Capecitabine Plus Oxaliplatin Plus Bevacizumab as First-line Treatment in Elderly Patients With Metastatic Colorectal Cancer
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ABSTRACT:
DISEASE(S): Metastatic Colorectal Cancer,Colorectal Cancer,Colorectal Neoplasms,Cancer
PROVIDER: 2081614 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:BackgroundSubgroup analyses of clinical studies suggest that bevacizumab plus XELOX is effective and tolerable in elderly patients with metastatic colorectal cancer (mCRC). The prospective BECOX study examined the efficacy and safety of bevacizumab plus XELOX, followed by bevacizumab plus capecitabine in elderly patients with mCRC.MethodsPatients aged ⩾70 years with Eastern Cooperative Oncology Group performance status 0 out of 1 and confirmed mCRC were included. Patients received bevacizumab 7.5 mg kg(-1) and oxaliplatin 130 mg m(-2) on day 1, plus capecitabine 1000 mg m(-2) bid orally on days 1-14 every 21 days; oxaliplatin was discontinued after 6 cycles. The primary end point was time to progression (TTP).ResultsThe intent-to-treat population comprised 68 patients (65% male, median age 76 years). Median TTP was 11.1 months; median overall survival was 20.4 months; overall response rate was 46%. Grade 3 or 4 adverse events included diarrhoea (18%) and asthenia (16%). Grade 3 or 4 adverse events of special interest for bevacizumab included deep-vein thrombosis (6%) and pulmonary embolism (4%).ConclusionsBevacizumab plus XELOX was effective and well tolerated in elderly patients in the BECOX study. The adverse-event profile was similar to previous reports; no new safety concerns were identified. Fit elderly patients with mCRC should be considered for treatment with bevacizumab plus XELOX.
| S-EPMC4102952 | biostudies-literature
Project description:Background: In the first-line treatment of biliary tract cancers (BTCs), XELOX (capecitabine plus oxaliplatin) showed comparable clinical efficacy and safety to gemcitabine and oxaliplatin (GEMOX), with fewer visits and better treatment management. Our study aims to investigate the cost-effectiveness of XELOX and GEMOX as the first-line therapy for BTCs from the perspective of the Chinese healthcare systems and to provide valuable suggestions for clinical decision-making. Methods: A Markov model was developed using the phase 3 randomized clinical trial (ClinicalTrials.gov number, NCT01470443) to evaluate the cost-effectiveness of XELOX and GEMOX. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were used as the primary outcomes of the model. Uncertainty was assessed using univariate and probabilistic sensitivity analysis. Results: The QALYs for the XELOX and GEMOX groups were 0.66 and 0.54, respectively. In China, the total cost of XELOX treatment is US $12,275.51, which is lower than that of the GEMOX regimen. In addition, XELOX is more effective than GEMOX, making it the preferred regimen. A sensitivity analysis determined that XELOX therapy has a stable economic advantage in China. Conclusion: Compared to GEMOX, XELOX is a more cost-effective treatment as a first-line treatment for advanced BTC from the perspective of the Chinese health service system.
| S-EPMC9354395 | biostudies-literature
Project description:* Oxaliplatin-based doublets plus bevacizumab are standard first-line therapy options for patients (pts) with metastatic colorectal cancer (mCRC). Slight adjustments in chemo-dosage are commonly applied in routinely practice to elderly pts, but those modified schedules have never been standardized
* The addition of oxaliplatin versus no oxaliplatin to treatment with 5-fluorouracil in older and frail untreated pts with mCRC resulted in a non-statistically significant trend toward improvement in Progression Free Survival (PFS) and a lack of benefit in Overall Survival (OS)
* In elderly pts deemed unfit for an upfront combined chemotherapy a fluoropyrimide-based monotherapy plus bevacizumab is considered a reasonable first-line treatment
* Clinical definition of elderly (over 70 years old) pts with CRC that may deserve a more or less intensive combination therapy is still debated. The cut-off of 75 years old combined with ECOG PS assessment is a reasonable approach for clearly defining candidates to different approaches
* Several geriatric screening tools have been used to identify pts with a geriatric profile potentially predicting for overall survival and risk of toxicity. The G8 screening tool has been already validated in pts with cancer showing the strongest prognostic value for OS; the CRASH score is able to stratify pts according an estimated risk of treatment-related toxicities
On the basis of these considerations, we designed the present observational study of first-line therapy with bevacizumab in combination with capecitabine and oxaliplatin in previously untreated elderly pts affected by unresectable mCRC in order to evaluate its efficacy in real world practice (as measured by progression free survival)
| 2267266 | ecrin-mdr-crc
Project description:BACKGROUND: The efficacy and safety of capecitabine and bevacizumab in elderly patients with metastatic colorectal cancer (mCRC) considered unsuitable for receiving first-line chemotherapy with an irinotecan or oxaliplatin-based combination were assessed in a phase II, open, multicentre, uncontrolled study. METHODS: Treatment consisted of capecitabine 1250 mg m(-2) (or 950 mg m(-2) for patients with a creatinine clearance of 30-50 ml min(-1)) twice daily on days 1-14 and bevacizumab (7.5 mg kg(-1)) on day 1 every 3 weeks. RESULTS: A total of 59 patients aged >or=70 years with mCRC were enrolled. In an intention-to-treat analysis, the overall response rate was 34%, with 71% of patients achieving disease control. Median progression-free survival and overall survival were 10.8 months and 18 months, respectively. In all, 32 patients (54%) had grade 3/4 adverse events (AEs), the most common being hand-foot syndrome (19%), diarrhoea (9%) and deep venous thrombosis (7%). Four patients died because of treatment-related AEs. A relationship was detected between creatinine clearance <or=50 ml min(-1) and the development of non-bevacizumab-related grade 3/4 AEs. The incidence of bevacizumab-associated AEs (hypertension, thromboembolic events and proteinuria) was consistent with that of previous reports in elderly patients. CONCLUSION: Bevacizumab combined with capecitabine represents a valid therapeutic alternative in elderly patients considered to be unsuitable for receiving polychemotherapy.
