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Aim: The objective of this study was to compare adverse event (AE) management costs for fruquintinib, regorafenib, trifluridine/tipiracil (T/T) and trifluridine/tipiracil+bevacizumab (T/T+bev) for patients with metastatic colorectal cancer (mCRC) previously treated with at least two prior lines of therapy from the US commercial and Medicare payer perspectives. Materials & methods: A cost-consequence model was developed to calculate the per-patient and per-patient-per-month (PPPM) AE costs using rates of grade 3/4 AEs with incidence ≥5% in clinical trials, event-specific management costs and duration treatment. Anchored comparisons of AE costs were calculated using a difference-in-differences approach with best supportive care (BSC) as a common reference. AE rates and treatment duration were obtained from clinical trials: FRESCO and FRESCO-2 (fruquintinib), RECOURSE (T/T), CORRECT (regorafenib) and SUNLIGHT (T/T, T/T+bev). AE management costs for the commercial and Medicare perspectives were obtained from publicly available sources. Results: From the commercial perspective, the AE costs (presented as per-patient, PPPM) were: $4015, $1091 for fruquintinib (FRESCO); $4253, $1390 for fruquintinib (FRESCO-2); $17,110, $11,104 for T/T (RECOURSE); $9851, $4691 for T/T (SUNLIGHT); $8199, $4823 for regorafenib; and $11,620, $2324 for T/T+bev. These results were consistent in anchored comparisons: the difference-in-difference for fruquintinib based on FRESCO was -$1929 versus regorafenib and -$11,427 versus T/T; for fruquintinib based on FRESCO-2 was -$2257 versus regorafenib and -$11,756 versus T/T. Across all analyses, results were consistent from the Medicare perspective. Conclusion: Fruquintinib was associated with lower AE management costs compared with regorafenib, T/T and T/T+bev for patients with previously treated mCRC. This evidence has direct implications for treatment, formulary and pathways decision-making in this patient population.

Aims: Fruquintinib is a selective small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3 recently approved in the United States (US) for the treatment of adult patients with metastatic colorectal cancer (CRC) who have previously been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type and medically appropriate, anti-epidermal growth factor receptor therapy. This study aimed to estimate the 5-year budget impact of fruquintinib from a US payer perspective (commercial and Medicare)., Materials and Methods: A budget impact model was developed to compare two scenarios: a reference scenario in which patients received regorafenib, trifluridine/tipiracil, or trifluridine/tipiracil with bevacizumab and an alternative scenario in which patients received reference scenario treatments or fruquintinib. Market shares were evenly divided across available options. A 5-year time horizon and a hypothetical health plan of 1 million members was assumed. The model included epidemiological inputs to estimate the eligible population; clinical inputs for treatment duration, progression-free survival, overall survival, and adverse event (AE) frequency; and cost inputs for treatment, AEs, disease management, subsequent therapy, and terminal care costs. Budget impact was reported as total, per member per year (PMPY), and per member per month (PMPM)., Results: The model estimated an eligible population of 194 patients (39 per year) over 5 years. In the base case, the estimated 5-year budget impact of fruquintinib was $4,077,073 ($0.82 PMPY and 0.07 PMPM) for a commercial health plan. During the first year, the estimated budget impact was $627,570 ($0.63 PMPY and 0.05 PMPM). Results were robust across sensitivity analyses. PMPM costs from the Medicare perspective were greater than the base-case (commercial) ($0.17 vs. $0.07) due to higher incidence of CRC in that population., Conclusions: Fruquintinib is associated with a low budget impact for payers based on proposed thresholds in the US.

