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Purpose: In order to confirm the efficacy, tolerability, and baseline prognostic factors of an epirubicin (EPR)-containing triplet regimen, the EOF5 regimen, in patients with metastatic gastric cancer (MGC), we conducted the phase II trial and retrospective analysis. Methods: MGC patients received the EOF5 regimen (EPR 50 mg/m and oxaliplatin (OX) 130 mg/m on day 1 followed by continuous infusion of 5-fluorouracil (5-FU) 375-425 mg/m/days for 5 days every 3 weeks). Log-rank tests were used for univariate analysis of time to progression (TTP) and overall survival rate (OS), and stepwise Cox proportional hazards regression modeling was performed to generate a prognostic index. Results: A total of 158 patients received the EOF5 regimen. Of the 150 evaluable patients, complete remission, partial remission, and stable disease were observed in 5 (3.3 %), 70 (46.7 %), and 58 patients (38.7 %), respectively. The median TTP and OS were 6.0 (95 % CI 5.4-6.6) and 12.6 months (95 % CI 8.2-16.9), respectively. Grade 3-4 neutropenia (44.0 %), thrombocytopenia (25.3 %), and anemia (6.7 %) were recorded. A prognostic index that included liver and lung metastasis, ascites/pleural effusion, and baseline serum CA19-9 was used to categorize the patients into three groups: good risk (0 risk factors), moderate risk (1 or 2 risk factors), and poor risk (3 or 4 risk factors). The median OS for these groups was 30.4, 12.4, and 5.6 months, respectively ( P < 0.001). Conclusions: EOF5 is an effective regimen and a suitable alternative for the first-line treatment of MGC. According to the prognostic index used in our study, patients with no risk factors have a better OS when treated with EOF5 than those with one or more risk factors. [ABSTRACT FROM AUTHOR]

Abstract: Background: Bevacizumab has been extensively investigated in combination with various standard chemotherapies in the treatment of metastatic colorectal cancer (mCRC). However, a comparison to irinotecan + infusional 5-fluorouracil/leucovorin (FOLFIRI) is lacking. Objective: To explore clinical effectiveness and cost-effectiveness of adding bevacizumab to a regimen of FOLFIRI for the first-line treatment of mCRC in the Republic of Korea by conducting an indirect treatment comparison. Methods: A health-economic model was developed to investigate the possible health outcomes (life-years gained [LYG]), direct costs, and incremental cost-effectiveness ratio (ICER) of adding bevacizumab to a FOLFIRI regimen. Data on progression-free and overall survival were derived from randomized clinical trials and were used in the indirect treatment comparison. The annual discount rate for costs and outcomes was 5%. A lifetime horizon of 8 years was used. Sensitivity analyses were carried out on all pivotal model assumptions. Results: Incremental mean overall survival among patients treated with bevacizumab + FOLFIRI varied between 8.6 and 15.7 months compared with patients treated with FOLFIRI alone. The deterministic base-case result was 1.177 LYG. The discounted ICERs ranged from μ31.8 to μ39.5 million/LYG, with the base-case result being μ34.5 million/LYG. Treatment effect had the most impact on the outcomes in this model. Conclusions: Although there is no formal threshold for ICER per LYG in Korea, funding may be considered for bevacizumab + FOLFIRI, particularly if the severity and end-of-life nature of mCRC is taken into account. [Copyright &y& Elsevier]

The phase III AVAiL study evaluated the efficacy and safety of the anti-vascular epidermal growth factor agent bevacizumab combined with platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). We report the results of a preplanned analysis of Asian patients enrolled in AVAiL. Patients with recurrent or advanced non-squamous NSCLC were randomized to receive bevacizumab 7.5 mg/kg, bevacizumab 15 mg/kg or placebo, plus cisplatin 80 mg/m and gemcitabine 1250 mg/m for up to six cycles, followed by bevacizumab or placebo until disease progression. An exploratory analysis was undertaken to assess efficacy and safety in an Asian subgroup. Of the 1043 patients enrolled, 105 were Asian and were included in the subgroup analysis. Progression-free survival was 8.5 months (95% CI 7.3-10.8) in the bevacizumab 15-mg/kg group, 8.2 (95% CI 6.6-11.7) in the 7.5-mg/kg group and 6.1 (95% CI 5.1-8.0) in the placebo group. Median overall survival in the 7.5-mg/kg bevacizumab group was prolonged compared with placebo group (HR 0.46; 95% CI 0.22-0.97). Nausea was the most common adverse event, occurring at similar rates (ranging from 69-76%) in all study groups. Hypertension was the most common adverse event of special interest, seen in 29, 55 and 16% of patients in the 7.5-mg/kg and 15-mg/kg bevacizumab and placebo groups, respectively. Study results strongly suggest that bevacizumab at a dose of 7.5 mg/kg improves the duration of overall survival when combined with cisplatin-gemcitabine in Asian patients. Bevacizumab was well tolerated in this patient group. [ABSTRACT FROM AUTHOR]

