Comparison of target agent treatment strategies for platinum-resistant recurrent ovarian cancer: A Bayesian network meta-analysis.

BACKGROUND: We aimed to compare 7 newer immunotherapies and targeted therapies for platinum-resistant relapsed ovarian cancer. METHODS: We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library electronic databases for phase III trials involving platinum-resistant recurrent ovarian cancer (PRrOC) patients treated with immunotherapy or targeted therapy in combination with chemotherapy. The quality of the included trials was assessed using the GRADE method. The primary outcome of comparison was progression-free survival, and secondary outcomes included overall survival and safety. RESULTS: This analysis included 7 randomized phase III controlled trials, encompassing 2485 PRrOC patients. Combining bevacizumab plus chemotherapy and lurbinectedin demonstrated statistically significant differences in progression-free survival compared to all other regimens of interest. However, no statistically significant differences were observed in the overall survival. Nivolumab and mirvetuximab exhibited fewer serious adverse events than the other regimens of interest. CONCLUSIONS: Our findings indicate that bevacizumab combined with chemotherapy and lurbinectedin monotherapy has significant efficacy in patients with PRrOC. For patients with PRrOC who have exhausted treatment options, nivolumab and mirvetuximab may be considered as alternatives because of their better safety profiles.

Comparative efficacy and safety of multimodality treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus: patient-level network meta-analysis.

Background: Portal vein tumor thrombus (PVTT) is a common complication and an obstacle to treatment, with a high recurrence rate and poor prognosis. There is still no global consensus or standard guidelines on the management of hepatocellular carcinoma (HCC) with PVTT. Increasing evidence suggests that more aggressive treatment modalities, including transarterial chemoembolization, radiotherapy, targeted therapy, and various combination therapies, may improve the prognosis and prolong the survival of advanced hepatocellular carcinoma (aHCC) patients with PVTT. We aim to comprehensively review and compare the efficacy and safety of these advanced options for aHCC with PVTT. Methods: A comprehensive literature search was conducted on PubMed and EMBASE for phase II or III randomized controlled trials (RCTs) investigating multimodality treatments for aHCC with PVTT. Kaplan-Meier curves for overall survival (OS) and progression-free survival were constructed to retrieve individual patient-level data to strengthen the comparison of the benefits of all multimodality treatments of interest. Each study was pooled in a fixed-effects network meta-analysis (NMA). We also conducted subgroup analyses using risk ratios extracted from each study, including viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion or portal vein tumor thrombosis, and extrahepatic spread. Multimodality treatments were ranked using SUCRA scores. Results: We identified 15 randomized controlled trials with 16 multimodality regimens that met the inclusion criteria. Among them, 5,236 patients with OS results and 5,160 patients with PFS results were included in the analysis. The hepatic arterial infusion chemotherapy of fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) showed OS and PFS benefits over all the other therapies. In terms of OS, HAIC-FO, nivolumab, and TACE+Len were superior to sorafenib, lenvatinib, and donatinib monotherapies, as well as HAIC-FO+Sor. In terms of PFS, TACE+Len showed better benefits than lenvatinib, donatinib, and tremelimumab+durvalumab. A low heterogeneity (I 2 < 50%) and consistency were observed. The SUCRA score for OS ranked HAIC-FO+sorafenib as the best treatment option among all multimodality treatments in hepatitis B, MVI, or PVTT with EHS and AFP 400 µg/L subgroups. Conclusion: HAIC-FO and HAIC-FO+sorafenib are statistically better options for unresectable hepatocellular carcinoma with PVTT among the multimodality treatments, and their effective and safe implementation may provide the best outcomes for HCC-PVTT patients.

Hypothyroidism and hyperthyroidism related to gynecologic cancers: a nationwide population-based cohort study.