Purpose: Dipeptidylpeptidase-4 (DPP-4) inhibitors, including linagliptin, alogliptin, saxagliptin, sitagliptin, and vildagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM) patients in China. This study assessed the economic outcomes of different DPP-4 inhibitors in patients with T2DM inadequately controlled with metformin in the Chinese context., Materials and Methods: In this study, the validated Chinese Outcomes Model for T2DM (COMT) was conducted to project economic outcomes from the perspective of Chinese healthcare service providers. Efficacy and safety, medical expenditure, and utility data were derived from the literature, which were assigned to model variables. The primary outputs of the model included the lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analysis was conducted to assess the potential uncertainties of parameters., Results: Of the five competing strategies, alogliptin 25 mg strategy yielded the most significant health outcome, which associated with improvements in discounted QALY of 0.007, 0.014, 0.011, and 0.022 versus linagliptin 5 mg, saxagliptin 5 mg, sitagliptin 100 mg and vildagliptin50 mg, respectively. The sitagliptin 100 mg strategy was the cheapest option. The ICER of alogliptin 25 mg against sitagliptin 100 mg strategy was $6,952 per additional QALY gained, and the rest of the strategies were dominated or extended dominated. The most influential parameters were the cost of DPP-4 inhibitors and their treatment efficacy., Conclusions: These results suggested that alogliptin was a preferred treatment option compared with other DPP-4 inhibitors for Chinese patients whose T2DM are inadequately controlled on metformin monotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lin, Cai, Chen, Liu, Li and Zheng.)

Objectives: The combination of pegylated-interferon and ribavirin (PegIFN+RBV) is currently the gold standard in treating chronic hepatitis C virus (HCV) patients in Malaysia and is reimbursed by the Malaysian authorities. This analysis evaluated the cost-effectiveness (CE) of the ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin (OBT/PTV/r+DSB±RBV) regimen as compared with the PegIFN+RBV or no treatment in chronic HCV Genotype 1 (GT1) treatment-naïve and treatment-experienced cirrhotic and noncirrhotic patients in Malaysia., Methods: A Markov model based on previously published CE models of HCV was adapted for the Malaysian public healthcare payer perspective, based on good modeling practices. Treatment attributes included efficacy, regimen duration, and EQ-5D treatment-related health utility. Transitional probabilities and health state health utilities were derived from previous studies. Costs were derived from Malaysian data sources. Costs and outcomes were discounted at 3.0% per year. Deterministic and probabilistic sensitivity analyses were performed to evaluate the impact of uncertainties around key variables., Results: Based on the analysis, patients treated with the OBT/PTV/r+DSB±RBV showed less frequent progression to compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths when compared with standard care (ie, PegIFN+RBV or no treatment). At a price of MYR 1846/day, the OBT/PTV/r+DSB±RBV regimen is cost-effective over PegIFN+RBV and yields better outcomes in terms of life-years (LYs) gained and quality-adjusted life-years (QALYs) at a higher cost, which is still well below the implied willingness to pay threshold of MYR 384 503/QALY., Conclusion: The OBT/PTV/r+DSB±RBV regimen is cost-effective for treatment naïve, treatment experienced, cirrhotic, and noncirrhotic GT1 chronic HCV patients in Malaysia., (Copyright © 2019 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Trifluridine/tipiracil (TAS102), a novel oral cytotoxic chemotherapy, significantly improved overall survival compared with placebo in heavily pretreated advanced gastric cancer. This study aimed to evaluate the cost-effectiveness of TAS102 in the third-line or later treatment for this population from the US payer perspective., Methods: A Markov model was developed to simulate advanced gastric cancer, including three health states: progression-free survival (PFS), progressive disease (PD) and death. Model inputs were derived from a randomised, double-blind, placebo-controlled, phase 3 trial (TAGS trial, NCT02500043). Utilities were extracted from public resources. Costs were calculated from an American payer perspective. Sensitivity analyses were conducted to explore the impact of uncertainty., Results: From the US payer perspective, treatment with TAS102 for patients with heavily pretreated advanced gastric cancer was estimated to increase costs by $59,180 compared with the placebo, with a gain of 0.06 quality-adjusted life years (QALYs) for an incremental cost-effectiveness ratio (ICER) of $986,333 per QALY. The costs for progression-free survival of TAS102 group had the greatest impact on the ICERs, as well as the cost of TAS102., Conclusion: Trifluridine/tipiracil (TAS102) is not a cost-effective choice for patients with heavily pretreated metastatic gastric cancer from an American payer perspective.

