Capecitabine-based Chemotherapy Research Articles

CDA and MTHFR polymorphisms are associated with clinical outcomes in gastroenteric cancer patients treated with capecitabine-based chemotherapy.

The impact of pharmacogenetics on predicting survival in gastroenteric cancer remains unclear. We tested 322 consecutive patients treated with capecitabine-based chemotherapy for CDA and MTHFR polymorphisms. Patients who carried the CDA 79 A>C (rs2072671) CC genotype showed significantly shorter progression-free survival (PFS) comparing with A-allele (P = 0.008). A significant better PFS was found in the patients with 451 A>G (rs532545) G-allele (P = 0.002) and 92 C>T (rs602950) T-allele (P = 0.002). In addition, a shorter PFS was also observed in patients with MTHFR 1298 A>C (rs1801131) CC genotype than the patients with AC or AA genotype after capecitabine-based chemotherapy (P = 0.002). Furthermore, the colon, female, or elder (> 65years old) patients with MTHFR 1298 A>C CC genotype had poorer PFS than A-allele. Moreover, CDA 451 A>G was independent predictors of chemotherapy-induced toxicity in colon patients. Multivariate Cox regression analysis demonstrated that the CDA 79 A>C CC, 451 A>G AA, 92 C>T CC, and MTHFR 1298 A>C CC were predictive of shorter PFS in gastroenteric cancer patients. The results reminded us those gastroenteric cancer patients with CDA 79 A>C CC, 451 A>G AA, 92 C>T CC, or MTHFR 1298 A>C CC genotype are not likely to benefit from the therapy of capecitabine-based chemotherapy.

The prognostic impact of consensus molecular subtypes (CMS) and its predictive effects for bevacizumab benefit in metastatic colorectal cancer: molecular analysis of the AGITG MAX clinical trial

The consensus molecular subtypes (CMS) is a transcriptome-based classification of colorectal cancer (CRC) initially described in early-stage cohorts, but the associations of CMS with treatment outcomes in the metastatic setting are yet to be established. This study aimed to evaluate the prognostic impact of CMS classification and its predictive effects for bevacizumab benefit in metastatic CRC by correlative analysis of the AGITG MAX trial. The MAX trial previously reported improved progression-free survival (PFS) for the addition of bevacizumab (B) to chemotherapy [capecitabine (C)±mitomycin (M)]. Archival primary tumours from 237 patients (50% of trial population) underwent gene expression profiling and classification into CMS groups. CMS groups were correlated to PFS and overall survival (OS). The interaction of CMS with treatment was assessed by proportional hazards model. The distribution of CMS in MAX were CMS1 18%, CMS2 47%, CMS3 12%, CMS4 23%. CMS1 was the predominant subtype in right-sided primary tumours, while CMS2 was the predominant subtype in left-sided. CMS was prognostic of OS (P = 0.008), with CMS2 associated with the best outcome and CMS1 the worst. CMS remained an independent prognostic factor in a multivariate analysis. There was a significant interaction between CMS and treatment (P-interaction = 0.03), for PFS, with hazard ratios (95% CI) for CB+CBM versus C arms in CMS1, 2, 3 and 4: 0.83 (0.43-1.62), 0.50 (0.33-0.76), 0.31 (0.13-0.75) and 1.24 (0.68-2.25), respectively. This exploratory study found that CMS stratified OS outcomes in metastatic CRC regardless of first-line treatment, with prognostic effects of CMS groups distinct from those previously reported in early-stage cohorts. In CMS associations with treatment, CMS2 and possibly CMS3 tumours may preferentially benefit from the addition of bevacizumab to first-line capecitabine-based chemotherapy, compared with other CMS groups. Validation of these findings in additional cohorts is warranted. This is a molecular sub-study of MAX clinical trial (NCT00294359).

The Effect of Telephone-Based Follow-Up on Adherence, Efficacy, and Toxicity of Oral Capecitabine-Based Chemotherapy.