The purpose of this study was to assess the risks of hyperthyroidism and hypothyroidism related to gynecological cancers. Population-based retrospective cohort study. We conducted a cohort study using the Taiwan National Health Insurance Research Database to explore hyperthyroidism and hypothyroidism associated with site-specific gynecologic cancers in women from January 1, 2000 to December 31, 2018. The examined gynecologic cancers included endometrial (EC), uterine corpus cancer (UC), and ovarian cancer (OC). The incidence and hazard ratios were quantified using Cox proportional hazards models. The incidence of developing gynecological (Gyn) cancers in the hyperthyroid and hypothyroid women was 0.29 and 0.44 per 1000 person-years, which was 0.86 fold lower and 1.13 fold higher than that in the comparison cohort (p < 0.001). Compared with patients aged 20-40 years, patients in older age groups had a lower and higher risk of developing Gyn cancers (for hyperthyroid, 40-65 years: adjusted hazard ratio (aHR) = 0.82; > 65 years: aHR = 0.94; for hypothyroid, adjusted hazard ratio (aHR) = 1.26; > 65 years: aHR = 1.38). Compared with the non-hypothyroid women and non-hyperthyroid women beyond 6 years of follow-up, hypothyroid and hyperthyroid women showed decreased risk of Gyn cancers. Medication treatment for hyperthyroid and hypothyroid disease did not showed significant association in subgroup analyses (aHR = 0.99 and 0.80, respectively). Our results show that women with hyperthyroidism have a significantly reduced risk of gynecological cancers, whereas women with hypothyroidism have a slightly increased risk of gynecological cancers suggesting an association between thyroid function level and risk of gynecological cancers.

Hepatic Arterial Infusion Chemotherapy Followed by Lipiodol Infusion for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Single-Center Experience.

Background and Objectives: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) followed by lipiodol infusion in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Materials and Methods: Thirty-two patients with advanced HCC and PVTT who received HAIC with regimens of cisplatin, mitomycin-C, and 5-fluorouracil followed by lipiodol infusion were enrolled. The primary efficacy endpoint was tumor response rate. The modified Response Evaluation Criteria in Solid Tumors (mRECIST) was used for assessment of treatment response. The secondary endpoints were overall survival (OS) and progression free survival (PFS). Prognostic factors for survival also were evaluated. Results: The median OS and PFS were 11.9 and 9.5 months, respectively. Seventeen patients (53.1%) achieved objective response, and 23 patients (71.9%) achieved disease control. The length of survival in the responder and disease control groups was longer than in the non-responder and progressive disease groups after two cycles of HAIC (responder vs. non-responder: 16.5 vs. 7.9 months, p = 0.001; disease control vs. progressive disease: 12.3 vs. 5.6 months, p < 0.001) and after completing HAIC (responder vs. non-responder: 15.7 vs. 6.9 months, p = 0.001; disease control vs. progressive disease: 13.6 vs. 6.9 months, p < 0.001). Better survival was associated with Child-Pugh A liver function (p = 0.013), with early response to two HAIC cycles (p = 0.009), and with response (p = 0.02) and disease control (p = 0.001) after completing HAIC treatment. Conclusion: HAIC followed by lipiodol infusion is a safe and feasible treatment for advanced HCC with PVTT. Patients with early response could continue HAIC treatment with expected prolonged survival.

Efficacy and safety of CDK4/6 and PI3K/AKT/mTOR inhibitors as second-line treatment in postmenopausal patients with hormone receptor-positive, HER-2-negative metastatic breast cancer: a network meta-analysis.

BACKGROUND: We compared the efficacy and safety of combinations of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and PI3K/AKT/mTOR inhibitors as second-line treatment in postmenopausal women with HR+, HER2- metastatic breast cancer. METHODS: We searched the Medline, Embase, and Cochrane Library electronic databases for phase II/III randomized trials evaluating CDK4/6 and PI3K/AKT/mTOR inhibitors plus fulvestrant. We compared the results with a network meta-analysis. Study quality was assessed following the GRADE approach. Outcomes of interest were progression-free survival, overall response rate, overall survival and G3-4 adverse drug events (ADEs). RESULTS: Eight RCTs were identified in the network meta-analysis. PFS was significantly improved by treatment with abemaciclib plus fulvestrant and ribociclib plus fulvestrant compared to pictilisib plus fulvestrant. The ORR following treatment with abemaciclib plus fulvestrant, ribociclib plus fulvestrant, palbociclib plus fulvestrant, buparlisib plus fulvestrant, and alpelisib plus fulvestrant significantly differed from that observed following treatment with placebo plus fulvestrant. In terms of OS, compared with placebo plus fulvestrant, abemaciclib plus fulvestrant, ribociclib plus fulvestrant, and buparlisib plus fulvestrant had a significant difference. The risks of ADEs were similar among three CDK4/6 inhibitors. CONCLUSION: As second-line treatment, three CDK4/6 inhibitors showed superior clinical efficacy compared to other PI3K/AKT/mTOR inhibitors with comparable safety profiles.

