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1.
Cassidy J Clarke S Díaz-Rubio E Scheithauer W Figer A Wong R Koski S Rittweger K Gilberg F Saltz L 《British journal of cancer》2011,105(1):58-64
Background:
We report updated overall survival (OS) data from study NO16966, which compared capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX4) as first-line therapy in metastatic colorectal cancer.Methods:
NO16966 was a randomised, two-arm, non-inferiority, phase III comparison of XELOX vs FOLFOX4, which was subsequently amended to a 2 × 2 factorial design with further randomisation to bevacizumab or placebo. A planned follow-up exploratory analysis of OS was performed.Results:
The intent-to-treat (ITT) population comprised 2034 patients (two-arm portion, n=634; 2 × 2 factorial portion, n=1400). For the whole NO16966 study population, median OS was 19.8 months in the pooled XELOX/XELOX-placebo/XELOX-bevacizumab arms vs 19.5 months in the pooled FOLFOX4/FOLFOX4-placebo/FOLFOX4-bevacizumab arms (hazard ratio 0.95 (97.5% CI 0.85–1.06)). In the pooled XELOX/XELOX-placebo arms, median OS was 19.0 vs 18.9 months in the pooled FOLFOX4/FOLFOX4-placebo arms (hazard ratio 0.95 (97.5% CI 0.83–1.09)). FOLFOX4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhoea and grade 3 hand-foot syndrome than FOLFOX4.Conclusion:
Updated survival data from study NO16966 show that XELOX is similar to FOLFOX4, confirming the primary analysis of progression-free survival. XELOX can be considered as a routine first-line treatment option for patients with metastatic colorectal cancer. 相似文献2.
J Feliu A Salud M J Safont C García-Girón J Aparicio R Vera O Serra E Casado M Jorge P Escudero C Bosch U Bohn R Pérez-Carrión A Carmona V Martínez-Marín J Maurel 《British journal of cancer》2014,111(2):241-248
Background:
Subgroup 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.Methods:
Patients 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).Results:
The 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%).Conclusions:
Bevacizumab 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. 相似文献3.
Background.
Capecitabine administered for 7 days biweekly with oxaliplatin (XELOX) biweekly has been reported to have activity and safety profiles similar to those of standard capecitabine given for 14 days triweekly. Multiple studies have shown that the addition of bevacizumab to 5-fluorouracil–based chemotherapy is active and well tolerated.Methods.
Patients with metastatic colorectal cancer (mCRC) were randomized to XELOX plus bevacizumab using a standard triweekly cycle (Q3W) or a dose-dense biweekly cycle (Q2W) schedule. The primary endpoint was the progression-free survival (PFS) interval. This trial is registered on ClinicalTrials.gov (identifier, NCT00159432).Results.
In total, 435 U.S. patients were randomized. The median PFS intervals were 9.6 months in the Q3W group and 9.1 months in the Q2W group. The median overall survival times were 28.4 months and 22.1 months and the median times to treatment failure were 5.5 months and 3.4 months, respectively. Overall, gastrointestinal disorders were the most common (93%) adverse event (AE). Grade 3 or 4 AEs occurred in 75% and 81% of patients in the Q3W and Q2W groups, respectively. Treatment discontinuation as a result of diarrhea (5% versus 10%) and hand–foot syndrome (2% versus 9%) was less common in the Q3W group than in the Q2W group, respectively.Conclusions.
Based on these results, the first-line treatment of U.S. patients with mCRC using a biweekly combination of XELOX and bevacizumab at the doses studied cannot be recommended. XELOX Q3W remains the preferred schedule for the management of mCRC. 相似文献4.