Background:Adherence and safety challenges aroused with the use of oral chemotherapeutic agents, such as capecitabine, necessitated implementation of a more focused follow-up for patients receiving these agents.Patients and Methods:This prospective, randomized open-label study explored the usefulness of weekly telephone-based follow-up in Egyptian patients with metastatic colorectal or gastric cancer treated with capecitabine-based chemotherapy regimens at the National Cancer Institute, Egypt, compared with a standard care group. Patients' adherence, safety, efficacy, and health service utilization were assessed and compared in 82 eligible patients; control group (n = 38) and intervention group (n = 44).Results:The intervention group showed statistically better tolerability to certain adverse effects in certain cycles with nonsignificantly higher patients' adherence and overall survival (OS), along with statistically higher passive call duration.Conclusion:These results suggested that pharmacist-led telephone follow-up (TFU) could help in building a close trusting rapport between the patient and caregiving pharmacist. They also demonstrated the potential usefulness of the TFU on patients' tolerability, adherence, and OS; however, further trials with a larger sample size should be encouraged to explore more pronounced results. Otherwise, the provided standard care could be considered good enough for these patients.

Association Between Serum Folate Level and Toxicity of Capecitabine During Treatment for Colorectal Cancer.

Folate level was proposed to be a predictor for fluoropyrimidine-related toxicity. We conducted a prospective study to determine the association between serum and red-cell folate and capecitabine-related toxicity in patients with colorectal cancers. Eligibility criteria included diagnosis of colorectal cancers; eligible patients who were scheduled to undergo capecitabine monotherapy or capecitabine-oxaliplatin (CAPOX) for adjuvant or palliative purposes. Exclusion criteria included concomitant radiotherapy or chemotherapy other than capecitabine or CAPOX and creatinine clearance <30 mL/min. Fasting serum and red-cell folate were measured prior to chemotherapy. Capecitabine was administered at 2,500 mg/m2 per day (monotherapy) or 2,000 mg/m2 per day (CAPOX) for 14 days every 3 weeks. The toxicity of the first four cycles was documented by clinical investigators who were blinded to folate levels. A total of 144 patients were recruited, of whom 126 were eligible; 40 patients had capecitabine alone, and 86 patients received CAPOX. The rates of grade 2 and grade 3 toxicity were 63.5% and 14.3%, respectively. Nausea and vomiting were the most common grade ≥2 adverse event (47.7%), followed by hand-foot syndrome (25.4%), diarrhea (23.1%), and neutropenia (22.3%). Combination with oxaliplatin (odds ratio [OR], 2.77; p = .043) and serum folate (OR, 10.33; p = .002) were independent predictors of grade ≥2 toxicity. Red-cell folate was not predictive of toxicity. For every 10 nmol/L increment in serum folate, the risk of grade ≥2 toxicity increased by 9%. Serum folate level, but not red-cell folate, was associated with higher rate of grade ≥2 toxicity during capecitabine-based treatment. Excessive folate intake may be avoided before and during capecitabine-based chemotherapy. This is the first prospective study to evaluate the association between serum folate level and capecitabine-related toxicity in patients with colon cancers. It shows that higher serum folate level is associated with increased risks of moderate to severe toxicity during capecitabine-based treatment. Excessive folate intake should be avoided before and during capecitabine-based chemotherapy.

Cardiotoxicity of 5-fluorouracil and capecitabine in Chinese patients: a prospective study