Aim: Oral uracil-tegafur/leucovorin (UFT/LV) and intravenous 5-fluorouracil (FU)/LV are common adjuvant therapies for Stages II and III colorectal cancer. This study aims to determine the most cost-effective treatment alternative between UFT/LV and 5-FU/LV in Stages II and III colorectal cancer from Taiwan's National Health Insurance perspective., Patients & Methods: The costs were referenced directly from the National Health Insurance reimbursement price. Chemotherapy regimen considered for the cost analysis calculation was adapted from NSABP-C-06 study, and, a time saving calculation was also included. In addition, we compare the treatment outcome., Result: A total cost saving of US$3620.80-$3709.16 per patient per treatment was achieved with the UFT/LV treatment. UFT/LV provides the comparable outcome to 5-FU/LV., Conclusion: UFT/LV was the more cost-effective treatment as adjuvant chemotherapy.

Objectives: To estimate clinical outcomes and cost-effectiveness of ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin (OMB/PTV/r + DSV ± RBV) compared with treatment regimens including pegylated interferon (PegIFN) for patients with chronic genotype 1 hepatitis C virus (HCV) infection., Methods: An Excel spreadsheet Markov model tracking progression through stages of liver disease was developed. Costs and patient utilities for liver disease stages were taken from published studies. Rates of disease progression were based on studies of untreated HCV infection and long-term follow-up of those achieving sustained virologic response (SVR) after drug treatment. Impact of OMB/PTV/r + DSV ± RBV and other drug regimens on progression was estimated through SVR rates from clinical trials. Analyses were performed for treatment-naive and treatment-experienced patients. Impact of alternative scenarios and input parameter uncertainty on the results were tested., Results: For genotype 1 treatment-naive HCV patients, for OMB/PTV/r + DSV ± RBV, PegIFN + ribavirin (PegIFN/RBV), sofosbuvir + PegIFN/RBV, telaprevir + PegIFN/RBV, boceprevir + PegIFN/RBV, lifetime risk of decompensated liver disease was 5.6%, 18.9%, 7.4%, 11.7%, and 14.9%; hepatocellular carcinoma was 5.4%, 9.2%, 5.7%, 7.0%, and 7.4%; and death from liver disease was 8.7%, 22.2%, 10.4%, 14.8%, and 17.6%, respectively. Estimates of the cost-effectiveness of OMB/PTV/r + DSV ± RBV for treatment-naive and treatment-experienced patients indicated that it dominated all other regimens except PegIFN/RBV. Compared with PegIFN/RBV, the incremental cost-effectiveness ratios were £13,864 and £10,258 per quality-adjusted life-year (QALY) for treatment-naive and treatment-experienced patients, respectively. The results were similar for alternative scenarios and uncertainty analyses., Limitations: A mixed-treatment comparison for SVR rates for the different treatment regimens was not feasible, because many regimens did not have comparator arms; instead SVR rates were based on those from recent trials., Conclusions: OMB/PTV/r + DSV ± RBV is a cost-effective oral treatment regimen for chronic genotype 1 HCV infection compared with standard treatment regimens and is estimated to reduce the lifetime risks of advanced liver disease.