Cost-effectiveness of pertuzumab combined with trastuzumab and docetaxel as a first-line treatment for HER-2 positive metastatic breast cancer.

OBJECTIVE: To provide perspective for the National Health Insurance Bureau (NHIB), we determined the cost-effectiveness of pertuzumab combined with trastuzumab and docetaxel (TDP) versus trastuzumab and docetaxel (TD) as a first-line treatment for HER-2 positive metastatic breast cancer. METHODS: We used a Markov model to simulate cost-effectiveness, disease progression, and survival, based on clinical data and transition probabilities extracted from the CLEOPATRA study. Direct medical costs were acquired from the NHIB claims database.The utilities in health state were based on a recent cost-effectiveness study on trastuzumab and pertuzumab. Outcomes included quality-adjusted life-years (QALYs), costs in New Taiwan dollars (NT$), and the incremental cost-effectiveness ratio (ICER). We performed one-way deterministic and probabilistic sensitivity analyses to assess the impact of specific parameters on the model. RESULTS: Modeled median survival was 39.1 months for TD and 50.1 months for TDP. The ICER was NT$18,999,687 (US$593,741) per QALY gained. The sensitivity analyses indicated that TDP could be cost-effective under favorable assumptions; TDP had a 68% chance of being cost-effective, if TDP costs could be reduced with 10% in the stable disease state. CONCLUSION: Our model predicted that TDP would be cost-effective as a first-line treatment for HER-2 positive metastatic breast cancer, but only under favorable drug cost assumptions.

Efficacy and safety of a combination of HER2-targeted agents as first-line treatment for metastatic HER2-positive breast cancer: a network meta-analysis.

BACKGROUND: Using network meta-analysis, we assessed the efficacy and safety of a combination regimen of HER2-targeted agents as first-line treatment for metastatic HER2-positive breast cancer. METHODS: We searched the Medline, Embase, and Cochrane Library electronic databases (through December 2016) for phase II/III randomized controlled trials that compared regimens of one or two HER2-targeted agents combined with trastuzumab or chemotherapy. A network meta-analysis including direct and indirect analyses was conducted in WinBUGS using fixed and random effects. Study quality was assessed following the Grading of Recommendations, Assessment, Development and Evaluations method. The primary outcome was overall survival. RESULTS: The network meta-analysis incorporated nine HER2-targeted regimens with 9 direct comparisons and 28 indirect comparisons for the main outcomes (8 studies; n = 3976). Combining direct and indirect effects showed significant increased efficacy of trastuzumab and docetaxel plus pertuzumab (TDP) over other regimens as first-line treatment. With indirect comparison of overall safety, TDP, TDM-1, and TDM-1 plus pertuzumab demonstrated a lower risk of grade 3-4 adverse events compared to other regimens. CONCLUSIONS: TDPs are a preferred first-line treatment for HER2-positive metastatic breast cancer compared with other target agent regimens.

Cost-utility of stereotactic radiation therapy versus proton beam therapy for inoperable advanced hepatocellular carcinoma.

