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Huang J, Chen M, Chan VCW, Liu X, Zhong C, Lin J, Hang J, Zhong CC, Yuan J, Wong MCS. The Cost-Effectiveness of a Multi-Target Stool DNA-Based Screening (COLOTECT), FIT, Colonoscopy and No Screening for Colorectal Cancer. Cancer Rep (Hoboken) 2025; 8:e70176. [PMID: 40275466 PMCID: PMC12021674 DOI: 10.1002/cnr2.70176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 02/16/2025] [Accepted: 02/20/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND Around 1.9 million new cases and 1 million deaths worldwide were attributed to colorectal cancer (CRC) in 2020. AIMS The aims of this study are to assess the cost-effectiveness of a multi-target stool DNA-based screening strategy, COLOTECT, compared to faecal immunochemical tests (FIT), colonoscopy, and no screening in the Asian population to inform more choices for policymakers in colorectal cancer screening. METHOD AND RESULTS We assume that 100,000 persons aged 50 undergo annual FIT, annual COLOTECT multi-target testing, or colonoscopies every 10 years until age 75. The data used in this study was retrieved from different sources including the Hong Kong Cancer Registry and previously published studies on the population aged 50 to 75 years old between 2010 and 2023. This study accessed the most cost-effective screening strategy available. If a positive result of FIT or COLOTECT were observed, the participants would undergo a colonoscopy. The participants who used the colonoscopy as the main screening method conducted colonoscopies every 3 years. The Markov models were utilized to compare the outcomes from different strategies including life-years saved, years of life lost, and incremental cost-effectiveness ratio (primary outcome). The highest ICER was observed in colonoscopy (USD 160808), followed by FIT (USD 108952), and COLOTECT (USD 82206). A higher detection rate of CRC (COLOTECT: 39.3% vs. FIT: 4.5%), more CRC cases prevented (1272 vs. 146), and life-years saved (2295 vs. 337) were observed in the COLOTECT strategy than in FIT. Additionally, a lower total cost per life-year saved of COLOTECT (USD 180097) was observed than colonoscopy (USD 238356), which identified the more affordable and cost-saving COLOTECT strategy. CONCLUSION This study highlighted the better performance of COLOTECT than FIT in detecting CRC. Additionally, given its lower cost and higher acceptance, the COLOTECT strategy might be more cost-effective than colonoscopy for massive CRC screening.
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Affiliation(s)
- Junjie Huang
- Jockey Club School of Public Health and Primary Care, Faculty of MedicineThe Chinese University of Hong KongHong Kong SAR
- Centre for Health Education and Health Promotion, Faculty of MedicineThe Chinese University of Hong KongHong Kong SAR
| | - Mingtao Chen
- Jockey Club School of Public Health and Primary Care, Faculty of MedicineThe Chinese University of Hong KongHong Kong SAR
| | - Victor C. W. Chan
- Jockey Club School of Public Health and Primary Care, Faculty of MedicineThe Chinese University of Hong KongHong Kong SAR
| | - Xianjing Liu
- Department of Radiology and Nuclear MedicineErasmus MC University Medical CenterRotterdamthe Netherlands
| | - Chaoying Zhong
- Department of Electrical Engineering and AutomationGuangdong Ocean UniversityZhanjiangGuangdongChina
| | - Jianli Lin
- Peking‐Tsinghua Center for Life SciencesAcademy for Advanced Interdisciplinary Studies, Peking UniversityBeijingChina
| | - Junjie Hang
- Cancer Hospital & Shenzhen HospitalBeijingChinese Academy of Medical Sciences and Peking Union Medical CollegeChina
| | - Claire Chenwen Zhong
- Jockey Club School of Public Health and Primary Care, Faculty of MedicineThe Chinese University of Hong KongHong Kong SAR
- Centre for Health Education and Health Promotion, Faculty of MedicineThe Chinese University of Hong KongHong Kong SAR
| | - Jinqiu Yuan
- Clinical Research Center, Big Data CenterThe Seventh Afliated Hospital, Sun Yat‐Sen UniversityGuangzhouGuangdongChina
| | - Martin C. S. Wong
- Jockey Club School of Public Health and Primary Care, Faculty of MedicineThe Chinese University of Hong KongHong Kong SAR
- Centre for Health Education and Health Promotion, Faculty of MedicineThe Chinese University of Hong KongHong Kong SAR