To indirectly compare real-life clinical effectiveness of bevacizumab + cisplatin-based therapy from the Safety of Avastin in Lung (SAiL) phase IV clinical trial with published evidence from the phase III clinical trial for pemetrexed + cisplatin among East Asian patients with non-squamous metastatic or recurrent non-small cell lung cancer (NSCLC). Survival outcomes were compared between subgroups of East Asian patients receiving treatments of either bevacizumab + cisplatin-based chemotherapy or pemetrexed + cisplatin using a matching-adjusted indirect comparison approach. Patient-level data were used to derive a new group with similar characteristics compared to those reported in a phase III clinical trial evaluating pemetrexed + cisplatin therapy. Exclusions to the SAiL data included those with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2, those with mixed cell histology, non-East Asians and those who did not receive cisplatin-based chemotherapy. In total 1000 samples of the pre-matched analysis set of the SAiL data were selected that resulted in equal distributions of the ECOG PS and gender matching variables selected and evaluated for a progression-free survival (PFS) outcome. Median PFS was longer for patients treated with bevacizumab-based therapy (7.4 months; 95% confidence interval [CI]: 6.7-8.2) versus pemetrexed + cisplatin (6.4 months; 95% CI N/A) among non-squamous East Asian NSCLC patients. The results suggest that East Asian non-squamous NSCLC patients treated with bevacizumab-based therapy have a trend toward improved PFS outcomes compared to those treated with pemetrexed + cisplatin, even after adjusting for differences between the two trial groups. [ABSTRACT FROM AUTHOR]

The aim of this analysis is to investigate the mean incremental costs and life expectancy associated with two first-line treatments for advanced non-squamous non-small cell lung cancer (NSCLC) in Korea and Taiwan; bevacizumab plus cisplatin and gemcitabine (BevCG) and cisplatin plus pemetrexed (CP). A health economic (area under curve) model with three health states was developed to assess health outcomes (life-years gained [LYG]), direct costs, and incremental cost-effectiveness ratio (ICER). Progression-free survival (PFS) and overall survival (OS) were derived from randomized clinical trials and used in an indirect comparison in order to estimate their cost effectiveness. A life-time horizon was used. Costs and outcomes were discounted yearly by 5% in Korea and by 3% in Taiwan. The incremental LYG for the BevCG patients compared with patients treated with CP were 1.10 (13.2 months) in Korea and 1.19 (14.3 months) in Taiwan. The incremental costs were 37 439 968 ($33 322) in Korea and NT$1 910 615 ($64 541) in Taiwan. The incremental cost-effectiveness ratio was 34 064 835 ($30 318) in Korea and NT$1 607 960 ($54 317) in Taiwan. The inputs tested in one-way sensitivity analyses had very little impact on the overall cost effectiveness. This analysis shows that BevCG is more costly but is also associated with additional life-years in Korea and Taiwan. The ICER per LYG suggests that BevCG is a cost-effective therapy when compared to CP for patients with advanced NSCLC in Korea and Taiwan. [ABSTRACT FROM AUTHOR]

Adjuvant chemotherapy and hormonal therapy reduce the risk of recurrence and death due to breast cancer, but often at considerable cost to the health-related quality of life (HRQL) of patients. The short-term effects of chemotherapy on HRQL are well known and are accepted by most patients for modest gains in survival. The long-term effects of chemotherapy-induced menopause and hormonal therapy on HRQL are poorly recognized. Vasomotor symptoms and altered sexual function are common, distressing and inadequately treated. HRQL information is helpful in describing likely effects of adjuvant treatment, facilitating informed decision-making, identifying health problems to guide research into potential solutions, guiding treatment strategies for interventions with equivalent survival and guiding resource allocation. New technologies will make HRQL information increasingly available for individual patient care. [ABSTRACT FROM AUTHOR]

Purpose. The safety and efficacy of oral metronomic low-dose treosulfan chemotherapy in combination with the cyclooxygenase-2 (COX-2) inhibitor rofecoxib as a compound with antiangiogenic potential, a therapeutic regimen optimally targeting endothelial cells instead of tumor cells, were assessed in pretreated advanced melanoma patients. Methods. Endothelial cells were analyzed for proliferation, apoptosis and cytotoxicity in response to increasing concentrations of treosulfan, either in the absence or presence of COX-2 inhibitor, to determine whether inhibition of COX-2 enhanced the effect of treosulfan on cell function. In a clinical pilot study, 12 consecutive patients with pretreated advanced melanoma, meeting the eligibility criteria were enrolled. Patients received combined daily treosulfan chemotherapy (500 mg) with rofecoxib (25 mg). Metastatic lesions were assessed every 12 weeks. Patients with responsive or stable disease were eligible for a further 12-week treatment period. Response criteria according to the WHO handbook for reporting results of cancer treatment were applied. Side effects were classified according to the National Cancer Institute's Common Toxicity Criteria v2.0. Results. At noncytotoxic concentrations, treosulfan inhibited endothelial cell proliferation in a dose-dependent fashion. Simultaneous inhibition of COX-2 significantly increased the extent to which treosulfan suppressed cell proliferation, without inducing cytotoxicity. In the pilot study in which 12 patients were treated, toxicity was mild; only hematologic toxicity of grade II was seen. An objective response was noted in one patient, and four patients showed stabilization of their disease for 24 weeks (one) and 36 weeks (three). The patient who had a partial response subsequently showed stable disease for 48 weeks. The median survival time was 13 months. Conclusions. As increases in response rates following polychemo- or biochemotherapy have not been shown to correlate with prolongation in overall survival, more durable control of metastatic melanoma represents an attractive therapeutic goal. Thus, regimens scheduled to primarily target endothelial cells may potentially provide a palliative alternative that preserves quality of life in the absence of significant treatment-related toxicity. [ABSTRACT FROM AUTHOR]