The cost-utility of proton beam therapy was compared to stereotactic body radiation therapy for inoperable advanced hepatocellular carcinoma. A Markov decision-analytic model was performed following time to progression and survival using phase II trial data. Patients transitioned between three health states. Clinical outcomes were estimated for quality of life using utility estimates in the published literature and measured as incremental cost-effectiveness ratios (ICERs) and net monetary benefits (NMBs). Real direct medical costs were extracted from the Bureau of National Health Insurance database. One-way and probabilistic sensitivity analyses assessed the impact of specific variables on the model. In the base-case scenario, the modeled median survival was 16 months for proton beam therapy and 10 months for SBRT. Proton beam therapy resulted in an additional 2.61 quality-adjusted life years (QALYs) at an incremental cost of NT$ 557,907 compared to SBRT. The ICER was NT$ 213,354 per QALY gained. The probabilistic sensitivity analysis predicted a 97 % chance of proton beam therapy being cost-effective at the willingness to pay NT$2,157,024 per QALY gained. Thus, proton beam therapy is a cost-effective therapy for inoperable advanced hepatocellular carcinoma at the willingness-to-pay threshold of Taiwan.

Cost-effectiveness of sorafenib versus SBRT for unresectable advanced hepatocellular carcinoma.

OBJECTIVE: Stereotactic body radiotherapy (SBRT) has been shown to improve overall survival in patients with advanced hepatocellular carcinoma. This study aimed to assess the cost-effectiveness of SBRT compared to sorafenib which is the only drug for advanced hepatocellular carcinoma. METHODS: A Markov decision-analytic model was performed to compare the cost-effectiveness of SBRT and sorafenib for unresectable advanced hepatocellular carcinoma. Patients transitioned between three health states: stable disease, progression disease and death. We calculated the data on cost from the perspective of our National Health Insurance Bureau. Sensitivity analyses were conducted to determine the impact of several variables. RESULTS: The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was NT$3,788,238 per quality-adjusted life year gained (cost/QALY), which was higher than the willingness to pay threshold of Taiwan according to WHO's guideline. One-way sensitivity analysis revealed that the utility of progression disease for the sorafenib treatment, utility of progression free survival for SBRT, utility of progression free survival for sorafenib, utility of PFS to progression disease for SBRT and transition probability of progression disease to dead for SBRT were the most sensitive parameters in all cost scenarios. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of NT$ 2,213,145 per QALY was 100 % and 0 % chance for SBRT and sorafenib. CONCLUSION: This study indicated that SBRT for advanced hepatocellular carcinoma is cost-effective at a willingness to pay threshold as defined by WHO guideline in Taiwan.

Cost-effectiveness of Gemcitabine Plus Modern Radiotherapy in Locally Advanced Pancreatic Cancer.

PURPOSE: The purpose of this study was to evaluate the cost-effectiveness of gemcitabine plus modern radiotherapy versus gemcitabine alone in the treatment of locally advanced pancreatic cancer in Taiwan. METHODS: A Markov decision-analytic model was performed to compare the cost-effectiveness of 3 treatment regimens; gemcitabine alone (gem-alone), gemcitabine plus intensity-modulated radiotherapy (gem-IMRT), and gemcitabine plus stereotactic body radiotherapy (gem-SBRT). Patients transitioned between 5 health states: stable disease, local progression, distant metastasis, local and distant metastasis, and death. FINDINGS: The incremental cost-effectiveness ratio for gem-IMRT and gem-SBRT compared with gem-alone were NT$27,120,168 and NT$2,145,683 per quality-adjusted life-year gained, respectively. A willingness to pay threshold of 3 times the per capita gross domestic product was adopted according to the definition of the World Health Organization. The Taiwan per capita gross domestic product in 2015 was NT$673,920 (US$22,464; 1 NT$ = US$0.03333 in Taiwan); thus, a threshold was considered as NT$2,021,760 (US$67,392). The Monte-Carlo simulation found that the probability of cost-effectiveness at a willingness to pay threshold of NT$2,021,760 per quality-adjusted life-year was 0% chance for gem-IMRT and 50% for gem-SBRT. IMPLICATIONS: This study indicated that gem-IMRT or gem-SBRT in locally advanced pancreatic cancer is not cost-effective at a willingness to pay as defined by World Health Organization guideline in Taiwan.

Glutamine in Alleviation of Radiation-Induced Severe Oral Mucositis: A Meta-Analysis.