T Hoehler G von Wichert C Schimanski S Kanzler M H Moehler A Hinke T Seufferlein J Siebler A Hochhaus D Arnold M Hallek R Hofheinz U T Hacker 《British journal of cancer》2013,109(6):1408-1413
Background:
Combined inhibition of platelet-derived growth factor receptor beta signalling and vascular endothelial growth factor promotes vascular normalisation in preclinical models and may lead to increased delivery of chemotherapy to tumour tissue. This phase I/II trial assessed the safety and efficacy of capecitabine plus oxaliplatin (XELOX) plus bevacizumab and imatinib in the first-line treatment of patients with metastatic colorectal cancer.Methods:
Two dose levels (I/II) were defined: capecitabine 850/1000 mg m−2 twice daily on days 1–14; oxaliplatin 100/130 mg m−2 on day 1; bevacizumab 7.5 mg kg−1 on day 1; imatinib 300 mg day−1 on days 1–21 every 21 days. The primary study endpoint was safety. The phase II secondary endpoint was 6-month progression-free survival (PFS).Results:
Dose level I was chosen for phase II testing because, even though further dose escalation was permitted by the protocol, gastrointestinal toxicities were considered to be clinically significant. A total of 49 patients were evaluated. The 6-month PFS rate was 76%, median PFS was 10.6 months and median overall survival was 23.2 months. Haematological toxicities were generally mild. Sensory neuropathy and diarrhoea were the most common grade 3 toxicities.Conclusion:
The combination of XELOX with bevacizumab and imatinib is tolerable and has promising efficacy. 相似文献5.
Hope E. Uronis Johanna C. Bendell Ivy Altomare Gerard C. Blobe S. David Hsu Michael A. Morse Herbert Pang S. Yousuf Zafar Paul Conkling Justin Favaro Christy C. Arrowood Stephanie M. Cushman Kellen L. Meadows John C. Brady Andrew B. Nixon Herbert I. Hurwitz 《The oncologist》2013,18(3):271-272
Background.
Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. We evaluated the safety, tolerability, and efficacy of the combination capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas.Methods.
Thirty-seven patients with metastatic or unresectable gastric/gastroesophageal junction tumors were enrolled and treated with capecitabine 850 mg/m2 BID on days 1–14, and oxaliplatin 130 mg/m2 with bevacizumab 15 mg/kg on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Neuropilin-1 (NRP1) and -2 (NRP2) mRNA expression was evaluated in archived tumor.Results.
Thirty-five patients were evaluable for efficacy. Median PFS was 7.2 months; median OS was 10.8 months. RR was estimated at 51.4%. The regimen was tolerable with expected drug class-related toxicities. NRP2 mRNA levels significantly correlated with PFS (p = 0.042) and showed a trend toward significance with OS (p = 0.051). Nonsignificant trends for NRP1 were noted for higher expression levels and worse outcome.Conclusions.
Bevacizumab can be given safely with chemotherapy in patients with metastatic esophagogastric adenocarcinomas. The combination of capecitabine, oxaliplatin, plus bevacizumab has activity comparable to other bevacizumab-containing regimens in metastatic gastroesophageal cancer. 相似文献6.
T. Waddell S. Gollins W. Soe J. Valle J. Allen D. Bentley J. Morris A. Lloyd R. Swindell M. B. Taylor M. P. Saunders 《Cancer chemotherapy and pharmacology》2011,67(5):1111-1117
Purpose
To evaluate the efficacy, safety and quality of life of a short course of oxaliplatin plus capecitabine (XELOX) followed by single-agent capecitabine in patients with previously untreated, inoperable, metastatic colorectal cancer.Methods
Patients received intravenous oxaliplatin 130?mg/m2 on d1 plus oral capecitabine 1,000?mg/m2 twice daily (bid) on d1?C14 every 21?days for four cycles. Patients achieving stable disease (SD) or better than received capecitabine 1,250?mg/m2 bid on d1?C14 every 21?days until disease progression. The primary endpoint was progression-free survival (PFS).Results
Overall, 21/45 (47%) of patients responded to the initial XELOX chemotherapy whilst SD or better was documented in 76%. Median PFS was 6.7 (95% CI 5.7?C9.6) months, and median overall survival (OS) was 20.5 (95% CI 13.1?C28.1) months. In the 34 patients who then received capecitabine maintenance therapy, the median PFS was 8.1 (95% CI 6.2?C11.8) months and median OS was 23.1 (95% CI 17.8?C28.5) months. A marked reduction in the vast majority of all grades of adverse event occurred on switching from initial XELOX to maintenance capecitabine chemotherapy including grades 1?C2 (77 vs. 47%) and grade 3 (7 vs. 3%) neuropathy, diarrhoea and lethargy.Conclusions
Short-course XELOX followed by capecitabine maintenance therapy provides an active and well-tolerated treatment option for patients with previously untreated metastatic colorectal cancer. A median OS of more than 20?months is promising and by limiting the number of oxaliplatin infusions, this approach minimises the risk of unwanted cumulative neurotoxicity, is cheaper and more convenient for both patients and healthcare providers. 相似文献7.
