Abstract
Background: EOX (epirubicin, oxaliplatin, Xeloda; capecitabine) and FOLFOX4 (5-fluorouracil (5-FU), leucovorin, oxaliplatin) are the common chemotherapy regimens used in the treatment of advanced gastric cancer (aGC) in Hong Kong. This study aimed to compare the costs of these therapies for aGC patients from both the healthcare and societal perspectives. It should be noted that, while FOLFOX4 is routinely administered in an outpatient setting in North America and Europe, inpatient setting is adopted in Hong Kong instead, incurring hospitalization cost as a result.
Methods: Fifty-eight patients were identified from the electronic records in two public tertiary hospitals, with 45 and 13 receiving EOX and FOLFOX4 regimens, respectively. Healthcare cost was direct medical costs including drugs, clinic follow-up, hospitalization, diagnostic laboratories, and radiographs. Societal cost refers to indirect costs such as patient time and travel costs. Cost items were further classified as “expected” or “unexpected”. All cost data was expressed in US dollars.
Results: Patients in the EOX and FOLFOX4 arm received an average of 5.3 and 7.8 cycles of treatment, respectively. The capecitabine-based regimen group had a higher expected medication cost per cycle when compared to the 5-FU-based treatment group (US$290.3 vs US$66.9, p < .001), but lower expected hospitalization costs (US$76.9 vs US$1,269.2, p < .001). The total healthcare cost and total societal cost per patient was reduced by 67.2% (US$5,691.9 vs US$17,357.4, p < .001) and 25.3% (US$3,090.5 vs US$4,135.1, p = .001), respectively, in the capecitabine-based regimen group. Sensitivity analyses based on full cycle regimen costs and net capecitabine or 5-FU/leucovorin costs still showed EOX to be less costly than FOLFOX4.
Conclusion: The capecitabine-based regimen, EOX, was found to generate significant cost saving from both the healthcare and societal perspectives in regions in which FOLFOX4 is given in an inpatient setting.
Background
Xeloda, capecitabine-based chemotherapy regimen, has been shown to be more cost-effective than 5-fluorouracil (5-FU), considering they have equivalent clinical efficacy in gastric cancer treatmentCitation1,Citation2. The total cost for the 5-FU-based regimen was higher for the healthcare provider and society as a wholeCitation1. Gastric cancer ranks fourth in cancer-related cause of death in the Hong Kong populationCitation3. 5-FU has known anti-tumor activity, and has been used successfully in advanced gastric cancer (aGC) with cisplatin (FP), as well as with oxaliplatin ± epirubicin (FOLFOX4, EOF)Citation4,Citation5,Citation6. When substituted with capecitabine, the capecitabine + cisplatin (XP) and epirubicin cisplatin + capecitabine (EOX) regimens have been demonstrated to be non-inferior in terms of progression-free survival when compared with FP and EOF, respectivelyCitation7. In an economics evaluation done by the manufacturer for NICE submission on the use of capecitabine for treatment of aGC, the use of XP regimen allowed a cost reduction, while eliminating possible complications related to intravenous therapyCitation8. Moreover, FOLFOX4, one of the common 5-FU-based regimens used locally, has been demonstrated to produce a median overall survival of 10 months in advanced/metastatic gastric cancer patients, an effect similar to that of EOXCitation9. Xeloda, capecitabine, was recently extended by the Hong Kong Hospital Authority as subsidized therapy for the treatment of colorectal cancerCitation10. Currently, there is no local-regional data suggesting a similar economic impact with a capecitabine-based regimen for gastric cancer when compared with 5-FU-based regimens. In fact, the current study is one of the few done in Asia to examine this question. It is worthwhile to see if capecitabine-based therapy for gastric cancer is a cost-effective alternative. This study assumed equal clinical effectiveness between the EOX and FOLFOX4 regimens. The study was designed to ensure comparability of the selected samples of treated patients and to compare the costs of treatment of the two chemotherapy regimen groups. This study aimed to compare the costs of these therapies for aGC patients from both the healthcare and societal perspectives. One point to note is that, while FOLFOX4 is routinely administered in North America and Europe in an outpatient setting, central venous catheters and out-patient ambulatory pumps are not used in Hong Kong. Instead, FOLFOX4 is administered in an inpatient setting. Therefore, the planned hospitalization for each cycle of FOLFOX4 administration is expected to be one of the major cost factors accounting for the cost difference between FOLFOX4 and EOX therapies in Hong Kong. The cost for FOLFOX4 administration would actually be substantially lower in North America and Europe.