| S-EPMC2869164 | biostudies-other
Project description:BackgroundA targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy.Patients and methodsPatients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety.ResultsThree hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75-1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81-1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups.ConclusionBevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment.Clinical trial identifierUMIN000002557.
| S-EPMC4478977 | biostudies-literature
Project description:We report updated progression-free survival (PFS) and overall survival (OS) data from a trial that compared capecitabine plus oxaliplatin (CapeOX) versus S-1 plus oxaliplatin (SOX) for the first-line treatment of metastatic colorectal cancer.This trial was a randomized, two-armed, non-inferiority phase 3 comparison of CapeOX (capecitabine 1000 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1) versus SOX (S-1 40 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1). The primary end point was to show non-inferiority of SOX relative to CapeOX in terms of PFS. Thus, a follow-up exploratory analysis of PFS and OS was performed.The intention to treat (ITT) population was comprised of 340 patients (SOX arm: 168 and CapeOX arm: 172). The updated median PFS was 7.1 months (95% CI 6.4-8.0) in the SOX group and 6.3 months (95% CI 4.9-6.7) in the CapeOX group (hazard ratio [HR], 0.83 [0.66-1.04], p =?.10). The median OS was 19.0 months (95% CI 15.3-23.0) in the SOX group and 18.4 months (95% CI 14.1-20.7) in the CapeOX group (HR, 0.86 [0.68-1.08], p =?.19). Subgroup analyses according to principal demographic factors such as sex, age, ECOG (Eastern Cooperative Oncology Group) performance status, primary tumor location, measurability, previous adjuvant therapy, number of metastatic organs, and liver metastases showed no interaction between any of these characteristics and the treatment.Updated survival analysis shows that SOX is similar to CapeOX, confirming the initial PFS analysis. Therefore, the SOX regimen could be an alternative first-line doublet chemotherapy strategy for patients with metastatic colorectal cancer.NCT00677443 and May 12 2008.
| S-EPMC4289339 | biostudies-literature
Project description:Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question whether this statement holds true also for bevacizumab-based first-line treatment including escalation- and de-escalation strategies.The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m(2) bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m(2) BID for 14d (d1-14), irinotecan 200 mg/m(2) (d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumour tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are overall response rate (ORR), overall survival, progression-free survival, safety and quality of life.The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary.ClinicalTrials.gov Identifier NCT01249638 EudraCT-No.: 2009-013099-38.