Introduction: New treatments for chronic hepatitis C virus (HCV) are highly effective in patients coinfected with human immunodeficiency virus (HIV). This study estimated the cost-effectiveness of treatments for genotype 1 (GT1) HCV in HIV-coinfected patients., Methods: A Markov model based on HCV natural history was used. The base-case analysis included both treatment-naïve and -experienced patients. Alternatives were ombitasvir/paritaprevir/ritonavir, dasabuvir with or without ribavirin (3D ± R) for 12 or 24 weeks, sofosbuvir plus peginterferon and R (SOF + PR) for 12 weeks, SOF + R for 24 weeks, and no treatment (NT). A subgroup analysis restricted to treatment-naïve, non-cirrhotic patients compared 3D ± R for 12 weeks to SOF plus ledipasvir (LDV) for 12 weeks and NT. Transition probabilities, utilities, and costs were obtained from the published literature. Outcomes were measured over a lifetime horizon and included rates of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver-related death, total costs, life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER)., Results: In the base-case, SOF + R was dominated by both SOF + PR and 3D ± R. Compared to SOF + PR, 3D ± R had an ICER of $45,581. The lifetime rates of liver morbidity and mortality were lower among those treated with 3D ± R compared to SOF + PR, SOF + R, or NT. In the subgroup analysis, 3D ± R was cost-effective compared to NT at a threshold of $50,000 per QALY (ICER $27,496). SOF/LDV had an ICER of $104,489 per QALY gained compared to 3D ± R., Conclusion: In the GT1 HCV population coinfected with HIV, 3D ± R was cost-effective compared to NT, SOF + R, and SOF + PR. In the treatment-naïve sub-population, 3D ± R was cost-effective compared to NT and SOF/LDV.

Objective: This study compared the cost-effectiveness of direct-acting antiviral therapies currently recommended for treating genotypes (GT) 1 and 4 chronic hepatitis C (CHC) patients in the US., Methods: A cost-effectiveness analysis of treatments for CHC from a US payer's perspective over a lifelong time horizon was performed. A Markov model based on the natural history of CHC was used for a population that included treatment-naïve and -experienced patients. Treatment alternatives considered for GT1 included ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± R), sofosbuvir + ledipasvir (SOF/LDV), sofosbuvir + simeprevir (SOF + SMV), simeprevir + pegylated interferon/ribavirin (SMV + PR) and no treatment (NT). For GT4 treatments, ombitasvir/paritaprevir/ritonavir + ribavirin (2D + R), SOF/LDV and NT were compared. Transition probabilities, utilities and costs were obtained from published literature. Outcomes included rates of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC) and liver-related death (LrD), total costs, life-years and quality-adjusted life-years (QALYs). Costs and QALYs were used to calculate incremental cost-effectiveness ratios., Results: In GT1 patients, 3D ± R and SOF-containing regimens have similar long-term outcomes; 3D ± R had the lowest lifetime risks of all liver disease outcomes: CC = 30.2%, DCC = 5.0 %, HCC = 6.8%, LT = 1.9% and LrD = 9.2%. In GT1 patients, 3D ± R had the lowest cost and the highest QALYs. As a result, 3D ± R dominated these treatment options. In GT4 patients, 2D + R had lower rates of liver morbidity and mortality, lower cost and more QALYs than SOF/LDV and NT., Limitations: While the results are based on input values, which were obtained from a variety of heterogeneous sources-including clinical trials, the findings were robust across a plausible range of input values, as demonstrated in probabilistic sensitivity analyses., Conclusions: Among currently recommended treatments for GT1 and GT4 in the US, 3D ± R (for GT1) and 2D + R (for GT4) have a favorable cost-effectiveness profile.