Methods
Study design
This study was a retrospective study comparing the cost of EOX and FOLFOX4 regimen in the treatment of advanced gastric cancer (aGC). Patients with aGC were identified from medical records of the oncology department at Princess Margaret Hospital (PMH, 1,500 beds) and Pamela Youde Nethersole Eastern Hospital (PYNEH, 1,800 beds), which are two of the largest general public hospitals in Hong Kong. Information related to the use of hospital resources by each patient, including outpatient visits, inpatient admissions, laboratory tests, and procedures, as well as medications, were collected up to 1 month after the last cycle of therapy. Cost data was analyzed from the healthcare provider and societal perspectives. Under each perspective, costs were further divided into two categories, expected and unexpected. Expected costs were defined as costs directly incurred for chemotherapy administration, such as costs for chemotherapies, pre-medications, and fluids for infusion, as well as associated laboratory tests, hospital bed-days, and outpatient follow-up visits. Unexpected costs were described as costs unrelated to the actual chemotherapy treatment, and costs due to adverse events, disease progression, or toxicity management. The study protocol has obtained the Clinical Research Ethics Committee (CREC) approval from both the Kowloon West Cluster (PMH) and the Hong Kong East Cluster (PYNEH).
Patient population
Patients who were 18 years of age and older with aGC were eligible for this study. Patients were selected according to reverse chronological order, starting from the most recent cases. A target sample size was pre-defined to be 60 originally, with 30 patients in each arm. They were included between August 2007 and April 2012. The latest start date of chemotherapy was February 2012.
Treatment schedules
The EOX regimen followed the chemotherapy protocol issued by the National Health Service in the UKCitation11. It consisted of an intravenous bolus injection of epirubicin 50 mg/m2 and an intravenous infusion of oxaliplatin 130 mg/m2 over 2 h on day 1 of every 3 week cycle, together with oral capecitabine tablets 625 mg/m2 twice daily for 6 months. As for the FOLFOX4 regimen, it consisted of an intravenous infusion of oxaliplatin 85 mg/m2 over 2 h on day 1, and an intravenous infusion of folinic acid (leucovorin) 200 mg/m2 over 2 h on days 1 and 2. This was followed by an intravenous bolus injection of 5-FU 400 mg/m2 and then continuous intravenous infusion of 5-FU 600 mg/m2 over 22 h every 2 weeks. The schedule and dosage for FOLFOX4 regimen was the same in the two hospitals. Both chemotherapy regimens were meant to be given for 24 weeks, with eight cycles of EOX or 12 cycles of FOLFOX. However, they were also administered until disease progression or toxicity, if these conditions were reached before having finished the full number of cycles.
Data collection
Patient demographics, clinical characteristics such as Eastern Cooperative Oncology Group (ECOG) performance score and metastases, schedules of outpatient, inpatient and day ward visits, laboratory tests and procedures performed, as well as medications associated with chemotherapy administration were extracted from electronic patient records. Data on medications used during hospitalizations were gathered from patient medical charts, whereas adverse events related to the chemotherapy were taken down from doctors’ progress notes.
Cost evaluation
Healthcare provider’s perspective
Costs under healthcare providers’ perspective are known as direct medical costs, which include all the costs for clinic visits, follow-up, hospitalization, as well as laboratory investigations and medications used in either inpatient or outpatient settings. Expected costs only include the costs directly associated with chemotherapy administration. From the electronic patient records, the hospital bed-days required for delivery of EOX and FOLFOX4 chemotherapy were 1 and 3, respectively. FOLFOX4 patients were admitted at 9 am on Day 1 and discharged at 3 pm on Day 3. Therefore, any further days of hospitalization and the associated laboratory tests performed and medications consumed were classified as unexpected costs. Any walk-in clinic visits, specialist clinic visits due to delay of chemotherapy, and Accident & Emergency Department (AED) visits were also deemed as unexpected. All adverse event costs were also included within these unscheduled costs.
The costs for healthcare resources usage, including hospital visits and laboratory investigations, were valued according to the Hong Kong Government Gazette 2003Citation12, which is the most updated version of the official source for costs of public hospital services. The charges for different hospital services are listed as follows: specialist outpatient visits = HK$700(US$87.50), general outpatient visits = HK$215(US$26.90), AED visits = HK$570(US$71.30), inpatient stay = HK$3,300(US$412.50) per day, day procedure at Clinical Oncology Clinic = HK$600(US$75). These prices are regarded as the expected costs incurred by the healthcare provider to provide these services. The costs for any services consumed by patients at the private hospital sector were also valued based on the costs at the public hospital sector. Medication costs were calculated based on drug acquisition costs of the hospital, which were obtained from PMH and PYNEH procurement lists in 2011. All costs were expressed in US dollars (1 US$= 8.00 HK$).