Takeru Shiroiwa Takashi Fukuda Kiichiro Tsutani 《International journal of clinical oncology / Japan Society of Clinical Oncology》2010,15(3):256-262
Objective
The purpose of our study was to estimate the out-of-pocket payment and cost-effectiveness of capecitabine plus oxaliplatin (XELOX) or XELOX plus bevacizumab from the perspective of patients with metastatic colorectal cancer (MCRC).Methods
Based on the NO16966 and NO16967 trials, the mean out-of-pocket payment was calculated from patient-level data. Out-of-pocket payments for 16 cycles (11 months) of first-line chemotherapy and 8 cycles (5 months) of second-line chemotherapy were included. In addition, incremental cost-effectiveness ratios (ICERs) for first-line bevacizumab were calculated by dividing the difference of the out-of-pocket payment by the difference of the mean number of progression-free survival (PFS) years or quality-adjusted PFS (QAPFS) years.Results
The mean out-of-pocket payments for middle-income patients under 70 years of age were JPY 328,000 for 16 cycles of first-line XELOX and JPY 376,000 for XELOX plus bevacizumab. The mean out-of-pocket payment for 8 cycles of second-line XELOX was calculated to be JPY 175,000. Middle-income patients over 70 years of age were required to pay JPY 61,000 and JPY 72,000 for first-line XELOX and XELOX plus bevacizumab, respectively. The ICERs of middle-income patients <70 years of age were JPY 430,000/PFS-year and JPY 720,000/QAPFS-year, and those of middle-income patients >70 years of age were JPY 100,000/PFS-year and JPY 170,000/QAPFS-year.Conclusions
We clarified the out-of-pocket payment and cost-effectiveness of chemotherapy of MCRC patients in Japan. Our previous survey shows it is highly possible that many patients prefer to pay that incremental out-of-pocket payment to gain one additional QAPFS year. However, our cost-effectiveness analysis was not conducted from the perspective of society or healthcare payers. 相似文献8.
Nogué M Salud A Vicente P Arriví A Roca JM Losa F Ponce J Safont MJ Guasch I Moreno I Ruiz A Pericay C;AVACROSS Study Group 《The oncologist》2011,16(5):614-620
Background.
Concomitant chemoradiotherapy followed by total mesorectal excision is standard treatment for locally advanced rectal cancer. This approach, however, focuses on local disease control and delays systemic treatment. Induction chemotherapy has the advantage of earlier administration of systemic therapy and may improve distant control. The objective of the current study was to assess the efficacy and toxicity of adding bevacizumab to induction chemotherapy followed by preoperative bevacizumab-based chemoradiotherapy in patients with locally advanced rectal cancer.Patients and Methods.
Eligible patients had high-risk rectal adenocarcinoma defined by magnetic resonance imaging criteria. Treatment consisted of four 21-day cycles of bevacizumab (7.5 mg/kg) and XELOX (capecitabine plus oxaliplatin), followed by concomitant radiotherapy (50.4 Gy) plus bevacizumab (5 mg/kg every 2 weeks) and capecitabine (825 mg/m2 twice daily on days 1–15). Surgery was scheduled for 6–8 weeks after chemoradiotherapy. The primary endpoint was pathologic complete response (pCR).Results.
Between July 2007 and July 2008, 47 patients were recruited. Among 45 patients who underwent surgery, pCR was achieved in 16 patients (36%; 95% confidence interval: 22.29%–51.27%), and an additional 17 patients (38%) had Dworak tumor regression grade 3. R0 resection was performed in 44 patients (98%). Most grade 3/4 adverse events occurred during the induction phase and included diarrhea (11%), asthenia (4%), neutropenia (6%), and thrombocytopenia (4%). Eleven patients (24%) required surgical reintervention.Conclusions.