- The School of Public HealthPeking UniversityBeijingChina
- The School of Public HealthThe Chinese Academy of Medical Sciences and The Peking Union Medical CollegesBeijingChina
- The School of Public HealthFudan UniversityShanghaiChina
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Huang J, Chan VCW, Chen M, Liew JJM, Liu X, Zhong C, Lin J, Hang J, Zhong CC, Yuan J, Xu W, Withers M, Chan AT, Wong MCS. Revisiting the starting age of colorectal cancer screening for the average-risk Asian population: a cost-effectiveness analysis. Gastrointest Endosc 2025:S0016-5107(25)00141-5. [PMID: 40024296 DOI: 10.1016/j.gie.2025.02.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/07/2025] [Accepted: 02/21/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND AND AIMS One of the most prevalent and fatal tumors, colorectal cancer (CRC), has a significant impact on the use of healthcare services. Although Hong Kong's CRC screening program has been successful, it does not prioritize preventing early-onset CRC in people under age 50 years. This study aimed to assess the cost-effectiveness of different starting ages for CRC screening among an Asian population. METHODS We conducted a simulation study involving 100,000 individuals in Hong Kong who were screened using either the fecal immunochemical test (FIT) or colonoscopy as primary screening methods at ages 40, 45, and 50 until age 75. The performance of different strategies was evaluated based on life-years gained, and cost-effectiveness was measured using the incremental cost-effectiveness ratio (ICER). RESULTS The ICERs for initiating FIT screening at age 50, screening starting at age 45, and screening starting at age 40 were U.S. dollars (USD) 53,262, USD 67,892, and USD 86,554, respectively. For colonoscopy, the ICERs for initiating screening at ages 50, 45, and 40 were USD 267,669, USD 312,848, and USD 372,090, respectively. Overall, the FIT strategy was found to be less costly. At 70%, 80%, and 90% compliance rates, the FIT at age 45 gained 2135, 2296, and 2438 life-years, respectively, whereas colonoscopy at age 45 gained 2725, 2798, and 2855 life-years, respectively. With increased compliance rates, the FIT could save a similar number of life-years as colonoscopy with lower cost. CONCLUSIONS Initiating CRC screening at age 45 using the FIT in Hong Kong was determined to be a well-balanced and cost-effective strategy. This approach demonstrated a cost advantage over starting screening at age 40 and resulted in more lives saved compared with screening at age 50.
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Affiliation(s)
- Junjie Huang
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR; Centre for Health Education and Health Promotion, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR
| | - Victor C W Chan
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR
| | - Mingtao Chen
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR
| | - Jamie Jie Mei Liew
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR
| | - Xianjing Liu
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Chaoying Zhong
- Department of Electrical Engineering and Automation, Guangdong Ocean University, Guangdong, China
| | - Jianli Lin
- Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
| | - Junjie Hang
- Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Guangdong, China
| | - Claire Chenwen Zhong
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR; Centre for Health Education and Health Promotion, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR.
| | - Jinqiu Yuan
- Clinical Research Center, Big Data Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Guangdong, China
| | - Wanghong Xu
- The School of Public Health, Fudan University, Shanghai, China
| | - Mellissa Withers
- Department of Population and Health Sciences, Institute for Global Health, University of Southern California, Los Angeles, California, USA
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
| | - Martin C S Wong
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR; Centre for Health Education and Health Promotion, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR; The School of Public Health, Fudan University, Shanghai, China; The School of Public Health, Peking University, Beijing, China; The School of Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Guangdong, China.
