S-1 or gemcitabine adjuvant therapy in resected pancreatic cancer: a cost-effectiveness analysis based on the JASPAC-01 trial.

Purpose: This study aimed to investigate the cost-effectiveness of adjuvant treatments in resected pancreatic cancer.Methods: A Markov model was developed to mimic the disease process of postoperative pancreatic cancer, encompassing three health states (relapse-free survival, recurrent disease, and death). Health outcomes and utility scores were derived from the phase III trial and available literature. Cost data were calculated using standard fee data from the West China Hospital for 2017. One-way sensitivity analyses and probabilistic sensitivity analyses were developed to explore model uncertainty.Results: Treatment with S-1 was estimated to yield 1.61 quality-adjusted life-years (QALYs) at a cost of $25,696, whereas treatment with gemcitabine yielded 1.27 QALYs at a cost of $28,930. The incremental cost-effectiveness ratio of S-1 versus gemcitabine was $-9,490 per QALY. Based on the willingness-to-pay threshold of $25,841 per QALY, the net monetary benefit (NMB) was $15,786 for S-1 and $3,727 for gemcitabine, generating the incremental NMB of $12,059. A probabilistic sensitivity analysis revealed that the probabilities of S-1 and gemcitabine being cost-effective were 92% and 8%, respectively. Results were robust to changes in parameters.Conclusion: Adjuvant therapy using S-1 is a cost-effective alternative compared to gemcitabine in patients with postoperative pancreatic cancer from the Chinese societal perspective.

Cost minimization comparison of oral UFT/leucovorin versus 5-fluorouracil/leucovorin as adjuvant therapy for colorectal cancer in Taiwan.

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.

[Comparison of the Cost-Effectiveness of the SOX and COX Regimens in Patients with Unresectable Advanced and Recurrent Colorectal Cancer Using a Clinical Decision Analysis Approach].

Phase III clinical trials have comfirmed that the S-1 plus oxaliplatin(SOX)is inferior to the capecitabine plus oxaliplatin (COX)regimen in the treatment of metastatic colorectal cancer.On the basis of these findings, we compared, using a clinical decision analysis-based approach, the cost-effectiveness of the SOX and COX regimens.Herein, we simulated the expected effects and costs of the SOX and COX regimens using the markov model.Clinical data were obtained from Hong's 2012 report.The cost data comprised the costs for pharmacist labor, material, inspection, and treatment for adverse event, as well as the total cost of care at the advanced stage.The result showed that the expected cost of the SOX and COX regimen was 1,538,330 yen, and 1,429,596 yen, respectively, with an expected survival rate of 29.18 months, and 28.63 months, respectively.The incremental cost-effectiveness ratio of the SOX regimen was 197,698 yen/month; thus, the SOX regimen was found to be more cost-effective that the COX regimen.

Cost-effectiveness analysis of adjuvant chemotherapies in patients presenting with gastric cancer after D2 gastrectomy.

BACKGROUND: To analyze and compare the economic outcomes of adjuvant chemotherapy with capecitabine plus oxaliplatin (referred to as the XELOX strategy) and of S-1 (the S-1 strategy) for gastric cancer patients after D2 gastrectomy. METHODS: A Markov model was developed to simulate the lifetime disease course associated with stage II or III gastric cancer after D2 gastrectomy. The lifetime quality-adjusted life years (QALYs), associated costs, and incremental cost-effectiveness ratios (ICERs) were estimated. The clinical data were derived from the results of pilot studies. Direct costs were estimated from the perspective of the Chinese healthcare system, and the utility data were measured from end-point observations of Chinese patients. Sensitivity analyses were used to explore the impact of uncertainty on the model's outcomes. RESULTS: The combined adjuvant chemotherapy strategy with XELOX yielded the greatest increase in QALYs over the course of the disease (8.1 QALYs compared with 7.8 QALYs for the S-1 strategy and 6.2 for surgery alone). The incremental cost per QALY gained using the XELOX strategy was significantly lower than that for the S-1 strategy ($3,502 vs. $6,837, respectively). The results were sensitive to the costs of oxaliplatin and the hazard ratio of relapse-free survival. CONCLUSION: The observations reported herein suggest that adjuvant therapy with capecitabine plus oxaliplatin is a highly cost-effective strategy and more favorable treatment option than the S-1 strategy in patients with stage II or III gastric cancer who have undergone D2 gastrectomy.