Societal perspective
Costs under societal perspective are known as indirect medical costs, which include patients’ time and travel costs spent during outpatient visits, AED visits, and hospitalization. Apart from the time spent in administration of EOX regimen at day ward as well as AED visits, the time consumed during other hospital visits were estimated only, as actual information was not able to be extracted from patient medical records. Both specialist and general outpatient visits were estimated to take 2 h every time, while time to carry out laboratory investigations was estimated to be 1 h. Time costs for the above were calculated based on the median hourly wages of different sex and age groups in Hong Kong. For the time costs spent by patients during hospitalization, they were calculated by multiplying the number of hospital bed-days with the daily salary estimated, based on the median monthly employment earnings of all employed persons of different sex and age groups in Hong KongCitation13 (see Appendix I).
As for the estimation of travel costs, they were calculated based on the urban taxi fare for the distance between the home address of patients and their respective institution. The distance was estimated with Google Maps, while the taxi fare was calculated according to the fare table issued by the Transport Department in Hong KongCitation14 (see Appendix II).
Sub-group analysis
Two sub-group analyses were performed to test the robustness of this cost model. The first one was to evaluate the total healthcare and societal cost of EOX and FOLFOX4 regimens when the full number of cycles was carried out. This would mean a total of eight cycles of EOX and 12 cycles of FOLFOX4 were given. The second analysis was to assess the actual and the full cycle healthcare cost of EOX and FOLFOX4 group after removing the costs of epirubicin, oxaliplatin, associated pre-medications, as well as liquids for infusion. This aimed to investigate the net effect of capecitabine and 5-FU/leucovorin on the total healthcare cost.
Statistical analysis
All data was analyzed with the statistical software Statistics Package for Social Sciences (SPSS for Windows, version 19.0, 2010, SPSS Inc., Chicago, IL). The distributions of all data were compared by Mann-Whitney U-test. Also, due to the uneven distribution of patients in each group (45 EOX vs 13 FOLFOX4), a p-value less than .01 was considered as statistically significant, in which the null hypothesis assuming there was no difference between the two groups would be rejected. Means and standard deviations were used to describe all the statistics.
Results
Patient baseline characteristics
A total of 58 subjects were identified, with only 13 in the FOLFOX4 arm. More patients seem to have chosen EOX over FOLFOX4 to avoid the inpatient stay for the prolonged administration of FOLFOX4. The two groups were then arranged for comparison in an approximate 3:1 ratio (45 EOX and 13 FOLFOX4). shows the baseline characteristics of patients in EOX or FOLFOX4 treatment arms. There is no difference in terms of gender distribution, median age, body surface area, performance status, percentage with metastasis when diagnosed, and median survival since diagnosis. More patients who received EOX had an ECOG performance status score of 0 or 1 than the FOLFOX4 group (p > .01).
Table 1. Baseline characteristics of patients in both groups.
Treatments
The full number of cycles for EOX and FOLFOX4 regimens was eight and 12, respectively. However, a number of patients experienced either disease progression or toxicity before reaching full cycles. As a result, only an average of 5.3 cycles of EOX and 7.9 of FOLFOX4 were given among the patients. This yields a completion rate of 66.3% for the EOX group, and 65.8% for the FOLFOX4 group. In addition, a majority of patients received dosage reduction throughout their treatment. In the EOX group, an overall of 83.3% dose of epirubicin, 90.6% of oxaliplatin, and 80.7% of capecitabine were given to the patients. On the other hand, in the FOLFOX group, patients received an overall dosage reduction for oxaliplatin and 5-FU/leucovorin of 86.7% and 92.5%, respectively.
Use of healthcare resources
indicates the pattern of healthcare resources used by patients in both groups during the whole period of treatment and their associated follow-up period for the last cycle. There was a statistically significant difference in the usage of medications between patients in both groups. The number of drug items necessary for chemotherapy delivery was fewer for EOX group than FOLFOX4 group by 3 (5.3 for EOX and 8.2 for FOLFOX4). The usage of unexpected medications per patient was also found to be less frequent for the EOX group (7.8 for EOX and 14.1 for FOLFOX4). Both differences were found to be statistically significant. Besides, there was also a significant difference in the hospitalization between both groups. The average expected hospital bed-days for FOLFOX4 patients were more than 4-times higher than that for EOX patients (5.3 days for EOX and 23.5 days for FOLFOX4). The usage of hospital services including specialist outpatient clinic, general outpatient clinic, A&E department, laboratory tests, as well as radiological examinations such as X-rays and scans did not differ significantly between the two groups.