Background5-Fluorouracil (5-FU) and capecitabine-associated cardiotoxicity ranging from asymptomatic electrocardiography (ECG) abnormalities to severe myocardial infarction has been reported in a number of studies, but such cardiotoxicity in Chinese patients with malignant diseases has not been investigated to date. In the present study, we aimed to prospectively evaluate the incidence rates and clinical manifestations of 5-FU- and capecitabine-associated cardiotoxicity in cancer patients recruited from multiple centers in China.MethodsAmong the 527 patients who completed the study, 196 received 5-FU-based chemotherapy and 331 received capecitabine-based chemotherapy as either first-line or adjuvant therapy. Adverse events were reported during the treatment and up to 28 days of follow-up. Outcome measures included ECG, myocardial enzymes, cardiac troponin, brain natriuretic peptide and echocardiography. Univariate analysis and logistic regression were performed for subgroup analysis and identification of significant independent variables that are associated with cardiotoxicity of both agents.ResultsIn total, 161 of 527 patients (30.6%) experienced cardiotoxicity. The incidence rate of cardiotoxicity was 33.8% (112/331) in the capecitabine group, which was significantly higher than the rate of 25% (49/196) in the 5-FU group (P = 0.0042). 110/527 patients (20.9%) suffered arrhythmia, 105/527 (19.9%) developed ischemic changes, while only 20/527 patients (3.8%) presented heart failure and 6/527 patients (1.1%) had myocardial infarction. Pre-existing cardiac disease, hypertension, capecitabine-based chemotherapy and duration of treatment were identified as significant risk factors associated with cardiotoxicity. The odds ratio were 15.7 (prior history of cardiac disease versus no history), 1.86 (capecitabine versus 5-FU), 1.06 (5–8 versus 1–4 chemotherapy cycles) and 1.58 (hypertension versus no hypertension), respectively.ConclusionsCardiotoxicity induced by fluoropyrimidines in the Chinese population may be underestimated in clinical practice. Close monitoring of patients is recommended, especially for those patients at high risk for cardiotoxicity. Possible risk factors are duration of treatment, capecitabine-based chemotherapy, pre-existing cardiac diseases and hypertension.Trial registration This study was initiated on January 22, 2014 and has been retrospectively registered with the registration number ChiCTR1800015434

Polymorphisms in the ICOS/CD28-ICOSL pathway are related to capecitabine-based chemotherapy response in advanced colon cancer patients

Polymorphisms within a gene’s 3′-UTR may modulate posttranscriptional regulation of gene expression, and may explain individual sensitivity of chemotherapy. To investigate the correlation between single nucleotide polymorphisms (SNPs) in 3′-UTRs of B7/CD28 family genes and the response of capecitabine-based chemotherapy in colon cancer, 16 SNPs were identified in 274 advanced colon cancer patients. Statistical analysis indicated that ICOS rs1559931, rs4404254, and rs4675379 were in complete linkage disequilibrium and significantly associated with chemotherapy response. Heterozygous patients with rs1559931 G/A (31.34% vs 48.29%; P = 0.016), rs4404254 T/C (30.43% vs 48.77%; P = 0.011), or rs4675379 G/C (28.13% vs 49.04%; P = 0.004) genotypes showed poorer response to chemotherapy compared to wildtype patients. Moreover, three SNPs, including ICOSL rs15927, ICOSL rs3804033 and CD28 rs3181113, were significantly associated with the occurrence of side effects of chemotherapy. In addition, patients with ICOSL rs15927 G/G (78.26%), ICOSL rs3804033 G/G (76.00%), or CD28 rs3181113 T/T (82.05%) were more prone to enduring adverse events compared to patients bearing other polymorphisms. Taken together, our findings demonstrated that polymorphisms in the 3′-UTRs of genes in the ICOS/CD28-ICOSL pathway may influence the efficacy and occurrence of adverse events of capecitabine-based chemotherapy in advanced colon cancer patients.

Clinical outcome for continuous versus intermittent chemotherapy for unresectable metastatic colorectal cancer: Comparative analysis after first-line therapy.