| S-EPMC3173448 | biostudies-literature
Project description:BackgroundMicrosatellite stable (MSS) and RAS-mutant metastatic colorectal cancer (mCRC) patients are characterized by an immunosuppressive microenvironment and a low response rate to immunotherapy. Chemotherapy and anti-angiogenesis therapy have been reported to potentially promote immunotherapy response. This study aims to assess the preliminary anti-tumor activity and safety of sintilimab plus bevacizumab, oxaliplatin and capecitabine as a treatment option for patients with RAS-mutant MSS mCRC.MethodsThis study was an open-label, single-arm, phase II trial in China. Patients with unresectable, RAS-mutant and MSS metastatic colorectal adenocarcinoma received treatment by intravenous sintilimab (200 mg, day 1) plus bevacizumab (7.5 mg/kg, day 1), oxaliplatin (135 mg/m2, day 1) and oral capecitabine (1 g/m2, day 1-14) in each 21-day cycle. The primary endpoints included objective response rate (ORR) and adverse events. Biomarker analysis was performed to identify potential predictors of good response to treatment. This study is registered with ClinicalTrials.gov, number NCT04194359.FindingsBetween April 2021 and December 2021, 25 patients were enrolled. Two (8%) patients showed complete response (CR), 19 (76%) had partial response (PR) and 4 (16%) presented with stable disease. ORR reached 84% (95% CI, 63.9-95.5) and the disease control rate was 100% (95% CI, 86.3-100). The median progression-free survival (PFS) was 18.2 months for the full analysis set. The most common treatment-related adverse events (TRAEs) in all grades were anemia (21/25, 84%), neutropenia (20/25, 80%), and hand-foot syndrome (14/25, 56%). The most frequent grade 3 or 4 TRAEs were neutropenia (3/25, 12%) and increased alanine transaminase (2/25, 8%). No grade 5 adverse events occurred. In the exploration of biomarkers, 5 patients could be characterized as TTN/OBSCN "double-hit" after treatment, and the copy number variants burden was significantly decreased in tumor tissues after treatment compared with the baseline. Nanostring panel RNA sequencing analysis indicated a better tumor immune microenvironment cell infiltration in CR/PR patients compared with non-CR/PR patients as well as the PFS-long (≥12.5 months) group compared with the PFS-short group.InterpretationCombination treatment with sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line treatment demonstrated a promising antitumor activity and a manageable safety profile in RAS-mutant, MSS and unresectable mCRC. Exploratory biomarker assessment analysis showed that some RAS-mutant and MSS patients changed into "immune-hot" subtype after the treatment.FundingThis study was supported by the Key R&D Program of Zhejiang Province (2021C03125 to Ying Yuan), the National Natural Science Foundation of China (81872481 to Ying Yuan, 82072624 to Kefeng Ding), the Fundamental Research Funds for the Central Universities (No. 226-2022-00009 to Kefeng Ding), and the Zhejiang Provincial Natural Science Foundation of China (No. LY22H160024 to Hanguang Hu).
| S-EPMC10404864 | biostudies-literature
Project description:BackgroundThere is no single standard chemotherapy regimen for elderly patients with advanced gastric cancer (AGC). A phase III trial has confirmed that both capecitabine monotherapy and capecitabine plus oxaliplatin are well tolerated for elderly patients with AGC, but their economic influence in China is unknown.ObjectiveThe purpose of this cost-effectiveness analysis was to estimate the effects of capecitabine monotherapy and capecitabine plus oxaliplatin in elderly patients with AGC on health and economic outcomes in China.MethodsWe created a Markov model based on data from a Korean clinical phase III trial to analyze the cost-effectiveness of the treatment of elderly patients in the capecitabine monotherapy (X) group and capecitabine plus oxaliplatin (XELOX) group. The costs were obtained from published reports and the local health system. The utilities were assumed on the basis of the published literature. Costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER) were estimated. One-way and probabilistic sensitivity analyses (Monte Carlo simulations) were performed.ResultsIn the cost-effectiveness analysis, X had a lower total cost ($45,731.68) and cost-effectiveness ratio ($65,918.93/QALY). The one-way sensitivity analysis suggested that the most influential parameter was the risk of requiring second-line chemotherapy in XELOX group. The probabilistic sensitivity analysis predicted that the X regimen was cost-effective 100% of the time, given a willingness-to-pay threshold of $26,598.ConclusionsOur findings show that the XELOX regimen is less cost-effective compared to the X regimen for elderly patients with AGC in China from a Chinese healthcare perspective.
| S-EPMC6023138 | biostudies-literature
Project description:There is substantial germline genetic variability within angiogenesis pathway genes, thereby causing interindividual differences in angiogenic capacity and resistance to antiangiogenesis therapy. We investigated germline polymorphisms in genes involved in VEGF-dependent and -independent angiogenesis pathways to predict clinical outcome and tumor response in metastatic colorectal cancer (mCRC) patients treated with bevacizumab and oxaliplatin-based chemotherapy.A total of 132 patients treated with first-line bevacizumab and FOLFOX or XELOX were included in this study. Genomic DNA was isolated from whole-blood samples by PCR-RFLP or direct DNA sequencing. The endpoints of the study were progression-free survival (PFS), overall survival (OS), and response rate (RR).The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were associated with increased OS and remained significant in multivariate Cox regression analysis (HR: 0.52; 95% CI: 0.31-0.87; adjusted P = 0.012 and HR: 0.60; 95% CI: 0.36-0.99; adjusted P = 0.046, respectively). The minor allele of HIF1? rs11549465 C>T was significantly associated with increased PFS but lost its significance in multivariate analysis. CXCR1 rs2234671 G>C, CXCR2 rs2230054 T>C, EGFR rs2227983 G>A, and VEGFR-2 rs2305948 C>T predicted tumor response, with CXCR1 rs2234671 G>C remaining significant in multiple testing (P(act) = 0.003).In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy.
| S-EPMC3174848 | biostudies-literature