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Wong MCS, Huang J, Wong YY, Ko S, Chan VCW, Ng SC, Chan FKL. The Use of a Non-Invasive Biomarker for Colorectal Cancer Screening: A Comparative Cost-Effectiveness Modeling Study. Cancers (Basel) 2023; 15:cancers15030633. [PMID: 36765591 PMCID: PMC9913459 DOI: 10.3390/cancers15030633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/17/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
This study aimed to examine the cost-effectiveness of fecal biomarker M3 panel compared to fecal immunochemical test (FIT) and colonoscopy in an Asian population. In a hypothetical population of 100,000 persons aged 50 years who received FIT yearly, M3 biomarker yearly, or colonoscopy every 10 years until the age of 75 years. Participants with positive FOBT or a result of "high risk" identified using the M3 biomarker are offered colonoscopy. We assumed surveillance colonoscopy is repeated every 3 years, and examined the treatment cost. A comparison of various outcome measures was conducted using Markov modelling. The incremental cost-effectiveness ratio (ICER) of FIT, M3 biomarker, and colonoscopy was USD108,176, USD133,485 and USD159,596, respectively. Comparing with FIT, the use of M3 biomarker could lead to significantly smaller total loss of cancer-related life-years (2783 vs. 5279); a higher number of CRC cases prevented (1622 vs. 146), a higher proportion of CRC cases prevented (50.2% vs. 4.5%), more life-years saved (2852 vs. 339), and cheaper total costs per life-year saved (USD212,553 vs. 773,894). The total costs per life-year saved is more affordable than that achieved by colonoscopy as a primary screening tool (USD212,553 vs. USD236,909). The findings show that M3 biomarkers may be more cost-effective than colonoscopy.
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Affiliation(s)
- Martin C. S. Wong
- JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- Centre for Health Education and Health Promotion, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Junjie Huang
- JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- Centre for Health Education and Health Promotion, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Yuet-Yan Wong
- JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Samantha Ko
- JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Victor C. W. Chan
- JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Siew C. Ng
- Centre for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- The Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- Correspondence: (S.C.N.); (F.K.L.C.); Tel.: +852-3505-1339 (F.K.L.C.); Fax: +852-2647-1557 (F.K.L.C.)
| | - Francis K. L. Chan
- Centre for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- The Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- Correspondence: (S.C.N.); (F.K.L.C.); Tel.: +852-3505-1339 (F.K.L.C.); Fax: +852-2647-1557 (F.K.L.C.)
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Hurwitz HI, Tan BR, Reeves JA, Xiong H, Somer B, Lenz HJ, Hochster HS, Scappaticci F, Palma JF, Price R, Lee JJ, Nicholas A, Sommer N, Bendell J. Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM). Oncologist 2018; 24:921-932. [PMID: 30552157 DOI: 10.1634/theoncologist.2018-0344] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 11/06/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND First-line treatment for metastatic colorectal cancer (mCRC) typically entails a biologic such as bevacizumab (BEV) with 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) or 5-fluorouracil/leucovorin/irinotecan (FOLFIRI). STEAM (NCT01765582) assessed the efficacy of BEV plus FOLFOX/FOLFIRI (FOLFOXIRI), administered concurrently (cFOLFOXIRI-BEV) or sequentially (sFOLFOXIRI-BEV, FOLFOX-BEV alternating with FOLFIRI-BEV), versus FOLFOX-BEV for mCRC. PATIENTS AND METHODS Patients with previously untreated mCRC (n = 280) were randomized 1:1:1 to cFOLFOXIRI-BEV, sFOLFOXIRI-BEV, or FOLFOX-BEV and treated with 4-6-month induction followed by maintenance. Coprimary objectives were overall response rate (ORR; first-line cFOLFOXIRI-BEV vs. FOLFOX-BEV) and progression-free survival (PFS; pooled first-line cFOLFOXIRI-BEV and sFOLFOXIRI-BEV vs. FOLFOX-BEV). Secondary/exploratory objectives included overall survival (OS), liver resection