Table 2. Healthcare resources used by patients in both groups.
Comparison of costs of treatment
Healthcare costs
shows the healthcare costs spent in both groups. Among all types of expected costs, only the cost for radiological investigations was not proven to have a statistically significant difference between EOX and FOLFOX4 groups. For the EOX arm, the average expenditure on expected medications, laboratory tests, and outpatient visits were all significantly higher than those incurred in the FOLFOX4 treatment arm. As a result, compared with patients in the FOLFOX4 group, patients in the EOX group spent ∼4-times more on medications, and 1.3-times more on both laboratory investigations and outpatient visits. Nevertheless, the money that EOX patients spent on hospital days required for chemotherapy delivery was 16.5-times less than that for FOLFOX4 patients (US$600 vs US$9,900). Overall, the sum of money that was used in the EOX group as chemotherapy related costs was US$5,854.4 per cycle and US$30,963.1 per patient, which was 54.9% and 69.6% less than the corresponding costs in the FOLFOX4 group (US$12,979.8 and US$101,841.3). As far as unexpected costs are concerned, the inpatient stay cost per cycle of chemotherapy for FOLFOX4 was higher than that for EOX.
Table 3. Healthcare cost for patients in both groups.
The total healthcare cost spent per patient, with the expected healthcare cost in particular, was higher for the FOLFOX4 group than for the EOX group. EOX patients spent a total of US$44,397.1 on direct medical costs, whereas FOLFOX4 patients spent a total of US$135,387.9, indicating that the EOX regimen was ∼67.2% less expensive than the FOLFOX4 regimen, from the perspective of healthcare provider. A net cost savings of more than US$90,000 was generated by giving the EOX regimen.
For both groups, nausea and vomiting were the most commonly associated adverse events; hence, the most frequently used medications were anti-emetic drugs. Metoclopramide tablets, famotidine tablets, and dexamethasone tablets were the most common anti-emetics prescribed to EOX patients, while metoclopramide tablets and injections were more common in the FOLFOX4 group. In the EOX group, the second most common adverse event was grade 1–2 hand foot syndrome and diarrhea, followed by myelosuppression and peripheral neuropathy. As for FOLFOX4 group, the second most common adverse event was grade 1–2 peripheral neuropathy, followed by constipation, bone marrow suppression, and phlebitis.
Societal costs
shows the societal costs spent in both groups. It is found that patients’ time cost was higher for the FOLFOX4 group, while their travel cost was higher for the EOX group. The patient treatment cost includes the cost of oxaliplatin injections for each respective regimen/dose, as well as the day-ward stay or inpatient stay costs responsible to be paid by the patients.
Table 4. Societal cost for patients in both groups.
Statistically significant differences were proven in all expected societal costs, but in none of the unexpected costs. Overall, the total indirect medical cost per patient for the EOX group, including both expected and unexpected costs, was 25.3% lower than that for the FOLFOX4 group (US$24,105.9 vs US$32,253.4).
Sensitivity analyses
Full cycle costs
Assuming that the full eight and 12 cycles had been administered successfully, along with the cost of medication, the total cost for healthcare provider and society combined should be $103,618.4 for EOX and $255,706.8 for FOLFOX4. The reduction in cost for giving EOX is now 59.5% instead. Thus, using the full number of cycles of the drugs would not change the relative cost-effectiveness.
Healthcare costs based on net cost for capecitabine or 5-FU/leucovorin
The healthcare cost analysis was calculated after removing the acquisition costs of epirubicin, oxaliplatin, pre-medications, and fluids for infusion, and leaving only capecitabine, 5-FU, and leucovorin costs for comparison. Results showed that the net medication cost difference between the EOX and FOLFOX4 groups has become larger, with the drug cost in the EOX group increasing from 2- to 3.5-times higher than the FOLFOX group for each cycle ($1463.3 vs $412.6). However, a higher total expected cost per cycle and for each patient was still achieved by the FOLFOX4 group. As far as the overall healthcare costs per patient, including both expected and unexpected, were concerned, the EOX regimen was 69.5% less expensive than FOLFOX4 regimen.