Addition of bevacizumab to induction chemotherapy and chemoradiotherapy is feasible, with impressive activity and manageable toxicity. However, caution is recommended regarding surgical complications. 相似文献9.
Johanna C. Bendell Tanios S. Bekaii‐Saab Allen L. Cohn Herbert I. Hurwitz Mark Kozloff Haluk Tezcan Nancy Roach Yong Mun Susan Fish E. Dawn Flick Darshan Dalal Axel Grothey 《The oncologist》2012,17(12):1486-1495
Background.
The Avastin® Registry: Investigation of Effectiveness and Safety (ARIES) study is a prospective, community-based observational cohort study that evaluated the effectiveness and safety of first-line treatment patterns, assessing the impact of chemotherapy choice and treatment duration.Methods.
The ARIES study enrolled patients with metastatic colorectal cancer (mCRC) receiving first-line chemotherapy with bevacizumab and followed them longitudinally. The protocol did not specify treatment regimens or assessments. Analyses included all patients who initiated bevacizumab in combination with either first-line oxaliplatin with infusional 5-fluorouracil and leucovorin (FOLFOX) or irinotecan with infusional 5-fluorouracil and leucovorin (FOLFIRI). Progression-free survival (PFS) and overall survival (OS) times were estimated using Kaplan–Meier methods. Hazard ratios (HRs) were estimated with multivariate Cox regression analysis, adjusting for potential confounding factors.Results.
In total, 1,550 patients with first-line mCRC were enrolled (median follow-up, 21 months) and most received FOLFOX–bevacizumab (n = 968) or FOLFIRI–bevacizumab (n = 243) as first-line therapy. The baseline characteristics and median treatment duration were generally similar between subgroups. There were no significant differences in the median PFS (10.3 months vs. 10.2 months) or OS (23.7 months vs. 25.5 months) time between the FOLFOX–bevacizumab and FOLFIRI–bevacizumab subgroups, respectively, by unadjusted analyses. Multivariate analyses showed FOLFIRI–bevacizumab resulted in a similar PFS (HR, 1.03; 95% confidence interval [CI], 0.88–1.21) and OS (HR, 0.95; 95% CI, 0.78–1.16) outcome as with FOLFOX–bevacizumab. The incidence proportions of bevacizumab-associated adverse events were similar for FOLFOX- and FOLFIRI-based therapies.Conclusions.
In first-line mCRC patients, the FOLFOX–bevacizumab and FOLFIRI–bevacizumab regimens were associated with similar treatment patterns and clinical outcomes. 相似文献10.
J M Jürgensmeier H-J Schmoll J D Robertson L Brooks M Taboada S R Morgan D Wilson P M Hoff 《British journal of cancer》2013,108(6):1316-1323
Background:
The prognostic/predictive value of potential vascular endothelial growth factor (VEGF) signalling biomarkers was evaluated retrospectively using samples from two randomized Phase III studies (HORIZON II and III) investigating cediranib in metastatic colorectal cancer (mCRC).Methods:
Baseline levels of VEGF, soluble VEGF receptor-2 (sVEGFR-2) and carcinoembryonic antigen (CEA) were measured in plasma/serum samples collected from patients participating in HORIZON II (n=860; FOLFOX/XELOX plus cediranib 20 mg (n=502) or placebo (n=358)) and HORIZON III (n=1422; mFOLFOX6 plus cediranib 20 mg (n=709) or bevacizumab (n=713)). Median biomarker baseline levels determined cutoff values for the patient subgroups.Results:
Baseline data were available for 88–97% of patients/study (>2000 patients). In both the studies, high baseline VEGF and CEA were associated with worse outcomes for progression-free survival (PFS) and overall survival (OS) independent of treatment (HORIZON II OS: VEGF, hazard ratio (HR)=1.35 (95% confidence interval (CI): 1.12–1.63); CEA, HR=1.63 (1.36–1.96); HORIZON III OS: VEGF, HR=1.32 (1.12–1.54); CEA, HR=1.50 (1.29–1.76)). sVEGFR-2 was not prognostic for PFS/OS. Baseline VEGF and CEA were not predictive for PFS/OS outcome to cediranib treatment; low sVEGFR-2 was associated with a trend towards improved cediranib effect in HORIZON II.Conclusion:
Baseline VEGF and CEA levels were treatment-independent prognostic biomarkers for PFS and OS in both the studies. 相似文献11.