rates, biomarker analyses, and safety. RESULTS ORR was 72.0%, 72.8%, and 62.1% and median PFS was 11.9, 11.4, and 9.5 months with cFOLFOXIRI-BEV, sFOLFOXIRI-BEV, and FOLFOX-BEV, respectively. OS was similar between arms. ORR between cFOLFOXIRI-BEV and FOLFOX-BEV did not significantly differ (p = .132); thus, the primary ORR endpoint was not met. cFOLFOXIRI-BEV and sFOLFOXIRI-BEV numerically improved ORR and PFS, regardless of RAS status. Median PFS was higher with pooled concurrent and sequential FOLFOXIRI-BEV versus FOLFOX-BEV (11.7 vs. 9.5 months; hazard ratio, 0.7; 90% confidence interval, 0.5-0.9; p < .01). Liver resection rates were 17.2% (cFOLFOXIRI-BEV), 9.8% (sFOLFOXIRI-BEV), and 8.4% (FOLFOX-BEV). Grade ≥ 3 treatment-emergent adverse events (TEAEs) were observed in 91.2% (cFOLFOXIRI-BEV), 86.7% (sFOLFOXIRI-BEV), and 85.6% (FOLFOX-BEV) of patients, with no increase in serious chemotherapy-associated TEAEs. CONCLUSION cFOLFOXIRI-BEV and sFOLFOXIRI-BEV were well tolerated with numerically improved ORR, PFS, and liver resection rates versus FOLFOX-BEV, supporting triplet chemotherapy plus BEV as a first-line treatment option for mCRC. IMPLICATIONS FOR PRACTICE: The combination of first-line FOLFIRI with FOLFOX and bevacizumab (concurrent FOLFOXIRI-BEV) improves clinical outcomes in patients with metastatic colorectal cancer (mCRC) relative to FOLFIRI-BEV or FOLFOX-BEV, but it is thought to be associated with increased toxicity. Alternating treatment of FOLFOX and FOLFIRI (sequential FOLFOXIRI-BEV) could improve tolerability. In the phase II STEAM trial, which is the largest study of FOLFOXIRI-BEV in patients in the U.S., it was found that both concurrent and sequential FOLFOXIRI-BEV are active and well tolerated in patients with previously untreated mCRC, supporting the use of these regimens as potential first-line treatment options for this population.
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Affiliation(s)
| | - Benjamin R Tan
- Washington University School of Medicine, Saint Louis, Missouri, USA
| | - James A Reeves
- Florida Cancer Specialists - South Region, Ft. Myers, Florida, USA
| | - Henry Xiong
- The Center for Cancer and Blood Disorders, Fort Worth, Texas, USA
| | | | - Heinz-Josef Lenz
- USC Norris Comprehensive Cancer Center, Los Angeles, California, USA
| | - Howard S Hochster
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
| | | | - John F Palma
- Roche Sequencing Solutions, Pleasanton California, USA
| | - Richard Price
- Genentech, Inc., South San Francisco, California, USA
| | - John J Lee
- Roche Sequencing Solutions, Pleasanton California, USA
| | - Alan Nicholas
- Genentech, Inc., South San Francisco, California, USA
| | | | - Johanna Bendell
- Sarah Cannon Research Institute/Tennessee Oncology, Nashville, Tennessee, USA
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Lakdawalla D, Shafrin J, Lucarelli C, Nicholson S, Khan ZM, Philipson TJ. Quality-adjusted cost of care: a meaningful way to measure growth in innovation cost versus the value of health gains. Health Aff (Millwood) 2016; 34:555-61. [PMID: 25847636 DOI: 10.1377/hlthaff.2014.0639] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Technology drives both health care spending and health improvement. Yet policy makers rarely see measures of cost growth that account for both effects. To fill this gap, we present the quality-adjusted cost of care, which illustrates cost growth net of growth in the value of health improvements, measured as survival gains multiplied by the value of survival. We applied the quality-adjusted cost of care to two cases. For colorectal cancer, drug cost per patient increased by $34,493 between 1998 and 2005 as a result of new drug launches, but value from offsetting health improvements netted a modest $1,377 increase in quality-adjusted cost of care. For multiple myeloma, new therapies increased treatment cost by $72,937 between 2004 and 2009, but offsetting health benefits lowered overall quality-adjusted cost of care by $67,863. However, patients with multiple myeloma on established first-line therapies saw costs rise without corresponding benefits. All three examples document rapid cost growth, but they provide starkly different answers to the question of whether society got what it paid for.