Discussion
Findings favoring the FOLFOX regimen
From the resultant findings, as far as expected chemotherapy drug cost is concerned, the FOLFOX4 regimen was more favourable, as the cost is only half of that for the EOX regimen. This is because capecitabine is a newer drug than 5-FU, hence the acquisition cost for capecitabine tablets is higher than that for 5-FU and leucovorin injectables. In addition, the FOLFOX group was discovered to have a lower expected cost for laboratory investigations. This is because EOX is a tri-weekly regimen, while FOLFOX4 is bi-weekly. Due to the shorter interval between each FOLFOX4 cycle, fewer laboratory tests, including biochemistry and hematology investigations, than the EOX group were necessary to monitor patients’ conditions for each cycle. Nevertheless, the total number of laboratory tests performed for both groups did not have a significant difference.
For the expected patient travel cost, although the difference was relatively less significant, FOLFOX4 patients seemed to pay less. This was because three of the patients in the EOX group lived relatively far away from the hospital, rendering the mean travel cost to be higher as a result. Besides, a lot of patients in the EOX group had their blood taken for laboratory tests on the previous day before follow-up at a specialist outpatient clinic, while all patients in the FOLFOX4 group had their blood test done on the same day as follow-up. Therefore, EOX patients had to pay extra travel costs for blood tests, which may account for the higher expenses in transport as well. Nevertheless, the total number of hospital visits intended for chemotherapy delivery or follow-up was in fact similar for both groups (18.4 vs 19.3).
Findings favoring the EOX regimen
According to the results, EOX therapy is more favorable in terms of expected hospitalization cost and time cost for delivery of chemotherapy. Among all the chemotherapeutic drugs of interest in this study, all of them are given intravenously except capecitabine, which is the only oral agent that can be taken by patients in the form of tablets. Therefore, a great difference in the necessary hospitalization time for intravenous chemotherapy delivery might be observed in the EOX and FOLFOX4 group, thus accounting for the significant difference in the number of expected hospital bed-days and their associated costs between both groups. Due to less time for intravenous administration, the lower expected time cost found for the EOX patients than the FOLFOX4 patients could also be explained. In addition, intravenous agents are always administered, together with additional items like solvents, water for injections, fluids for infusion, and/or heparin block set (also known as saline drip) for flushing purpose. For instance, epirubicin is given via normal saline running drip, oxaliplatin is administered in 5% dextrose solution, while leucovorin and 5-FU are given in normal salineCitation15. Since less intravenous administration is involved in the EOX regimen, the usage as well as the corresponding cost of these subsidiary items was also lower than the FOLFOX4 group, hence justifying the results.
Findings in unexpected costs
The number of unexpected medications taken by FOLFOX4 patients was discovered to be higher than EOX patients, indicating patients in the FOLFOX4 group had used more drugs for treatment or prevention of adverse events. Since capecitabine is more selective to tumor cells than 5-FU, EOX might have fewer adverse effectsCitation16,Citation17. Epirubicin and oxaliplatin are agents of moderate emetic risk (30–90% frequency of emesis), whereas capecitabine and 5-FU are of low emetic risk (10–30% frequency of emesis)Citation18. Combination therapy, hence, makes EOX and FOLFOX regimens highly emetic (>90% frequency)Citation18. Therefore, nausea and vomiting were the most commonly observed side-effects in both groups. Peripheral neuropathy (dose-limiting toxicity (DLT) of oxaliplatin), together with myelosuppression (DLT of epirubicin and 5-FU), were also noted in both groups. Due to slow marrow recovery leading to neutropenia, patients sometimes had to delay the next chemotherapy cycle and attend additional follow-ups, which caused an increase in unexpected cost. Hand foot syndrome and diarrhea were more frequently seen in the EOX group, since these are the DLTs of capecitabine. In addition, superficial phlebitis was another adverse event that was noted more commonly in FOLFOX4 than EOX patients. It is one of the major complications of intravenous administration as a result of infection at the site of catheter insertionCitation19. The catheter should be removed as soon as possible, as prolonged insertion is associated with a greater risk of insertion-site infection, which would in turn bring about complications like phlebitis, cellulitis, and even sepsisCitation19. Since FOLFOX4 requires more than 50 h for intravenous delivery, while EOX only requires several hours, the risk of superficial phlebitis is actually higher in the FOLFOX group, which might lead to a higher unexpected management cost.