825 Background: Colorectal cancer (CRC) is the third most common and second most lethal cancer in the U.S, with almost 50% of patients developing metastatic disease. Although survival of metastatic CRC (mCRC) has improved significantly, current treatment strategies are associated with many adverse effects. With no prospect of cure, goals of treatment should consider both quantity and quality of life. Interruption of chemotherapy after induction can represent a means to achieve this balance. Methods: The primary objective of this meta-analysis is to assess the effect of continuation vs interruption of systemic therapy in terms of survival in patients with unresectable mCRC after first line treatment. Among 15 prospective studies published from 2009-2017, 9 qualified for inclusion. Random-effect model was used for pooled effects within two main categories: continuous chemotherapy vs chemotherapy-free interval after first line induction. Studies with maintenance fluoropyrimidine and/or bevacizumab were excluded. Primary endpoint was median progression free survival (PFS) and secondary endpoint was median overall survival (OS). z statistics were used for comparing subgroups. All statistical tests were two-sided. P values &lt; 0.05 were considered significant. Results: 1366 patients (55% males) were included in the final analysis. Induction treatment was 5-FU or capecitabine-based chemotherapy with either oxaliplatin or irinotecan with or without bevacizumab. After stratifying for induction status, there was no statistically significant difference in median PFS between continuous vs chemotherapy free interval [Median PFS 4.74-month (95% CI 3.87-5.61) vs 3.52 month (95% CI 2.97-4.07), z-test adjusted p value 0.1383]. No significant difference in median OS between both groups [Median OS 16.95-month (95% CI 15.40-18.50) vs 18.35 month (95% CI 15.17-21.54)]. Conclusions: In mCRC patients, the superiority of continuous chemotherapy was not demonstrated. Further studies should shed light on patient and tumor characteristics most likely to benefit from continuous chemotherapy to limit delivery of cytotoxic therapy to this subset of patients.

A review of capecitabine-based adjuvant therapy for gastric cancer in the Chinese population.

In China, the treatment of locally advanced gastric cancer (AGC) faces unique challenges. Chinese patients may harbor more unfavorable prognostic factors than western populations and, in comparison with other Asian populations such as Japan and South Korea, a higher proportion of Chinese patients are diagnosed with AGC due to inadequate early diagnosis of the malignancy. This review summarizes the use of combination chemotherapy regimens with capecitabine as adjuvant therapy in the Chinese AGC population. Based on the available domestic data in China, the review concludes that capecitabine-based chemotherapy regimens, especially XELOX, offer good efficacy following radical gastrectomy in patients with AGC, with a low incidence of adverse events, acceptable tolerance, greater patient convenience and a lower overall cost than other regimens.

The SNPs in pre-miRNA are related to the response of capecitabine-based therapy in advanced colon cancer patients.

The single nucleotide polymorphisms (SNPs) in the microRNA precursor (pre-miRNA) may modulate the posttranscriptional regulation of gene expression and explain individual sensitivity to chemotherapy. Here we investigated the correlation between 23 SNPs in the pre-miRNA and the efficacy of capecitabine-based chemotherapy in 274 advanced colon cancer patients. Statistical analysis indicated that much more patients with rs744591 A/C(48.03%), C/C (53.45%) or C allele (49.73%) responded to the chemotherapy than those with the A/A genotype (33.71%). The response rates of rs745666 G/C heterozygous patients (35.25%) and C allele carriers (39.69%) were apparently less than that of the G/G homozygous patients (56.25%). Moreover, three SNPs rs2114358, rs35770269, and rs73239138 were significantly associated with the occurrence of side effects of chemotherapy. The patients with rs2114358 C allele (OR = 2.016) or rs35770269 T allele (OR = 2.299) were much more prone to endure adverse events. However, the incidence of side effect was lower in the patients carrying rs73239138 A allele than those with G/G genotype (OR = 0.500). Our findings demonstrate that genetic variations in pre-miRNA may influence the efficacy of capecitabine-based chemotherapy in advanced colon cancer patients.