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Affiliation(s)
- Darius Lakdawalla
- Darius Lakdawalla is the Quintiles Professor of Pharmaceutical Development and Regulatory Innovation at the Schaeffer Center for Health Policy and Economics, University of Southern California, in Los Angeles
| | - Jason Shafrin
- Jason Shafrin is a senior research economist at Precision Health Economics, in Los Angeles
| | - Claudio Lucarelli
- Claudio Lucarelli is a professor of economics at Universidad de los Andes, in Santiago, Chile
| | - Sean Nicholson
- Sean Nicholson is a professor in the Department of Policy Analysis and Management at Cornell University, in Ithaca, New York
| | - Zeba M Khan
- Zeba M. Khan is vice president of Corporate Responsibility at Celgene Corporation, in Summit, New Jersey
| | - Tomas J Philipson
- Tomas J. Philipson is the Daniel Levin Professor of Public Policy at the Irving B. Harris Graduate School for Public Policy Studies, University of Chicago, in Illinois
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Petrelli F, Coinu A, Ghilardi M, Cabiddu M, Zaniboni A, Barni S. Efficacy of oxaliplatin-based chemotherapy + bevacizumab as first-line treatment for advanced colorectal cancer: a systematic review and pooled analysis of published trials. Am J Clin Oncol 2015; 38:227-33. [PMID: 25806713 DOI: 10.1097/coc.0b013e3182a2d7b8] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Oxaliplatin and either capecitabine or infusional/bolus 5-fluorouracil (5FU)-based chemotherapy + bevacizumab (XELOX + B and FOLFOX + B) represent 2 of the approved first-line treatments for advanced colorectal cancer (CRC). However, the addition of B did not offer a survival benefit compared with FOLFOX/XELOX alone in the phase III, NO16966 trial. The aim of this review was to aggregate all published data on the efficacy of XELOX and FOLFOX-B in prospective and retrospective studies as first-line therapy for stage IV CRC. METHODS We performed a systematic review, through PubMed and EMBASE, of all published studies exploring the efficacy of fluoropyrimidines + oxaliplatin + B-based chemotherapy as first-line chemotherapy in advanced CRC patients. Pooled estimates of the response rates, weighted medians of progression-free survival, and overall survival from all FOLFOX + B and XELOX + B arms were calculated. RESULTS A total of 25 studies were retrieved, with a total of 7878 patients. Overall, the pooled response rates (n=20 publications) was 49.1%. The median progression-free survival and overall survival (n=21 and 22 publications, respectively) were 10.3 and 23.7 months, respectively. The pooled median rate of surgical resection of metastases (n=13 publications) was 14%. CONCLUSIONS XELOX + B and FOLFOX + B are active combinations as first-line treatment of advanced CRC. The efficacy is confirmed for the first time from this pooled analysis of 25 trials. Both the XELOX + B and the FOLFOX + B arms represent 2 of the cornerstone combinations when B is used as first-line therapy.
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Affiliation(s)
- Fausto Petrelli
- *Oncology Department, Medical Oncology Unit, Azienda Ospedaliera Treviglio-Caravaggio, Treviglio (BG) †UO Oncologia, Dipartimento Oncologico, Istituto Ospedaliero Fondazione Poliambulanza, Brescia (BS), Italy
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Park LC, Lee HS, Shin SH, Park SJ, Park MI, Oh SY, Kwon HC, Baek JH, Choi YJ, Kang MJ, Kim YS. Bevacizumab as a second- or later-line of treatment for metastatic colorectal cancer. World J Gastroenterol 2012; 18:1104-9. [PMID: 22416186 PMCID: PMC3296985 DOI: 10.3748/wjg.v18.i10.1104] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2011] [Revised: 01/12/2012] [Accepted: 02/08/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the efficacy of bevacizumab in patients with metastatic colorectal cancer (MCRC) who have failed prior chemotherapy without bevacizumab.
METHODS: Between March 2002 and June 2010, 40 patients in South Korea with MCRC who were treated with bevacizumab plus chemotherapy as a second or later-line treatment were analyzed retrospectively for their overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). The tumor responses were assessed using the Response Evaluation Criteria in Solid Tumors guidelines.