C-H Hsu T-S Yang C Hsu H C Toh R J Epstein L-T Hsiao P-J Chen Z-Z Lin T-Y Chao A-L Cheng 《British journal of cancer》2010,102(6):981-986
Background:
Molecularly targeted agents with anti-angiogenic activity, including bevacizumab, have demonstrated clinical activity in patients with advanced/metastatic hepatocellular carcinoma (HCC). This multicentre phase II study involving patients from several Asian countries sought to evaluate the safety and efficacy of bevacizumab plus capecitabine in this population.Methods:
Histologically proven/clinically diagnosed advanced HCC patients received bevacizumab 7.5 mg kg–1 on day 1 and capecitabine 800 mg m–2 twice daily on days 1–14 every 3 weeks as first-line therapy.Results:
A total of 45 patients were enrolled; 44 (96%) had extrahepatic metastasis and/or major vessel invasion and 30 (67%) had hepatitis B. No grade 3/4 haematological toxicity occurred. Treatment-related grade 3/4 non-haematological toxicities included diarrhoea (n=2, 4%), nausea/vomiting (n=1, 2%), gastrointestinal bleeding (n=4, 9%) and hand–foot syndrome (n=4, 9%). The overall response rate (RECIST) was 9% and the disease control rate was 52%. Overall, median progression-free survival (PFS) and overall survival (OS) were 2.7 and 5.9 months, respectively. Median PFS and OS were 3.6 and 8.2 months, respectively, for Cancer of the Liver Italian Programme (CLIP) score ⩽3 patients, and 1.4 and 3.3 months, respectively, for CLIP score 4 patients.Conclusion:
The bevacizumab–capecitabine combination shows good tolerability and modest anti-tumour activity in patients with advanced HCC. 相似文献12.
R Zarate J Rodríguez E Bandres A Pati?o-Garcia M Ponz-Sarvise A Viudez N Ramirez N Bitarte A Chopitea J Gacía-Foncillas 《British journal of cancer》2010,102(6):987-994
Background:
A dose-finding study was performed to evaluate the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD) and the recommended dose (RD) of escalating the doses of capecitabine and fixed doses of irinotecan and oxaliplatin on a biweekly schedule for metastatic colorectal cancer patients (mCRC). A pharmacogenomic analysis was performed to investigate the association between SNPs and treatment outcome.Methods:
Eighty-seven chemotherapy-naïve mCRC patients were recruited through a two-step study design; 27 were included in the dose-finding study and 60 in the pharmacogenomic analysis. Oxaliplatin (85 mg m-2) and CPT-11 (150 mg m-2), both on day 1, and capecitabine doses ranging from 850 to 1500 mg m-2 bid on days 1–7 were explored. Peripheral blood samples were used to genotype 13 SNPs in 10 genes related to drug metabolism or efficacy. Univariate and multivariate Cox analysis was performed to examine associations between SNPs, ORR and PFS.Results:
The capecitabine RD was 1000 mg m−2 bid. Diarrhoea and neutropenia were the DLTs. After a median follow-up of 52.5 months, the median PFS and OS were 12 (95% CI; 10.6–13.4) and 27 months (95% CI; 17.2–36.8), respectively.The GSTP1-G genotype, the Köhne low-risk category and use of a consolidation approach strongly correlated with decreased risk of progression. Patients with all favourable variables showed a median PFS of 42 months vs 3.4 months in the group with all adverse factors. A superior clinical response was obtained in patients with one GSTP1-G allele as compared with GSTP1-AA carriers (P=0.004).Conclusion:
First-line therapy with oxaliplatin, irinotecan and capecitabine is efficient and well-tolerated. The GSTP1 polymorphism A>G status was significantly associated with ORR and PFS in mCRC treated with this triplet therapy. 相似文献13.