Background: Interferon-free hepatitis C treatment regimens are effective but very costly. The cost-effectiveness, budget, and public health impacts of current Medicaid treatment policies restricting treatment to patients with advanced disease remain unknown., Objectives: To evaluate the cost-effectiveness of current Medicaid policies restricting hepatitis C treatment to patients with advanced disease compared with a strategy providing unrestricted access to hepatitis C treatment, assess the budget and public health impact of each strategy, and estimate the feasibility and long-term effects of increased access to treatment for patients with hepatitis C., Methods: Using a Markov model, we compared two strategies for 45- to 55-year-old Medicaid beneficiaries: 1) Current Practice-only advanced disease is treated before Medicare eligibility and 2) Full Access-both early-stage and advanced disease are treated before Medicare eligibility. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die each year. Morbidity was reduced after successful treatment. We calculated the incremental cost-effectiveness ratio and compared the costs and public health effects of each strategy from the perspective of Medicare alone as well as the Centers for Medicare & Medicaid Services perspective. We varied model inputs in one-way and probabilistic sensitivity analyses., Results: Full Access was less costly and more effective than Current Practice for all cohorts and perspectives, with differences in cost ranging from $5,369 to $11,960 and in effectiveness from 0.82 to 3.01 quality-adjusted life-years. In a probabilistic sensitivity analysis, Full Access was cost saving in 93% of model iterations. Compared with Current Practice, Full Access averted 5,994 hepatocellular carcinoma cases and 121 liver transplants per 100,000 patients., Conclusions: Current Medicaid policies restricting hepatitis C treatment to patients with advanced disease are more costly and less effective than unrestricted, full-access strategies. Collaboration between state and federal payers may be needed to realize the full public health impact of recent innovations in hepatitis C treatment., (Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background & Aims: Orthotopic liver transplant patients with recurrent hepatitis C (HCV) historically have had limited treatment options. Ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin (3D+R) was approved by the FDA in December 2014 for liver transplant recipients with recurrent genotype 1 HCV, in whom it is effective and well-tolerated., Methods: Using a two-phase Markov model, we analysed the cost-effectiveness of 3D+R in liver transplant recipients, the only HCV treatment with FDA approval in this population. As a sensitivity analysis, we also considered the cost-effectiveness of pegylated interferon plus ribavirin, the only other therapy with data from Phase III trials in this population. Patients were given one of three options: 3D+R for 24 weeks, pegylated interferon and ribavirin for 48 weeks (PR48) or no treatment (NT). Patients were then followed through subsequent disease progression until death. Outcome measures analysed were: lifetime risks of liver morbidity and mortality, treatment costs, non-treatment medical expenditures, and quality-adjusted life years., Results: Treatment with 3D+R was associated with a significantly lower lifetime risk of liver-related morbidity and mortality than treatment with PR48 or NT. 3D+R also was associated with a higher gain in quality-adjusted life years (11.3 compared to 8.25 with NT) and lower discounted overall costs ($423,585 compared to $724,757 with NT)., Conclusions: The use of 3D+R for liver transplant recipients with recurrent HCV is an outcome-improving and cost-effective regimen for this population with limited treatment options and large unmet need., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The standard care of treatment of interferon plus ribavirin (plus protease inhibitor for genotype 1) are effective in 50 % to 70 % of patients with CHC. Several new treatments including Harvoni, Olysio + Sovaldi, Viekira Pak, Sofosbuvir-based regimens characterized with potent inhibitors have been approved by the Food and Drug Administration (FDA) providing more options for CHC patients. Trials have shown that the new treatments increased the rate to 80% to 95%, though with a substantial increase in cost. In particular, current market pricing of a 12-week course of sofosbuvir is approximately US$84,000. We determine the cost-effectiveness of new treatments in comparison with the standard care of treatments., Methods: A Markov simulation model of CHC disease progression is used to evaluate the cost-effectiveness of different treatment strategies based on genotype. The model calculates the expected lifetime medical costs and quality adjusted life years (QALYs) of hypothetical cohorts of identical patients receiving certain treatments. For genotype 1, we compare: (1) peginterferon + ribavirin + telaprevir for 12 weeks, followed by 12 or 24 weeks treatment of peginterferon + ribavirin dependent on HCV RNA level at week 12; (2) Harvoni treatment, 12 weeks; (3) Olysio + Sovaldi, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (4) Viekira Pak + ribavirin, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (5) sofosbuvir + peginterferon + ribavirin, 12 weeks for patients with or without cirrhosis. For genotypes 2 and 3, treatment strategies include: (1) peginterferon + ribavirin, 24 weeks for treatment-naïve patients; (2) sofosbuvir + ribavirin, 12 weeks for patients with genotype 2, 24 weeks for genotype 3; (3) peginterferon + ribavirin as initial treatment, 24 weeks for patients with genotype 2/3, follow-up treatment with sofosbuvir + ribavirin for 12/16 weeks are performed on non-responders and relapsers., Results: Viekira Pak is cost-effective for genotype 1 patients without cirrhosis, whereas Harvoni is cost-effective for genotype 1 patients with cirrhosis. Sofosbuvir-based treatments for genotype 1 in general are not cost-effective due to its substantial high costs. Two-phase treatments with 12-week and 16-week follow-ups are cost-effective for genotype 3 patients and for genotype 2 patients with cirrhosis. The results were shown to be robust over a broad range of parameter values through sensitivity analysis., Conclusions: For genotype 1, sofosbuvir-based treatments are not cost-effective compared to Viekira Pak and Harvoni, although a 30% reduction in sofosbuvir price would change this result. Sofosbuvir + ribavirin are cost-effective as second-phase treatments following peginterferon + ribavirin initial treatment for genotypes 2 and 3. However, there is limited data on sofosbuvir-involved treatment, and the results obtained in this study must be interpreted within the model assumptions.

