermine-Related DNA Hypermethylation and Elevated Expression of Genes for Collagen Formation are Susceptible Factors for Chemotherapy-Induced Hand-Foot Syndrome in Chinese Colorectal Cancer Patients.

Hand-foot syndrome (HFS) is a common capecitabine-based chemotherapy-related adverse event (CRAE) in patients with colorectal cancer (CRC). It is of great significance to comprehensively identify susceptible factors for HFS, and further to elucidate the biomolecular mechanism of HFS susceptibility. We performed an untargeted multi-omics analysis integrating DNA methylation, transcriptome, and metabolome data of 63 Chinese CRC patients who had complete CRAE records during capecitabine-based chemotherapy. We found that the metabolome changes for each of matched plasma, urine, and normal colorectal tissue (CRT) in relation to HFS were characterized by chronic tissue damage, which was indicated by reduced nucleotide salvage, elevated spermine level, and increased production of endogenous cytotoxic metabolites. HFS-related transcriptome changes of CRT showed an overall suppressed inflammation profile but increased M2 macrophage polarization. HFS-related DNA methylation of CRT presented gene-specific hypermethylation on genes mainly for collagen formation. The hypermethylation was accumulated in the opensea and shore regions, which elicited a positive effect on gene expression. Additionally, we developed and validated models combining relevant biomarkers showing reasonably good discrimination performance with the area under the receiver operating characteristic curve values from 0.833 to 0.955. Our results demonstrated that the multi-omics variations associated with a profibrotic phenotype were closely related to HFS susceptibility. HFS-related biomolecular variations in CRT contributed more to the relevant biomolecular mechanism of HFS than in plasma and urine. Spermine-related DNA hypermethylation and elevated expression of genes for collagen formation were closely associated with HFS susceptibility. These findings provided new insights into the susceptible factors for chemotherapy-induced HFS, which can promote the implementation of individualized treatment against HFS.