Background:
The purpose of the study was to evaluate the cost-effectiveness of capecitabine plus oxaliplatin (XELOX) compared with 5-fluorouracil/folinic acid and oxaliplatin (FOLFOX4) as first-line or second-line chemotherapy in patients with metastatic colorectal cancer.Methods:
On the basis of NO16966 and NO16967 trials, mean costs and effectiveness were calculated from patient-level data. Until the disease progressed, the mean costs were calculated from the perspective of health-care payers in Japan. We estimated mean quality-adjusted progression-free survival days (QAPFSD), considering adverse events and patient preference for chemotherapy regimens. Utility scores were obtained by a web-based survey from general people, randomly sampled from a large panel adjusted for sex and age.Results:
Incremental effectiveness of XELOX as first-line and second-line chemotherapy for colorectal cancer patients was significantly greater. By use of XELOX, patients gained 10.5 QAPFSD from first-line treatment or 11.3 QAPFSD from second-line treatment. Capecitabine plus oxaliplatin (XELOX) was also proven to significantly reduce treatment costs by €3000 (JPY 360 000) and €2300 (JPY 270 000) for first-line and second-line treatment, respectively. In health-care settings in the United Kingdom, XELOX decreased medical costs for National Health Service by £7600 and £3900 for patients who received first-line and second-line treatment, respectively.Conclusion:
Capecitabine plus oxaliplatin (XELOX) as first-line and second-line chemotherapy was ‘dominant''. In terms of effectiveness and cost, XELOX was superior to FOLFOX4. 相似文献14.
A J Weickhardt D S Williams C K Lee F Chionh J Simes C Murone K Wilson M M Parry K Asadi A M Scott C J A Punt I D Nagtegaal T J Price J M Mariadason N C Tebbutt 《British journal of cancer》2015,113(1):37-45
Background:
Bevacizumab prolongs progression-free survival (PFS) in patients with metastatic colorectal cancer. We analysed the protein expression levels of vascular endothelial growth factor (VEGF) ligands and receptors to determine their prognostic and predictive effects.Methods:
We graded expression of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, and VEGF-R2 to assess whether overexpression predicted bevacizumab resistance in samples from 268 of 471 patients randomised to capecitabine (C), capecitabine and bevacizumab (CB), or CB and mitomycin (CBM) in the MAX trial and extended the analysis to the CAIRO-2 population.Results:
Patients with low expression of VEGF-D (0, 1+) benefited from bevacizumab treatment (PFS hazard ratio (HR) (C vs CB+CBM), 0.21; 95% CI, 0.08–0.55; overall survival (OS) HR, 0.35; 95% CI, 0.13–0.90). Patients with higher VEGF-D expression received less benefit (VEGF-D 2+ PFS HR, 0.67; 95% CI, 0.45–1.00; OS HR, 0.82; 95% CI, 0.52–1.30; VEGF-D 3+ PFS HR, 0.77; 95% CI, 0.50–1.17; OS HR, 1.28; 95% CI, 0.79–2.09) (P interaction <0.05). In CAIRO-2, there was no difference in PFS or OS according to VEGF-D expression.Conclusions:
The predictive value of VEGF-D expression for bevacizumab may depend on the chemotherapy backbone used. Further evaluation is required before clinical utilisation. 相似文献15.
Souglakos J Ziras N Kakolyris S Boukovinas I Kentepozidis N Makrantonakis P Xynogalos S Christophyllakis Ch Kouroussis Ch Vamvakas L Georgoulias V Polyzos A 《British journal of cancer》2012,106(3):453-459
Background:
To compare the efficacy and safety of CAPIRI+bevacizumab (Bev) in comparison with FOLFIRI+Bev as first-line treatment for patients with metastatic colorectal cancer (mCRC).Methods:
Patients were randomised to receive either FOLFIRI plus Bev 5 mg kg−1 every 2 weeks (Arm-A) or CAPIRI plus Bev 7.5 mg kg−1 every 3 weeks (Arm-B).Results:
Three hundred thirty-three patients (Arm-A=167; Arm-B=166) were enrolled into the study. No difference was observed in median progression-free survival (PFS) (10.0 and 8.9 months; P=0.64), overall survival (25.7 and 27.5 months; P=0.55) or response rates (45.5 and 39.8.7% P=0.32) for FOLFIRI-Bev and CAPIRI-Bev, respectively. Patients treated with CAPIRI-Bev presented significantly higher incidence of diarrhoea (P=0.005), febrile neutropenia (P=0.003) and hand–foot skin reactions (P=0.02) compared with patients treated with FOLFIRI-Bev. Treatment delays (P=0.05), dose reduction (P<0.001) and treatment discontinuation owing to toxicity (P=0.01) occurred more frequently in the CAPIRI-Bev arm.Conclusion:
The PFS of FOLFIRI-BEV is not superior to that observed with the CAPIRI-Bev regimen. CAPIRI-Bev has a less favourable toxicity profile, requiring dose reductions, in order to be considered as an option in first-line treatment of patients with mCRC. 相似文献16.