Objective: To perform a retrospective analysis of UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer in order to evaluate both treatment efficacy and toxicity., Subjects: Between 2003 and 2009, 273 stage III colon cancer patients underwent surgery in our institute, and we studied 156 of them., Results: Patients' median age was 72 years old; 87 men and 69 women. Of all patients, 119 had stage IIIa and 37 had stage IIIb. The 3-year disease, free survival rates for stage III, stage IIIa and stage IIIb patients were 73. 9%and 80. 6%and 51. 4%, respectively, and the 3-year overall survival rates for stage III was 97. 6%. With regard to toxicity, liver function disorder was observed in 9. 6%of the patients as the most frequent adverse event, but there was no grade 3 or 4 toxicity., Conclusion: UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer showed a good response especially for stage III a.

Recently, the National Surgical Adjuvant Study of Colorectal Cancer in Japan, a randomised controlled trial of oral uracil-tegafur (UFT) adjuvant therapy for stage III rectal cancer, showed remarkable survival gains, compared with surgery alone. To evaluate value for money of adjuvant UFT therapy, cost-effective analysis was carried out. Cost-effectiveness analysis of adjuvant UFT therapy was carried out from a payer's perspective, compared with surgery alone. Overall survival and relapse-free survival were estimated by Kaplan-Meier method, up to 5.6 years from randomisation. Costs were estimated from trial data during observation. Quality-adjusted life-years (QALYs) were calculated using utility score from literature. Beyond observation period, they were simulated by the Boag model combined with the competing risk model. For 5.6-year observation, 10-year follow-up and over lifetime, adjuvant UFT therapy gained 0.50, 0.96 and 2.28 QALYs, and reduced costs by $2457, $1771 and $1843 per person compared with surgery alone, respectively (3% discount rate for both effect and costs). Cost-effectiveness acceptability and net monetary benefit analyses showed the robustness of these results. Economic evaluation of adjuvant UFT therapy showed that this therapy is cost saving and can be considered as a cost-effective treatment universally accepted for wide use in Japan.

Two oral fluoropyrimidine therapies have been introduced for metastatic colorectal cancer. One is a 5-fluorouracil pro-drug, capecitabine; the other is a combination of tegafur and uracil administered together with leucovorin. The purpose of this study was to compare the clinical effectiveness and cost-effectiveness of these oral therapies against standard intravenous 5-fluorouracil regimens. A systematic literature review was conducted to assess the clinical effectiveness of the therapies and costs were calculated from the UK National Health Service perspective for drug acquisition, drug administration, and the treatment of adverse events. A cost-minimisation analysis was used; this assumes that the treatments are of equal efficacy, although direct randomised controlled trial (RCT) comparisons of the oral therapies with infusional 5-fluorouracil schedules were not available. The cost-minimisation analysis showed that treatment costs for a 12-week course of capecitabine (Pounds 2132) and tegafur with uracil (Pounds 3385) were lower than costs for the intravenous Mayo regimen (Pounds 3593) and infusional regimens on the de Gramont (Pounds 6255) and Modified de Gramont (Pounds 3485) schedules over the same treatment period. Oral therapies result in lower costs to the health service than intravenous therapies. Further research is needed to determine the relative clinical effectiveness of oral therapies vs infusional regimens.