The aim of this meta-analysis was to assess the effectiveness of glutamine to treat severe mucositis induced by radiation therapy in patients with head and neck cancer. We undertook electronic searches of PubMed (1990 to January 2015), Embase (1990 to January 2015), and the Cochrane Library (2013, Issue 2) to identify relevant studies. We included randomized controlled trials of glutamine to alleviate oral mucositis (OM) in patients with head and neck cancer who received radiotherapy. Information regarding methods, patients, results, and risk of bias was independently extracted by two authors. Statistical analyses were conducted to calculate the odds ratio and 95% confidence intervals (95%CIs) using fixed-effect models. We identified five clinical studies that included 234 patients with head and neck cancer. All studies were assessed as being at low risk of bias in most items of six domains. In this meta-analysis, glutamine treatment showed a statistically significant benefit with respect to reducing the risk and severity of OM induced by radiotherapy compared to either placebo or no treatment (risk ratio 0.17, 95%CI 0.06-0.47). Overall, glutamine significantly reduces the risk and severity of OM during radiotherapy or chemotherapy. Further prospective and large trials are required to support the findings.

Late cardiac morbidity of adjuvant radiotherapy for early breast cancer - A population-based study.

PURPOSE: The purpose of this study was to assess the long-term cardiac morbidity and mortality after breast irradiation using contemporary irradiation techniques. METHODS: We used the Catastrophic Illness dataset from the National Health Insurance Research Database to explore the possible association between late cardiotoxicity and women with early breast cancer treated with breast conservation therapy from 2000 to 2010. The Cox proportional-hazards model was used to compare breast cancer patients who received adjuvant radiotherapy versus without adjuvant radiotherapy for the end points with the following primary diagnoses (International Classification of Diseases, 9th Revision codes): ischemic heart disease (410-414, 36.0, 36.1), valvular heart disease (394-397, 424, 35), congestive heart failure (428, 402.01, 402.11, 402.91), and conduction abnormalities (426, 37.7-37.8, 37.94-37.99). RESULTS: Three hundred and thirty patients received adjuvant radiotherapy and 4802 patients did not receive radiotherapy. Median follow-up was 3.5 years. There was no difference in overall morbidity and mortality from any cardiac cause (p=0.13) in breast cancer patients who received adjuvant radiotherapy versus without radiotherapy by using modern radiotherapy techniques. CONCLUSION: There were no significant differences in cardiac morbidity and mortality after radiotherapy for breast cancer with a 9-year follow-up period in our population.

Association and prediction of severe 5-fluorouracil toxicity with dihydropyrimidine dehydrogenase gene polymorphisms: A meta-analysis.

The aim of the present study was to evaluate the association and prediction of dihydropyrimidine dehydrogenase gene (DPYD) polymorphisms and the risk of 5-fluorouracil (5-FU) severe toxicity in cancer patients. A meta-analysis of the published literature was conducted to summarize evidence for DPYD gene polymorphisms associated with an increased risk of severe 5-FU toxicity in patients with cancer from an Asian population. Relevant literature was identified using the PubMed and Cochrane databases on April 11, 2014. Combined risk ratios and 95% confidence intervals (CIs) were calculated in a fixed-effects model. A total of 5 clinical studies were retrieved in the meta-analysis, including 764 cancer patients with DPYD gene polymorphisms who received 5-FU-based chemotherapy. Overall, DPYD gene polymorphisms were associated with the increased risk of 5-FU severe toxicity [risk ratio=2.54 (2.15-3.00); 95% CI, 19.46-84.57; P=0.0001]. In conclusion, the present meta-analysis suggested that polymorphisms of several DPYD gene polymorphisms are associated with an increased risk of severe toxic response to 5-FU.

Trastuzumab-induced cardiotoxicity in elderly women with HER-2-positive breast cancer: a meta-analysis of real-world data.