Economic evaluation of first-line adjuvant chemotherapies for resectable gastric cancer patients in China.

BACKGROUND: First-line postoperative adjuvant chemotherapies with S-1 and capecitabine and oxaliplatin (XELOX) were first recommended for resectable gastric cancer patients in the 2010 and 2011 Chinese NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer; however, their economic impact in China is unknown. OBJECTIVE: The aim of this study was to compare the cost-effectiveness of adjuvant chemotherapy with XELOX, with S-1 and no treatment after a gastrectomy with extended (D2) lymph-node dissection among patients with stage II-IIIB gastric cancer. METHODS: A Markov model, based on data from two clinical phase III trials, was developed to analyse the cost-effectiveness of patients in the XELOX group, S-1 group and surgery only (SO) group. The costs were estimated from the perspective of Chinese healthcare system. The utilities were assumed on the basis of previously published reports. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated with a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. RESULTS: For the base case, XELOX had the lowest total cost ($44,568) and cost-effectiveness ratio ($7,360/QALY). The relative scenario analyses showed that SO was dominated by XELOX and the ICERs of S-1 was $58,843/QALY compared with XELOX. The one-way sensitivity analysis showed that the most influential parameter was the utility of disease-free survival. The probabilistic sensitivity analysis predicted a 75.8% likelihood that the ICER for XELOX would be less than $13,527 compared with S-1. When ICER was more than $38,000, the likelihood of cost-effectiveness achieved by S-1 group was greater than 50%. CONCLUSIONS: Our results suggest that for patients in China with resectable disease, first-line adjuvant chemotherapy with XELOX after a D2 gastrectomy is a best option comparing with S-1 and SO in view of our current study. In addition, S-1 might be a better choice, especially with a higher value of willingness-to-pay threshold.

Cost-effectiveness of adjuvant chemotherapy for curatively resected gastric cancer with S-1.

BACKGROUND: The effectiveness of specific regimens of adjuvant therapy for gastric cancer has not been verified by large clinical trials. Recently, several large trials attempted to verify the effectiveness of adjuvant therapy. The Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer in Japan, a randomized controlled trial of adjuvant S-1 therapy for resected gastric cancer, demonstrated significant improvement in overall and relapse-free survival, compared to surgery alone. To evaluate value for money of S-1 therapy, cost-effective analysis was carried out. METHODS: The analysis was carried out from a payer's perspective. As an economic measure, cost per quality-adjusted life-year (QALY) gained was estimated. Overall survival was estimated by the Kaplan-Meier method, up to 5-year observation. Beyond this period, it was simulated by the modified Boag model. Utility score is derived from interviews with sampled patients using a time trade-off method. Costs were estimated from trial data during observation, while in the period beyond observation they were estimated using simulation results. To explore uncertainty of the results, qualitative and stochastic sensitivity analyses were done. RESULTS: Adjuvant S-1 therapy gained 1.24 QALYs per patient and increased costs by $3,722 per patient for over lifetime (3% discount rate for both effect and costs). The incremental cost-effectiveness ratio (95% confidence intervals) for over lifetime was estimated to be $3,016 ($1,441, $8,840) per QALY. The sensitivity analyses showed the robustness of these results. CONCLUSION: Adjuvant S-1 therapy for curatively resected gastric cancer is likely cost-effective. This therapy can be accepted for wide use in Japan.

[A retrospective study of UFT and oral leucovorin plus PSK combination adjuvant chemotherapy in patients with stage III colon cancer].

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.

[Cost-effectiveness analysis of chemotherapy with GEM or S-1 for patients with non-resectable pancreatic cancer].