A polymorphism in ABCC4 is related to efficacy of 5-FU/capecitabine-based chemotherapy in colorectal cancer patients

To investigate the association of microRNA (miRNA) binding-site polymorphisms in the drug transporter genes with the efficacy of 5-Fluorouracil (5-FU)/capecitabine-based chemotherapy in colorectal cancer (CRC), 6 polymorphisms were determined in 432 CRC patients by using DNA sequencing method. The impacts of the polymorphisms on the miRNA-mediated regulation of gene expression were evaluated by using the methods including quantitative real-time PCR, western blotting, and luciferase reporter assays. The effects of miRNA on the intracellular concentration and cytotoxicity of 5-FU in CRC cells were measured by high performance liquid chromatography conjected tandem mass spectrometry (HPLC-MS/MS) and MTT methods, respectively. Statistical analysis showed that a polymorphism rs3742106 in the 3′-UTR of ATP-binding cassette subfamily C member 4 (ABCC4) gene was significantly associated with the efficacy of 5-FU/capecitabine-based chemotherapy in CRC. The patients with T/T genotype had significantly higher response rate than those with G/G and G/T genotypes. The expression of ABCC4 was inhibited by miR-3190-5p through binding to the 3′-UTR of the ABCC4 gene. This regulatory role of miR-3190-5p was disrupted by rs3742106. Furthermore, we found that the intracellular concentration of 5-FU was elevated by miR-3190-5p, and consequently the sensitivity of CRC cells to 5-FU was also enhanced. Rs3742106 might be regarded as a genetic biomarker for individualized use of 5-FU and capecitabine in CRC.

Rs7911488 modified the efficacy of capecitabine-based therapy in colon cancer through altering miR-1307-3p and TYMS expression.

Capecitabine is an orally administered prodrug of 5-fluouracil (5-FU) and is used in first-line treatment of metastatic colorectal cancer. Studies have demonstrated that polymorphisms in 5-FU related ADME genes are associated with the efficacy of capecitabine. However, the relationship between the polymorphisms within the microRNA precursors and the efficacy of capecitabine is still largely unknown. We detected six polymorphisms in 274 colon cancer patients and statistically analyzed the association of the genotypes with the efficacy of capecitabine-based chemotherapy. The mechanisms underlying the effect of genotypes on the efficacy of capecitabine were also studied. We identified a polymorphism rs7911488 T>C in pre-miR-1307 to be significantly associated with the efficacy of capecitabine chemotherapy in colon cancer patients. The response rates of capecitabine chemotherapy for the patients with TT, TC, and CC genotypes were 44.35% (55/124), 51.33% (58/113), and 24.32% (9/37), respectively. In the C-allelic patients, miR-1307-3p is down-regulated and TYMS, a direct target of miR-1307-3p, is over-expressed, which leads to insensitivity of cancer cells to capecitabine chemotherapy. The cancer cells with rs7911488 C allele were further observed to be resistant to 5-FU treatment in vitro and in vivo. Our findings show that rs7911488 C-allelic pre-miR-1307 leads to attenuated miR-1307-3p and elevated TYMS, thus insensitive to capecitabine chemotherapy in colon cancer.

Comparative analysis of the effect of bevacizumab maintenance regimens after first-line chemotherapy in patients with metastatic colorectal cancer (MCRC): A single institution experience.

e15032 Background: The majority of patients with metastatic colorectal cancer (MCRC) will ultimately experience disease progression following initial therapy. Although phase III clinical trials show that continued maintenance therapy improves progression free and overall survival in MCRC, the optimal maintenance regimen with an acceptable safety profile is still undetermined. This study aimed to assess outcomes of bevacizumab-containing maintenance therapy after first line chemotherapy for MCRC. Methods: One hundred thirteen patients (46 males, 67 females) with MCRC diagnosed between 2005 and 2014 who received chemotherapy at Karmanos Cancer Institute were included in this retrospective analysis. Induction treatment for most patients consisted of either 5-FU or capecitabine-based chemotherapy with either oxaliplatin or irinotecan and with or without bevacizumab. Eighty percent of patients who received bevacizumab with induction also received it as part of maintenance therapy. Results: After stratifying for age (dichotomized at 65 years) and induction therapy bevacizumab, there was no difference in PFS for induction regimens with or without bevacizumab (p = 0.67). For patients who received capecitabine as maintenance chemotherapy, the addition of bevacizumab resulted in non-significant larger hazard of a PFS event (HR = 1.46, p = 0.36). Among those who received 5-FU maintenance, the addition of bevacizumab resulted in non-significant smaller hazard of a PFS event (HR = 0.48, p = 0.11). There was no difference in observed toxicities between patients who received bevacizumab and those who did not (p = 0.38), with further sub-set analysis showing no increased toxicities among those who received 5-FU (p = 0.76) and those who received capecitabine (p = 0.16). Conclusions: In patients with metastatic colorectal cancer, there was no difference in efficacy or safety when adding bevacizumab to either 5-FU or capecitabine for maintenance after first line chemotherapy. Based on our results, tolerability and compliance with oral capecitabine ought to be a key factor in determining the choice of maintenance in patients with MCRC.