RESULTS: All of the patients had progressed under prior chemotherapy without bevacizumab. Three patients (7.5%) exhibited an ORR, twenty one patients (52.5%) exhibited stable disease (SD), and fifteen patients (37.5%) exhibited disease progression. The median duration of the OS and PFS were 14.0 mo and 6.13 mo respectively. The median OSs were 16.60, 14.07 and 13.00 mo for second-line, third-line and fourth- or later-line treatments, respectively. The median PFSs were 7.23, 7.30 and 3.87 mo for the second-line, third-line and fourth- or later-line treatments, respectively.
CONCLUSION: In patients with MCRC, bevacizumab combined chemotherapy may be beneficial during second- or later-line treatment.
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Li S, Chi P. Optimizing the efficacy of first-line chemotherapy plus bevacizumab in metastatic colorectal cancer: analysis of multiple methods. BioDrugs 2011; 25:43-50. [PMID: 21080747 DOI: 10.2165/11584680-000000000-00000] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
OBJECTIVE To assess the efficacy and safety of first-line standard chemotherapy plus bevacizumab in metastatic colorectal cancer and to explore how to optimize therapeutic efficacy. DESIGN First, meta-analysis and pooled analysis of three randomized, controlled trials were used to compare response rate (RR), progression-free survival (PFS), overall survival (OS), and grade 3 or 4 adverse events (G3/4AEs) of chemotherapy plus bevacizumab (n = 1169) with those of chemotherapy alone (n = 1148). Second, using six different regimens plus bevacizumab, the Spearman method was used to analyze the correlation between these regimens and OS. Finally, one-way ANOVA was used to compare OS in these regimens. RESULTS Overall, chemotherapy plus bevacizumab increased RR by 3.8%, prolonged PFS by 3.0 months and OS by 3.3 months, and increased G3/4AEs by 7.6%. Significant differences were found in PFS (hazard ratio [HR] = 0.65; p = 0.000), OS (HR = 0.79; p = 0.000), and G3/4AEs (risk ratio = 1.12; p = 0.006). However, no statistical difference was found in RR (odds ratio = 1.32; p = 0.17). The optimal regimens with regard to mean OS were capecitabine and irinotecan (CAPIRI) plus bevacizumab (24.00 months) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab (23.97 months). CONCLUSION First-line standard chemotherapy plus bevacizumab conferred a significant improvement in OS. In combination with bevacizumab, both CAPIRI and FOLFOX are favorable regimens, though further studies are needed to confirm these results.
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Affiliation(s)
- Shaotang Li
- Postgraduate School, Fujian Medical University, Fuzhou, Fujian, Peoples Republic of China
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Chicca A, Tebano M, Adinolfi B, Ertugrul K, Flamini G, Nieri P. Anti-proliferative activity of aguerin B and a new rare nor-guaianolide lactone isolated from the aerial parts of Centaurea deflexa. Eur J Med Chem 2011; 46:3066-70. [DOI: 10.1016/j.ejmech.2011.03.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2010] [Revised: 01/11/2011] [Accepted: 03/05/2011] [Indexed: 11/17/2022]
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Song X, Zhao Z, Barber B, Gregory C, Wang PF, Long SR. Treatment patterns and metastasectomy among mCRC patients receiving chemotherapy and biologics. Curr Med Res Opin 2011; 27:123-30. [PMID: 21128878 DOI: 10.1185/03007995.2010.536912] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Several long-standing chemotherapy regimens are available to treat metastatic colorectal cancer (mCRC) including: oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin (FOLFOX); and irinotecan plus 5-FU and leucovorin (FOLFIRI). More recently, new biologic therapies were approved for use in mCRC. OBJECTIVES This study examined treatment patterns and trends in metastasectomy among newly diagnosed mCRC patients after the introduction of capecitabine (CAP) in 2001 and the biologic therapies in 2004. METHODS Using a large, US-based administrative medical claims database of a national commercially insured population, patients with newly diagnosed mCRC were identified from 2001 to 2005. At least 6 months of patient history prior to mCRC diagnosis were required to confirm patients were newly diagnosed. Patients were followed from initial mCRC diagnosis to death, disenrollment, or 12/31/2006. Chemotherapy and biologic treatments and rates of metastasectomy over time were analyzed. RESULTS A total of 3781 mCRC patients met the study criteria. The average time from mCRC diagnosis to initiation of systemic treatment decreased from 134.4 days (SD 261.2) to 61.7 days (SD 89.3) in 2001-2005 (p < 0.001). The most common first-line regimens were FOLFIRI (40%), 5-FU/LV (31%), and capecitabine (21%) in 2001, and FOLFOX plus bevacizumab (22%), FOLFOX alone (15%), 5-FU/LV (15%), and capecitabine (15%) in 2005. Among patients with ≥1 year of follow-up, the use of biologics increased from 37.3% in 2004 to 52.0% in 2005 (p < 0.001). The percentage of patients who underwent resection after systemic treatment increased from 2.9% to 5.6% in 2001-2005 (p = 0.169). CONCLUSIONS Over time the standard of care chemotherapy for 1st-line mCRC has changed from FOLFIRI to FOLFOX, and the use of biologics has become common. The percentage of patients who underwent resection after systemic treatment almost doubled during the study period.