BACKGROUND: We conducted a meta-analysis to assess the overall risk of cardiac toxicity associated with trastuzumab treatment in elderly breast cancer patients. METHODS: We searched databases from PubMed, EMBASE and Cochrane Central Registry of Controlled Trials to identify relevant studies. Statistical analyses were conducted to calculate the incidence rate, overall hazard ratio (HR) and 95% CIs using a fixed effects model. RESULTS: A total of 116,342 and 360 elderly patients from five cohort studies and two randomized clinical trials (RCTs) were included for analysis. The pooled incidences of symptomatic congestive heart failure (CHF) and CHF/HF/CM were 6.4% (95% CI 4.1% - 9.4) and 16.4% (95% CI 16.19% - 16.61) in patients with median age of 67.5 years from two RCTs and in patients with median age of 67.5 (60 - 75), 71 (66 - 80+), 74.5 (65 - 89), 75 (66 - 81+) and 79.5 (60 - 99) from five cohort studies, respectively. Trastuzumab was significantly correlated with an increased risk of defined cardiac toxicities in five cohort studies (HR = 1.89, 95% CI 1.72 - 2.07, p < 0.00001) and two RCTs (HR = 3.00, 95% CI 1.71, 5.26, p < 0.00001). Sub-group analysis showed that the anthracycline-based chemotherapy increased the risk of CHF/HF and CM in patients among five cohort studies (HR = 2.16, 95% CI: 1.8 - 1.87, p < 0.00001). CONCLUSION: Trastuzumab is likely associated with an increased risk of cardiac toxicity in elderly patients with HER-2-positive breast cancer. Carefully monitoring cardiac function in elderly patients receiving trastuzumab, particularly with concurrent use of anthracycline, is warranted.

Long-Term Use of Antihypertensive Agents and Risk of Breast Cancer: A Population-Based Case-Control Study.

INTRODUCTION: To evaluate the risk of breast cancer associated with long-term use of antihypertensive agents (AHs) in Taiwanese women with hypertension. METHODS: A search of the Taiwan National Health Insurance Research Database identified 330,699 patients with hypertension who were treated with antihypertensive drugs between January 1, 1998 and December 31, 2011. Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) between the use of AHs and breast cancer risk, adjusted for other types of antihypertensive drugs, statins and co-morbidities. RESULTS: Among the AHs used to treat the hypertensive women enrolled in our study, our analysis revealed that those treated with one specific particular class of beta-blockers (beta-1 selective beta-blockers) had an increased risk for breast cancer. We also found that the ever-use of calcium channel blockers (CCBs; i.e. for 13 years) was associated with breast cancer in an adjusted model (OR 1.09; 95% CI 1.03-1.16). However, the use of nonselective beta-blockers, selective and nonselective alpha-blockers, angiotensin-converting enzyme inhibitors and angiotensin II antagonists were not associated with breast cancer risk. CONCLUSION: Based on the results of our analysis, long-term use of CCBs or beta-1 selective beta-blockers are likely to be associated with the risk of breast cancer. Further large comprehensive population-based studies to support our findings are required for confirmation of this conclusion.

Indirect comparisons of efficacy and safety between seven newer targeted agents for metastatic renal cell carcinoma: A network meta-analysis of randomised clinical trials.

This network meta-analysis aimed to compare the clinical efficacy and safety among 7 newer targeted agents for the treatment of metastatic renal cell carcinoma (mRCC). All randomised clinical trials (RCTs) of targeted therapeutic drugs for mRCC were included. The study selection, data extraction and quality assessment were performed independently by two reviewers. The analysis evaluated efficacy outcomes [improvement in the median progression-free survival (PFS)] and safety outcomes (number of withdrawals due to adverse events). The network analysis included direct and indirect analyses. The quality of the selected studies was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. We identified 7 articles eligible for inclusion in the study. The direct comparison of the targeted agents indicated better efficacy in terms of longer PFS, but worse safety (more withdrawals due to adverse events). The indirect analysis demonstrated that axitinib was significantly more effective compared to panzopanib; sunitinib was superior to sorafenib and temsirolimus regarding efficacy outcome, without any statistically significant difference in the safety outcome. The results of the quality assessment indicated moderate scores using the GRADE method. In conclusion, the result of this network analysis suggested that sunitinib and axitinib may be more clinically efficient and axitinib is associated with a lower risk of adverse events compared to sorafenib, pazopanib and temsirolimus.

Systematic review and quality assessment of cost-effectiveness analysis of pharmaceutical therapies for advanced colorectal cancer.