Identification of new SNPs associated with severe toxicity to capecitabine

Predicting individual risk of chemotherapy-induced severe adverse reaction is a critical issue when selecting the best treatment for cancer patients. SNPs have been identified in genes involved in the pharmacodynamics of fluoropyrimidines, and guidelines even recommend genotyping some DPYD variants in order to estimate the risk of toxicity. However, the predictive value of this approach remains insufficient, thus limiting its clinical implementation. The aim of the present study was to identify new genetic variants by selecting a group of tag SNPs in genes associated with the pharmacodynamics of fluoropyrimidines (CDA, DPYD, ENOSF1, CES1, TYMS, SLC22A7, TYMP, and UMPS). For this purpose, 23 selected SNPs were genotyped on an OpenArray™ platform in a cohort of 301 colorectal cancer patients receiving capecitabine-based chemotherapy. Univariate and multivariate statistical analysis by logistic regression revealed 10 SNPs associated with severe adverse reactions to capecitabine (P<0.05): rs1048977, rs12726436, and rs2072671 in CDA; rs12119882 in DPYD; rs2853741 in TYMS; rs699517 in TYMS/ENOSF1; rs2270860 and rs4149178 in SLC22A7; and rs2279199 and rs4678145 in UMPS. Except for rs2072671, no association had previously been reported between these SNPs and the risk of capecitabine-induced toxicity. The use of tag SNPs to find new polymorphisms related to adverse reactions to capecitabine was successful. These new variants could increase the predictive power of currently available tests and thus prevent severe adverse reactions to capecitabine.

Cardiotoxicity in Chinese cancer patients treated with 5-fluorouracil or capecitabine: A multicenter prospective observational study.

553 Background: Although the cardiotoxicity associated with 5-Fluorouracil (5-FU) or capecitabine administration has been well addressed in literature, there is still a lack of data from prospective clinical trials in Chinese population. The aim of this study was to evaluate the incidence, manifestations and predisposing factors for the cardiotoxicity in Chinese cancer patients treated 5-FU or capecitabine. Methods: A multicenter prospective observational study was performed in 527 patients with various solid tumors from 12 cancer centers in china . Of these patients, 196 received 5-FU-based and 331 received oral capecitabine-based chemotherapy as either first-line or adjuvant therapy. Outcome measures including electrocardiogram(ECG), myocardial enzymes, cardiac troponin(cTn), BNP and echocardio- graphy(UCG) etc. Univariate analysis and the logistic regression were performed for subgroup analysis and identification of the significant independent variables that are associated with cardiotoxicity of both agents. Results: In total, 161 of 527 patients (30.55%) experienced cardiotoxicity. The incidence of cardiotoxicity was 33.84% (112 out of 331) in the capecitabine-treated population, significantly higher than 25 %( 49 out of 196) in the 5-FU treated population (P = 0.0042). 110 out of 527 patients (20.87%) suffered arrhythmia, 105/527 (19.92%) developed ischemic changes, while 20/527(3.80%) heart failure and 6/527 (1.14%) myocardial infarction only. Among the factors evaluated with univariate analysis and the logistic regression, a history of cardiac disease, chemotherapy agent, duration of treatment and hypertension were significant with cardiotoxicity occurrence. The odds ratio were 15.447(with a history of cardiac history vs without), 2.118 (Capecitabine group vs 5-FU group), 1.079(5-8 vs 1-4 cycles) and 1.698 (with hypertension vs without) respectively. Conclusions: Cardiotoxicity induced by fluoropyrimidines in Chinese population may be underestimated in clinical practice.Possible risk factors are duration of treatment, chemotherapy agents, preexisting cardiac disease and hypertension.