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Affiliation(s)
- Xue Song
- Healthcare & Science, Thomson Reuters, Washington, DC, USA.
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Waddell JA, Solimando DA. Leucovorin, Fluorouracil, and Oxaliplatin (FOLFOX) Regimens plus Bevacizumab for Colorectal Cancer. Hosp Pharm 2010. [DOI: 10.1310/hpj4509-685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
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Affiliation(s)
- J. Aubrey Waddell
- University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804
| | - Dominic A. Solimando
- Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203
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Hong YS, Cho HJ, Kim SY, Jung KH, Park JW, Choi HS, Oh JH, Kim BC, Sohn DK, Kim DY, Chang HJ. Carbonic anhydrase 9 is a predictive marker of survival benefit from lower dose of bevacizumab in patients with previously treated metastatic colorectal cancer. BMC Cancer 2009; 9:246. [PMID: 19619339 PMCID: PMC2719665 DOI: 10.1186/1471-2407-9-246] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2009] [Accepted: 07/21/2009] [Indexed: 12/13/2022] Open
Abstract
Background Carbonic anhydrase 9 (CA9) is a marker for hypoxia and acidosis, which is linked to a poor prognosis in human tumors. The purpose of this comparative analysis was to evaluate whether CA9 and VEGF expression are associated with survival outcomes in patients with metastatic colorectal cancer (mCRC) after treatment with bevacizumab as second or later line treatment. Methods Thirty-one mCRC patients who were treated with bevacizumab-containing chemotherapy as second or later line treatment and who had analyzable tumor paraffin blocks were selected for this study. The planned dose of bevacizumab was 5 mg/kg/2-week. Immunohistochemical (IHC) staining of CA9 and VEGF was performed and their expression was scored by the intensity multiplied by percentage of stained area. Results The overall response rate was 19.4% and the disease control rate (DCR) was 61.3% with 6 partial responses and 13 cases of stable disease. The DCR was significantly higher in patients with a lower CA9 expression score compared to those with a higher score (80.0% vs. 27.3%, respectively, P = 0.004). The patients with a low CA9 expression score also showed better outcomes with regard to the median progression-free survival (P = 0.028) and overall survival (P = 0.026). However, VEGF expression was not associated with the DCR and survival. Conclusion Lower degree of CA9 expression was associated with better clinical outcomes in patients with mCRC treated with lower dose bevacizumab-based chemotherapy. Prospective studies are now needed to determine the correlation between CA9 expression and clinical outcomes after bevacizumab treatment, at different doses and in varied settings.