OBJECTIVE: To assess the cost-effectiveness of chemotherapy for patients with non-resectable pancreatic cancer, we compared two regimens containing either gemcitabine (GEM) or S-1. METHODS: We developed a decision tree that showed the clinical processes of non-resectable pancreatic cancer patients. We calculated the probabilities of endpoint and life months gained (LMG) based on previously reported articles. To estimate the costs, we analyzed medical records of 44 inpatients with non-resectable pancreatic cancer treated with GEM(n=34)or S-1(n=10). Sensitivity analysis was used to check the robustness of the results. RESULTS: In the GEM group and S-1 group, costs were 1,636,393 and 985,042 yen, and LMG was 6. 0 and 9. 0 months, respectively. Thus, the cost-effectiveness ratio(CER)was calculated to be 272,732 and 109,449 yen/LMG, respectively, and the incremental cost effectiveness ratio (ICER) was -217,117 yen/LMG. The sensitivity analysis showed that the result was definitely robust. CONCLUSION: Our findings suggest that the markedly cost-effective S-1 regimen could prolong LMG with less cost than the GEM regimen.

[A case of recurrent rectal cancer with multiple lung metastases successfully treated with S-1 and CPT-11 combination chemotherapy].

We report a case of recurrent rectal cancer with multiple lung metastases successfully treated with S-1 and CPT-11 combination chemotherapy. Rectal amputation was carried out on the rectal cancer patient, a 63-year-old man. CT scan revealed multiple lung metastases after 20 months of surgery. The patient was treated with S-1 and CPT-11 combination chemotherapy. S-1(100mg/body/day)was orally administered for 2 weeks followed by a 1-week interval, and CPT-11 (120 mg/body on day 1)was simultaneously administered. After completion of 8 courses, CT scan showed no lung metastases, and the patient was judged to have achieved a complete response (CR). The CR interval was maintained for twelve months until 20 courses of chemotherapy had been completed. This chemotherapy was expected to have a potent therapeutic efficacy for recurrent rectal cancer, considering the convenience, cost benefit and no severe adverse event.

Cost-effectiveness of adjuvant chemotherapy with uracil-tegafur for curatively resected stage III rectal cancer.

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.

The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer.

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.

Clinical and cost-effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer: systematic review and economic evaluation.

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.

A cost comparison of oral tegafur plus uracil/folinic acid and parenteral fluorouracil for colorectal cancer in Canada.

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.

[Pharmacoeconomic study of chemotherapy for gastric cancer: analysis of medical costs for oral fluoropyrimidine TS-1 and conventional i.v therapy].

To evaluate the economic impact of TS-1, an oral fluoropyrimidine, on the treatment of gastric cancer, the medical costs required for TS-1 treatment were compared with those for the conventional chemotherapy employed before the launch of TS-1 in patients with advanced and recurrent gastric cancer. The medical costs for 13 patients receiving TS-1 and 10 patients undergoing the conventional chemotherapy were extracted from the ordering system data, and the costs were compared using the fee schedule of the Japanese national health insurance. The monthly medical costs for the TS-1 group and conventional chemotherapy group were 327, 640 +/- 47,647 (mean +/- SE) yen and 852,874 +/- 62,412 yen, respectively. Medical costs appeared to have decreased because TS-1 is an oral preparation, permitting an easy transfer from inpatient treatment to ambulatory treatment, and because only small amounts of medication and blood transfusion were used for supportive care. Consequently, the medical costs for the TS-1 group were significantly lower than for the conventional chemotherapy group. Therefore, the administration of TS-1 leads to a reduction in medical costs.

A pharmacoeconomic comparison of UFT and 5-FU chemotherapy for colorectal cancer in South America.

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.

Advanced colorectal carcinoma: redefining the role of oral ftorafur.

The therapeutic performance, effect on quality of life and cost effectiveness of an orally administered medication in a home care setting were examined prospectively in a group of 61 patients presenting with advanced colorectal carcinoma. A regimen of daily ftorafur capsules (370 mg/m2) and leucovorin tablets (20 mg/m2) was offered to 35 symptomatic patients with poor performance status; the standard in-hospital i.v. protocol of 5-fluouracil and leucovorin was given to the remaining 26 patients. Follow-up and survival analysis indicated that there was no compromise in survival associated with home care and oral chemotherapy. There were statistically significant advantages in terms of reduced toxicity and improved Karnofsky performance status in this group. Home care was approximately 70% less expensive. A home treatment program based on oral ftorafur may be the most desirable option for all patients with advanced colorectal carcinoma.