Objectives: To evaluate the clinical and cost-effectiveness of capecitabine and tegafur with uracil (UFT/LV) as first-line treatments for patients with metastatic colorectal cancer, as compared with 5-fluorouracil/folinic acid (5-FU/FA) regimens., Data Sources: Electronic databases, reference lists of relevant articles and sponsor submissions were also consulted., Review Methods: Systematic searches, selection against criteria and quality assessment were performed to obtain data from relevant studies. Costs were estimated through resource-use data taken from the published trials and the unpublished sponsor submissions. Unit costs were taken from published sources, where available. An economic evaluation was undertaken to compare the cost-effectiveness of capecitabine and UFT/LV with three intravenous 5-FU/LV regimens widely used in the UK: the Mayo, the modified de Gramont regimen and the inpatient de Gramont regimens., Results: The evidence suggests that treatment with capecitabine improves overall response rates and has an improved adverse effect profile in comparison with 5-FU/LV treatment with the Mayo regimen, with the exception of hand-foot syndrome. Time to disease progression or death after treatment with UFT/LV in one study appears to be shorter than after treatment with 5-FU/LV with the Mayo regimen, although it also had an improved adverse effect profile. Neither capecitabine nor UFT/LV appeared to improve health-related quality of life. Little information on patient preference was available for UFT/LV, but there was indicated a strong preference for this over 5-FU/LV. The total cost of capecitabine and UFT/LV treatments were estimated at 2111 pounds and 3375 pounds, respectively, compared with the total treatment cost for the Mayo regimen of 3579 pounds. Cost estimates were also presented for the modified de Gramont and inpatient de Gramont regimens. These were 3684 pounds and 6155 pounds, respectively. No survival advantage was shown in the RCTs of the oral drugs against the Mayo regimen. Cost savings of capecitabine and UFT/LV over the Mayo regimen were estimated to be 1461 pounds and 209 pounds, respectively. Drug acquisition costs were higher for the oral therapies than for the Mayo regimen, but were offset by lower administration costs. Adverse event treatment costs were similar across the three regimens. It was inferred that there was no survival difference between the oral drugs and the de Gramont regimens. Cost savings of capecitabine and UFT/LV over the modified de Gramont regimen were estimated to be 1353 pounds and 101 pounds, respectively, and over the inpatient de Gramont regimen were estimated to be 4123 pounds and 2870 pounds, respectively., Conclusions: The results show that there are cost savings associated with the use of oral therapies. No survival difference has been proven between the oral drugs and the Mayo regimen. In addition, no evidence of a survival difference between the Mayo regimen and the de Gramont regimens has been identified. However, improved progression-free survival and an improved adverse event profile have been shown for the de Gramont regimen over the Mayo regimen. Further research is recommended into the following areas: quality of life data should be included in trials of colorectal cancer treatments; the place of effective oral treatments in the treatment of colorectal cancer, the safety mechanisms needed to ensure compliance and the monitoring of adverse effects; the optimum duration of treatment; the measurement of patient preference; and a phase III comparative trial of capecitabine and UFT/LV versus modified de Gramont treatment to determine whether there was any survival advantage and to collate the necessary economic data.