Comparison with other studies
From the results of this study, it was discovered that, although the purchase price of the EOX regimen was nearly twice as expensive as the FOLFOX4 regimen, EOX was indeed the more cost-effective one in Hong Kong when all other usage of healthcare resources were taken into consideration. The sub-group analysis based on the net cost of capecitabine vs 5-FU/leucovorin even provides further demonstration on the cost-saving effects of capecitabine. The total direct medical expenses could save up to 60% for EOX therapy, and the total indirect societal costs could also be reduced by more than 40%. These findings were consistent with the study conducted by Giuliani et al.Citation20 in 2007, which evaluated the economic impact of capecitabine plus cisplatin (XP) and 5-FU plus cisplatin (FP) regimens on the treatment for advanced gastric cancer in an Italian setting. Although the regimens compared are not exactly the same for both studies, the targeted therapies were still either being a capecitabine-based or 5-FU-based treatment with the involvement of a platinum agent. Therefore, comparison could still be considered applicable. The Italian study also revealed oral capecitabine to be capable of saving both healthcare and societal costs, by reducing the hospital bed-days required for infusion and time spent in receiving treatmentCitation20. A similar cost-minimization study on capecitabine-based and 5-FU-based regimens in colorectal cancer management has also been performed by Tse et al.Citation21 in Hong Kong. Since both gastric cancer and colorectal cancer belong to gastrointestinal diseases which are treated with similar chemotherapeutic drugs, comparison between these two studies could be workable as well. XELOX (oxaliplatin plus capecitabine) and FOLFOX4 (same as FOLFOX4 in gastric cancer) regimens were compared in Tse et al.’sCitation21 study, the result of which also showed XELOX to cost less than FOLFOX4, due to less usage of hospital resources. As a result, it can be concluded from the above studies that capecitabine is indeed able to promote cost savings from both healthcare and societal perspectives.
Limitations
There are several limitations concerning this study. First of all, the uneven distribution of patient cases in each regimen arm and the small sample size. However, this was already the maximum number of cases that can be retrieved from the databases in the two hospitals. EOX and FOLFOX4 regimens are not adopted in all public hospitals in Hong Kong for patients with aGC. In Hong Kong, there are only seven hospitals with clinical oncology services provided. Among these seven hospitals, PMH and PYNEH are the few that are known to use both EOX and FOLFOX4 regimens.
Second, two patients in the EOX group were admitted to other public and private hospitals in Hong Kong for care during the treatment period, as a result of adverse events. Since the inpatient records at these hospitals were not accessible at the time of this study, the healthcare resources or services used by patients during the hospitalization period, such as medications, laboratory tests, and radiological examinations, were unknown. Therefore, this would lead to an under-estimation of unscheduled healthcare costs in the EOX arm.
Finally, as quite a large number of patients were elderly, they may have some caretakers from their families or friends to take care of their daily life, including hospital and clinic visits. These caretakers have probably accompanied the patients for the chemotherapy delivery, outpatient visits, as well as laboratory tests and procedures. However, there has been no information concerning their time costs and travel costs. As a result, both expected and unexpected societal costs may be under-estimated. Nevertheless, if these data were taken into consideration as well, the savings on the EOX regimen compared with the FOLFOX4 regimen could become greater, since the caretakers may spend less time on the administration of EOX therapy.
Conclusion
From a healthcare provider’s perspective, EOX is more cost-effective than FOLFOX4, given similar efficacy and adverse event outcomes, as indicated from previously published trials in regions in which FOLFOX4 is given in an inpatient setting. Although the apparent cost per dose is higher for EOX, most patients require fewer cycles than that required by the FOLFOX4 regimen. Added to this is the saving in hospital costs due to the route of administration of capecitabine vs 5-FU/leucovorin. EOX also imposes fewer costs on the patient, and results in fewer days lost from work. Altogether with provider and societal costs combined, the capecitabine-based regimen, EOX, is cost-effective compared to the 5-FU-based regimen, FOLFOX4, and should be advocated when appropriate.
Transparency
Declaration of funding
This project was funded by Roche (Hong Kong) Company Ltd.
Declaration of financial/other relationships
KRZ and VWYL report receiving research funding from Roche Hong Kong. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Acknowledgement
The authors thank colleagues at the Clinical Oncology Department, Princess Margaret Hospital, and Pamela Yonde Nethersole Eastern Hospital.
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Appendix I. Median wages in Hong Kong
Wage levels for different age and sex groups in Hong Kong (HK$).