Role of pelvic radiotherapy for locally advanced rectal cancer and synchronous unresectable distant metastases

PurposeTo evaluate the efficacy and safety of pelvic irradiation combined systematic chemotherapy in patients with locally advanced (cT3–T4 and/or cN+) rectal cancer and synchronous unresectable distant metastases. Patients and methodsA total of 76 eligible patients who received pelvic radiotherapy and concurrent capecitabine-based chemotherapy were retrospectively reviewed. Patients survival curves were constructed using the Kaplan-Meier method, and a multivariate analysis was performed to identify independent prognostic factors. ResultsMost of the adverse events were mild during the period of combined chemoradiotherapy. Twenty-two patients experienced resection of primary tumour and 16 patients underwent radical surgery of all lesions. Only five patients had pelvic progression during the follow-up period. The median progression-free survival and median overall survival were 13 and 30 months, respectively. Radical surgery of all lesions following chemoradiotherapy was found to be an independent prognostic factor according to multivariate analysis. ConclusionsPelvic irradiation combined with systematic chemotherapy in patients with locally advanced rectal cancer and synchronous unresectable distant metastases is effective and tolerable, both for pelvic and distant control. A curative resection following chemoradiotherapy was associated with prolonged survival.

Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis.

BackgroundColorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). MethodsSeveral databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI).ResultsThe final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003).ConclusionThe combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher in those subgroups of patients receiving bolus 5-FU or capecitabine-based chemotherapy plus bevacizumab, when compared to patients treated with infusional %-FU plus bevacizumab (no difference in PFS and OS). Regarding the type of cytotoxic scheme, regimens containing irinotecan and fluoropyrimidine monotherapy showed superior efficacy results when combined to bevacizumab.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2734-y) contains supplementary material, which is available to authorized users.

A pilot study of neoadjuvant chemoradiotherapy for unresectable locally advanced adherent colon cancer: Assessing local tumor response.

727 Background: To analyze the outcomes of neoadjuvant chemoradiotherapy (neoCRT) in the management of unresectable locally advanced adherent colon cancer (LAACC). Methods: 40 unresectable LAACC patients were identified from Sun Yat-Sen university cancer-center Database from October 2010 to December 2014. Unresectability was determined by multidisciplinary consultation (MDT) according to image examination or confirmed by exploratory laparotomy. NeoCRT followed by surgery and postoperative chemotherapy were given to these patients. There were 27 males and 13 females. Median age was 56 years old. The location of primary tumors were as sigmoid 31, descending colon 3, ascending colon 5, and cecum1, respectively. All the patients were treated with 45-50Gy/25F using 3D-CRT or IMRT, and concomitantly with capecitabine-based chemotherapy every 3 weeks. Surgery was scheduled 6-8 weeks after completion of radiotherapy. Results: A total of 40 patients completed neoCRT and 33 patients (82.5%) received radical resection for the locally diseases, with R0 and R2 resection in 30 and 3 patients, respectively. Seven patients were assessed as unresectable after neoCRT and 3 of them received only colostomy while the other 4 continued chemotherapy. Pathological complete response was documented in 8 patients (20.0%). Multivisceral resection was necessary in 15 patients (36.6%). Among the 33 patients underwent curative surgery, bladder invasion was noticed at diagnosis in 17 patient and bladder function was preserved in all these patients, with full bladder preserving approach in 6 and partial cystectomy in 11 patients. Grade-2 post-operative complications were observed in 4 patients (10.0%) with no 30-day mortality. Median follow-up was 26 months. For all the patients, the 3-year overall survival, local progression-free survival and progression-free survival were 70.8%, 88.2%, 74.5%, respectively. Conclusions: NeoCRT is an effective strategy for the treatment of unresectable LAACC, with high R0 resection rate, satisfactory organ preservation, good local control and acceptable treatment toxicity. NeoCRT in LAACC is worthy of further clinical research.