Background: Two randomised, controlled trials (n = 1396) comparing (i) intravenous fluorouracil (FU) plus oral folinic acid (leucovorin) and (ii) oral tegafur plus uracil (UFT) plus folinic acid for the treatment of metastatic colorectal carcinoma found both regimens to have equivalent efficacy in terms of survival, tumour response and time to disease progression. The UFT/folinic acid regimen was associated with a better toxicity profile than FU/folinic acid., Objective: To determine the comparative frequencies and costs of healthcare resources utilised in the treatment of patients with these two regimens from a hospital and government perspective., Design: A cost-minimisation analysis of a subgroup of patients from the trials (n = 154) was conducted. Costs considered included those for hospital admissions, outpatient clinics, laboratories, imaging modalities, other diagnostic procedures, physician resources, other health professionals, other procedures such as surgery and transfusion, and concomitant medications. The cost of study medications was not included in the analysis. The endpoint was a total average cost per patient per treatment and per cycle., Results: Patients on the oral UFT regimen had fewer outpatient clinic visits and used fewer laboratory resources than patients treated with FU. However, those on the oral regimen had more days of hospitalisation than the patients treated with the intravenous regimen. Patients treated with UFT used 21% less concomitant medication; however, in both groups these medications accounted for a similar percentage compared with the total costs of the treatment. Physicians' fees were similar for both groups but patients treated with UFT were seen more often by an attending physician. Patients on the UFT regimen visited outpatient oncology clinics less often and this was reflected by a maximum 826 Canadian dollars (Canadian dollars; 1996 values) total cost savings per patient per cycle and 3221 Canadian dollars per patient per treatment. An efficiency analysis showed that the use of the UFT/folinic acid regimen saved 4.5 hours per patient per month in the chemotherapy treatment unit compared with the FU regimen., Conclusions: In regard to the two therapeutic approaches, the cost of treatment per patient and per cycle using oral UFT/folinic acid was less than that using intravenous FU/folinic acid.

GW776C85 is a new drug that has been shown to be an effective inactivator of dihydropyrimidine dehydrogenase (DPD). Preclinical studies demonstrated that administration of GW776C85 with 5-fluorouracil (5-FU) resulted in several desirable pharmacologic effects. Initial clinical data on 5-FU combined with GW776C85 suggest potentially increased antitumor activity in at least some malignancies with tolerable toxicity, as well as several distinct economic and quality-of-life advantages including the following: (1) The possibility of administering 5-FU as an oral drug due to excellent bioavailability of 5-FU following inactivation of DPD; (2) a cost-effective alternative to continuous or protracted infusion of 5-FU without the need for hospitalization or surgical placement of an intravenous access and availability of an ambulatory pump; and (3) potential for less interpatient variation of 5-FU toxicity (e.g., in host tissues, such as bone marrow and gastrointestinal mucosa cells) due to inactivation of DPD in essentially all patients treated, permitting better 5-FU dosing guidelines. Finally, because tumors may theoretically become resistant to 5-FU by increased levels of DPD, the use of GW776C85 to inactivate DPD may provide a potential means by which tumor resistance can be reversed.

The escalating role played by managed care organizations in the health-care system is reflected in the increased demand for cost-effectiveness analyses (CEAs) to assess the balance between economic impact and clinical efficacy. For example, the high incidence and costs associated with colorectal cancer in Latin America calls for a comprehensive economic evaluation to ensure appropriate allocation of limited health-care funds. In addition, the current call for a "societal" perspective of such analyses indicates the need for increased consideration of the concerns of both patient and health-care provider. The introduction of oral tegafur and uracil (UFT) provided the opportunity to evaluate the pharmacoeconomic advantage of the new agent compared with the standard fluorouracil (5-FU). Results of this study indicated an economic advantage for oral UFT vs a 5-FU-based regimen in the treatment of colorectal cancer in Brazil and Argentina. It was further noted that the mild toxicity profile of UFT reduced both the number of clinic visits and the need for venipuncture procedures. Noting that oral UFT may have a positive impact on quality of life in addition to its estimated economic benefit, it was concluded that prospective economic research and quality-of-life evaluations are needed to fully assess the pharmacoeconomic impact of oral UFT.