OBJECTIVE: To systematically review and assess the quality of cost-effectiveness analyses (CEAs) of pharmaceutical therapies for metastatic colorectal cancer (mCRC). DATA SOURCES: The MEDLINE, EMBASE, Cochrane, and EconLit databases were searched for the Medical Subject Headings or text key words quality-adjusted, QALY, life-year gained (LYG), and cost-effectiveness (January 1, 1999-December 31, 2009). STUDY SELECTION: Original CEAs of mCRC pharmacotherapy published in English were included. CEAs that measured health effects in units other than quality-adjusted life years or LYG and letters to the editor, case reports, posters, and editorials were excluded. DATA EXTRACTION: Each article was independently assessed by 2 trained reviewers according to a quality checklist created by the Panel on Cost-Effectiveness in Health and Medicine. RESULTS: Twenty-four CEA studies pertaining to pharmaceutical therapies for mCRC were identified. All studies showed a wide variation in methodologic approaches, which resulted in a different range of incremental cost-effectiveness ratios reported for each regimen. We found common methodologic flaws in a significant number of CEA studies, including lack of clear description for critique of data quality; lack of method for adjusting costs for inflation and methods for obtaining expert judgment; no results of model validation; wide differences in the types of perspective, time horizon, study design, cost categories, and effect outcomes; and no quality assessment of data (cost and effectiveness) for the interventions evaluation. CONCLUSIONS: This study has shown a wide variation in the methodology and quality of cost-effectiveness analysis for mCRC. Improving quality and harmonization of CEA for cancer treatment is needed. Further study is suggested to assess the quality of CEA methodology outside the mCRC disease state.

Common cancer risk and statins: a population-based case-control study in a Chinese population.

OBJECTIVE: To investigate whether the use of statins is associated with common cancer risk. METHODS: A population-based case-control study was conducted in Taiwan. Cases were defined as all patients who were aged 18 years and older and had received at least two statin prescriptions for use continuously for at least 6 months before a first-time diagnosis of studied cancers between the period of 2000 and 2008. The controls were matched to cases by age, sex, and index date. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by using the Cox proportional hazards model. RESULTS: A total of 6841 cases and 27,364 matched controls were analyzed. The adjusted hazard ratio for any statin use and cancer at any site were 0.76 (95% 0.654, 0.891). There were a significant reduced risk of gastric cancer (HR: 0.26, 95% CI: 0.107, 0.588), liver cancer (HR: 0.44, 95% CI: 0.279, 0.723) and uterine cancer (HR: 0.44, 95% CI: 0.279, 0.723) associated with any statins. CONCLUSION: Overall, the statins suggested a significant reduced risk of the most common cancers in a large Chinese population, particularly in gastric, liver, and uterine cancers.

Cost effectiveness of cetuximab concurrent with radiotherapy for patients with locally advanced head and neck cancer in Taiwan: a decision-tree analysis.

BACKGROUND: Concomitant chemotherapy with radiotherapy is considered to be the standard of care for patients with head and neck cancer and good performance status. However, published reports on the cost effectiveness of this therapeutic approach are extremely rare. OBJECTIVE: The aim of this study was to estimate the cost effectiveness of cetuximab combined with radiotherapy compared with radiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck. METHODS: A decision-tree analysis was used to compare cetuximab combined with radiotherapy and radiotherapy alone in the treatment of patients with locally advanced squamous cell carcinoma of the head and neck from the perspective of the national health payer (the Bureau of National Health Insurance [BNHI]) in Taiwan. The model was based on individual patient data extracted from an international phase III trial. The direct medical costs of care were estimated by clinical expert panels based on the reimbursement price of the BNHI (2007 values). One-way sensitivity analyses were performed while varying the costs and clinical parameters. RESULTS: The incremental cost per quality-adjusted life-year (QALY) for patients receiving radiotherapy in combination with cetuximab compared with radiotherapy alone was $US36 992/QALY in the base-case analysis (2007 values). The sensitivity analysis showed the highest net benefit for radiotherapy alone if the cost of cetuximab increased by 50%. CONCLUSION: This study demonstrated that the addition of cetuximab to high-dose radiotherapy regimens is likely to be cost effective in Taiwan because the incremental cost per QALY is below the commonly accepted cost-effectiveness threshold.