Self-identification and management of hand-foot syndrome (HFS): effect of a structured teaching program on patients receiving capecitabine-based chemotherapy for colon cancer.

Capecitabine is an oral prodrug of 5-fluorouracil and is commonly used oral chemotherapeutic drugs for advanced gastric and colorectal cancer. However, hand-foot syndrome (HFS) has high incidence, and once developed, the symptoms significantly impair quality of life (QOL), leading to a reduction in the dosage or discontinuation of the treatment. Effective health education should be offered to patients to promote self-identification and management on how to recognize HFS and use self-management techniques at the very beginning of chemotherapy. The present study intended to evaluate the effectiveness of structured teaching program on knowledge related to self-identification and management of HFS among patients receiving chemotherapy for colon cancer at tertiary cancer care center. Participants who fulfilled the criteria were selected using non-probability purposive sampling. The sample selected were 40 participants (20 participants in experimental group and 20 participants in control group). Among the group of 40 patients, 17 (85%) participants in the experimental group and 17 (85%) participants in the control group were receiving capecitabine and oxaliplatin (CAPOX) chemotherapy treatment protocol. Five (25%) participants in the experimental group and ten (50%) participants in the control group were receiving drug capecitabine at a dose of 2500mg. The mean knowledge (knowledge related to self-identification and management of HFS) pretest score was 6.75 and mean knowledge posttest score was 10.25 in the experimental group which was statistically significant (p = 0.000) (p < 0.05). The mean knowledge pretest score of participants was 6.45 and mean knowledge posttest score of participants was 6.75 in the control group which was not statistically significant (p = 0.67) (p > 0.05). The study showed a statistically significant improvement in knowledge scores of participants that occurred due to intervention of structured teaching program. This can be used to assess reduction in incidence of HFS in the future.

Efficacy and safety of capecitabine-based first-line chemotherapy in advanced or metastatic breast cancer: a meta-analysis of randomised controlled trials.

We sought to evaluate the efficacy and safety of capecitabine-based therapy as first-line chemotherapy in advanced breast cancer. Randomised controlled trials of capecitabine monotherapy or combined treatment were included in the meta-analysis. PubMed, EMBASE, the Cochrane Library database and important meeting summaries were searched systematically. Outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and grades 3-4 drug-related adverse events.Nine trials with 1798 patients were included. The results indicated a significant improvement with capecitabine-based chemotherapy compared with capecitabine-free chemotherapy in ORR (relative risk [RR] 1.14, 95% confidence interval [CI] 1.03 to 1.26, P = 0.013) and PFS (hazard ratio [HR] 0.77, 95% CI 0.69 to 0.87, P < 0.0001). Overall survival favoured capecitabine-based chemotherapy, but this was not significant. There were more incidences of neutropenia and neutropenic fever in the capecitabine-free chemotherapy group and more vomiting, diarrhoea and hand-foot syndrome in the capecitabine-based chemotherapy group. There were no significant differences in nausea, fatigue, cardiotoxicity or mucositis/stomatitis between the two treatment regimens.Capecitabine-based chemotherapy significantly improves ORR and PFS in patients with advanced breast cancer, but has no demonstrable impact on OS. Capecitabine-based regimens are suitable as first-line treatment for patients with advanced breast cancer.

Clinical observation of external compound Chinese herbal extract LC09 with capecitabine maintenance therapy after response to capecitabine-based combination chemotherapy in patients with metastatic breast cancer.

e12006 Background: Capecitabine(Cape) maintenance therapy after response to Cape-based combination chemotherapy(chemo) is one of the standard regimens recommended by NCCN for metastatic breast canc...