T Conroy M Hebbar J Bennouna M Ducreux M Ychou G Ll��do A Adenis R Faroux C Rebischung L Kockler J Y Douillard 《British journal of cancer》2010,102(1):59-67
Background:
A phase-III trial showed the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) in terms of efficacy in first-line treatment of metastatic colorectal cancer. A secondary objective was to compare the quality of life (QoL) and health-care satisfaction of patients.Methods:
Patients were randomised to receive XELOX (n=156) or FOLFOX-6 (n=150) for 6 months. Quality of life and satisfaction were assessed by the Quality of Life Questionnaire-C30 (QLQ-C30) and Functional Assessment of Chronic Illness Therapy Chemotherapy Convenience and Satisfaction Questionnaire (FACIT-CCSQ), respectively. Patients completed questionnaires at baseline, at Cycle3 (C3) and Cycle (C6) (XELOX) or at C4 and C8 visits (FOLFOX-6) and at their final visit.Results:
A total of 245 and 225 patients were assessed using QLQ-C30 and FACIT-CCSQ, respectively. The completion rates were >80%. Global QoL scores did not differ significantly between groups during the study. According to FACIT-CCSQ, XELOX seemed more convenient (C3/C4, P<0.001; C6/C8, P=0.009) and satisfactory to patients (C6/C8, P=0.003) than FOLFOX-6. At the final visit, XELOX patients spent fewer days on hospital visits (3.3 vs 5.3 days, P=0.045) and lost fewer hours of work/daily activities (10.2 vs 37.1 h lost, P=0.007).Conclusion:
XELOX has a similar QoL profile, but seemed to be more convenient in terms of administration at certain time points and reduced time lost for work or other activities compared with FOLFOX-6. 相似文献17.
Sastre J Maestro ML Gómez-España A Rivera F Valladares M Massuti B Benavides M Gallén M Marcuello E Abad A Arrivi A Fernández-Martos C González E Tabernero JM Vidaurreta M Aranda E Díaz-Rubio E 《The oncologist》2012,17(7):947-955
Background.
The Maintenance in Colorectal Cancer trial was a phase III study to assess maintenance therapy with single-agent bevacizumab versus bevacizumab plus chemotherapy in patients with metastatic colorectal cancer. An ancillary study was conducted to evaluate the circulating tumor cell (CTC) count as a prognostic and/or predictive marker for efficacy endpoints.Patients and Methods.
One hundred eighty patients were included. Blood samples were obtained at baseline and after three cycles. CTC enumeration was carried out using the CellSearch® System (Veridex LLC, Raritan, NJ). Computed tomography scans were performed at cycle 3 and 6 and every 12 weeks thereafter for tumor response assessment.Results.
The median progression-free survival (PFS) interval for patients with a CTC count ≥3 at baseline was 7.8 months, versus the 12.0 months achieved by patients with a CTC count <3 (p = .0002). The median overall survival (OS) time was 17.7 months for patients with a CTC count ≥3, compared with 25.1 months for patients with a lower count (p = .0059). After three cycles, the median PFS interval for patients with a low CTC count was 10.8 months, significantly longer than the 7.5 months for patients with a high CTC count (p = .005). The median OS time for patients with a CTC count <3 was significantly longer than for patients with a CTC count ≥3, 25.1 months versus 16.2 months, respectively (p = .0095).Conclusions.
The CTC count is a strong prognostic factor for PFS and OS outcomes in metastatic colorectal cancer patients. 相似文献18.