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Affiliation(s)
- Yong Sang Hong
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
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Baker JHE, Lam J, Kyle AH, Sy J, Oliver T, Co SJ, Dragowska WH, Ramsay E, Anantha M, Ruth TJ, Adam MJ, Yung A, Kozlowski P, Minchinton AI, Ng SSW, Bally MB, Yapp DTT. Irinophore C, a novel nanoformulation of irinotecan, alters tumor vascular function and enhances the distribution of 5-fluorouracil and doxorubicin. Clin Cancer Res 2009; 14:7260-71. [PMID: 19010842 DOI: 10.1158/1078-0432.ccr-08-0736] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE To examine the antitumor effects of Irinophore C, a nanopharmaceutical formulation of irinotecan, on the tissue morphology and function of tumor vasculature in HT-29 human colorectal tumors. EXPERIMENTAL DESIGN Fluorescence microscopy was used to map and quantify changes in tissue density, tumor vasculature, hypoxia, and the distribution of Hoechst 33342, a perfusion marker, and the anticancer drug, doxorubicin. Noninvasive magnetic resonance imaging was used to quantify Ktrans, the volume transfer constant of a solute between the blood vessels and extracellular tissue compartment of the tumor, as a measure of vascular function. Following treatment with Irinophore C, 19F magnetic resonance spectroscopy was used to monitor the delivery of 5-fluorouracil (5-FU) to the tumor tissue, whereas scintigraphy was used to quantify the presence of bound [14C]5-FU. RESULTS Irinophore C decreased cell density (P = 8.42 x 10(-5)), the overall number of endothelial cells in the entire section (P = 0.014), tumor hypoxia (P = 5.32 x 10(-9)), and K(trans) (P = 0.050). However, treatment increased the ratio of endothelial cells to cell density (P = 0.00024) and the accumulation of Hoechst 33342 (P = 0.022), doxorubicin (P = 0.243 x 10(-5)), and 5-FU (P = 0.0002) in the tumor. Vascular endothelial growth factor and interleukin-8, two proangiogenic factors, were down-regulated, whereas the antiangiogenic factor TIMP-1 was up-regulated in Irinophore C-treated tumors. CONCLUSIONS Irinophore C treatment improves the vascular function of the tumor, thereby reducing tumor hypoxia and increasing the delivery and accumulation of a second drug. Reducing hypoxia would enhance radiotherapy, whereas improving delivery of a second drug to the tumor should result in higher cell kill.
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Affiliation(s)
- Jennifer H E Baker
- Medical Biophysics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
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Abstract
BACKGROUND Faecal occult blood testing (FOBT), flexible sigmoidoscopy (FS) and colonoscopy are recommended for subjects above 50 years of age for screening for colorectal cancer (CRC). AIM To evaluate the cost-effectiveness of FOBT, FS and colonoscopy on the basis of disease prevalence, compliance rate and cost of screening procedures in Asian countries. METHODS A hypothetical population of 100 000 persons aged 50 undergoes either FOBT annually, FS every 5 years or colonoscopy every 10 years until the age of 80 years. Patients with positive FOBT or polyp in FS are offered colonoscopy. Surveillance colonoscopy is repeated every 3 years. The treatment cost of CRC, including surgery and chemotherapy, was evaluated. A Markov model was used to compare the cost-effectiveness of different screening strategies. RESULTS Assuming a compliance rate of 90%, colonoscopy, FS and FOBT can reduce CRC incidence by 54.1%, 37.1% and 29.3% respectively. The incremental cost-effectiveness ratio (ICER) for FOBT (US$6222 per life-year saved) is lower than FS (US$8044 per life-year saved) and colonoscopy (US$7211 per life-year saved). When the compliance rate drops to 50% and 30%, FOBT still has the lowest ICER. CONCLUSION FOBT is cost-effective compared to FS or colonoscopy for CRC screening in average-risk individuals aged from 50 to 80 years.
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Abstract
Colorectal cancer (CRC) is the third most common cancer and the fifth leading cause of cancer-related mortality in China with an increasing trend, which is emphasizing the need for improvements in therapeutic options. The 5-year survival rate of surgery, the first-line treatment for CRC, is just about 50 percent. In recent years many patients with CRC have benefited from the combined treatment with surgery for CRC, which integrates chemotherapy, radiotherapy, concurrent chemoradiotherapy, biotherapy, traditional Chinese medicine, etc., especially patients at advanced stage. This paper highlighted current situation for combined treatment with surgery for CRC.
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