D Cunningham R P W Wong G D'Haens J-Y Douillard J Robertson A M Stone E Van Cutsem 《British journal of cancer》2013,108(3):493-502
Background:
Cediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signalling with activity against all three VEGF receptors. Bevacizumab is an anti-VEGF-A monoclonal antibody with clinical benefit in previously treated metastatic colorectal cancer (mCRC).Methods:
Patients with mCRC who had progressed following first-line therapy were randomised 1 : 1 : 1 to modified (m)FOLFOX6 plus cediranib (20 or 30 mg day−1) or bevacizumab (10 mg kg−1 every 2 weeks). The primary objective was to compare progression-free survival (PFS) between treatment arms.Results:
A total of 210 patients were included in the intent-to-treat (ITT) analysis (cediranib 20 mg, n=71; cediranib 30 mg, n=73; bevacizumab, n=66). Median PFS in the cediranib 20 mg, cediranib 30 mg and bevacizumab groups was 5.8, 7.2 and 7.8 months, respectively. There were no statistically significant differences between treatment arms for PFS (cediranib 20 mg vs bevacizumab: HR=1.28 (95% CI, 0.85–1.95; P=0.29); cediranib 30 mg vs bevacizumab: HR=1.17 (95% CI, 0.77–1.76; P=0.79)) or overall survival (OS). Grade ⩾3 adverse events were more common with cediranib 30 mg (91.8%) vs cediranib 20 mg (81.4%) or bevacizumab (84.8%).Conclusion:
There were no statistically significant differences between treatment arms for PFS or OS. When combined with mFOLFOX6, the 20 mg day−1 dose of cediranib was better tolerated than the 30 mg day−1 dose. 相似文献19.
Herbert I. Hurwitz Niall C. Tebbutt Fairooz Kabbinavar Bruce J. Giantonio Zhong‐Zhen Guan Lada Mitchell Daniel Waterkamp Josep Tabernero 《The oncologist》2013,18(9):1004-1012
Purpose.
This analysis pooled individual patient data from randomized controlled trials (RCTs) to more thoroughly examine clinical outcomes when adding bevacizumab to chemotherapy for patients with metastatic colorectal cancer (mCRC).Patients and Methods.
Patient data were pooled from the first-line AVF2107, NO16966, ARTIST, AVF0780, AVF2192, and AGITG MAX RCTs and the second-line E3200 RCT. All analyses were based on the intent-to-treat population. To assess differences in time-to-event variables by treatment (chemotherapy with or without placebo vs. chemotherapy plus bevacizumab), stratified random-effects (overall) and fixed-effects (subgroup comparisons) models were used to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs).Results.
The analysis population comprised 3,763 patients (1,773 chemotherapy with or without placebo; 1,990 chemotherapy plus bevacizumab). The addition of bevacizumab to chemotherapy was associated with statistically significant increases in overall survival (OS; HR, 0.80; 95% CI, 0.71–0.90) and progression-free survival (PFS; HR, 0.57; 95% CI, 0.46–0.71). The effects on OS and PFS across subgroups defined by chemotherapy backbone (oxaliplatin-based, irinotecan-based), extent of disease (liver metastases only, extensive disease), age (<65, ≥65 years), Eastern Cooperative Oncology Group performance status (0, ≥1), and KRAS status (wild-type, mutant) were consistent with the overall analysis. Incidence rates of grade ≥3 hypertension, proteinuria, bleeding, wound-healing complications, gastrointestinal perforations, and thromboembolic events were increased with bevacizumab treatment.Conclusion.
The use of bevacizumab with chemotherapy resulted in statistically significant increases in OS and PFS for patients with mCRC. The PFS benefit extended across the clinically relevant subgroups examined. The observed safety profile of bevacizumab was consistent with that reported in individual trials. 相似文献20.
Stintzing S Fischer von Weikersthal L Vehling-Kaiser U Stauch M Hass HG Dietzfelbinger H Oruzio D Klein S Zellmann K Decker T Schulze M Abenhardt W Puchtler G Kappauf H Mittermüller J Haberl C Giessen C Moosmann N Heinemann V 《British journal of cancer》2011,105(2):206-211