Budget impact analysis of treatment-free remission in nilotinib-treated Japanese chronic myeloid leukemia patients.

Treatment-free remission (TFR), in which patients discontinue pharmacotherapy and remain in molecular remission, is an emerging treatment goal for patients with chronic myeloid leukemia (CML). Attainment of TFR requires an increased frequency of molecular monitoring, to ensure that patients maintain a deep molecular response. The objective of this analysis was to assess the economic impact of stopping nilotinib among Japanese TFR-eligible patients. A Markov model evaluated the economic impact of TFR among the study population, TFR-eligible CML patients diagnosed since 2012. The model compared patients who had discontinued tyrosine kinase inhibitor (TKI) treatment (ie, attempted TFR) with patients that continued TKI treatment. A 3-y time horizon was modeled from a Japanese public payer perspective. Costs associated with drug treatment, hospital/physician visits, and molecular monitoring were considered. TFR-eligible patients were calculated from Japanese CML incidence rates and efficacy was derived from nilotinib trials. Japanese co-payment maximums were utilized to assess the patient perspective. An estimated 761 and 140 patients were eligible for first- and second-line nilotinib, respectively, in 2019. Assuming that 100% of eligible patients complied, TFR was associated with cost savings of ¥7 625 174 640 (US$66 567 775) over 3 y. In scenarios with reduced willingness to attempt TFR, cost savings persisted. Achievement of TFR was estimated to markedly reduce out-of-pocket expenses for CML patients, regardless of the timing of relapse. Stopping nilotinib for TFR-eligible patients in Japan may result in significant cost savings to both payers and patients. Monitoring costs contributed little to overall annual costs and decreased over time.

Erlotinib for Japanese patients with activating EGFR mutation-positive non-small-cell lung cancer: combined analyses from two Phase II studies.

AIMS: We evaluated the efficacy and safety of erlotinib, and patient characteristics affecting progression-free survival (PFS), by analyzing data from two Phase II studies of first-line erlotinib in activating EGFR mutation-positive non-small-cell lung cancer. METHODS: Data were combined from patients who received first-line erlotinib monotherapy in JO22903 (single-arm study; JapicCTI-101085) and JO25567 (randomized study; JapicCTI-111390). RESULTS: Median PFS was 10.9 months in efficacy-evaluable patients (n = 177). Major adverse events were dermatologic; no new safety signals were observed. Baseline pleural/cardiac effusion notably affected PFS (yes median 8.0 months vs no median 15.3 months) as confirmed in multivariate analysis (hazard ratio: 0.38; 95% CI: 0.25-0.58). CONCLUSION: Efficacy and safety of erlotinib monotherapy were consistent with previous studies. Baseline pleural/pericardial effusion was associated with shorter PFS.

Increased Expression of the Genes for Mitotic Spindle Assembly and Chromosome Segregation in Both Lung and Pancreatic Carcinomas.

Genes whose expression was modulated in two different tumor types, lung or pancreatic carcinoma, were identified by DNA microarray and subsequent expression correlation analyses. For more accurate comparison of the gene expression between tumor and normal cells, tumor cells and normal epithelium cells were isolated by laser-captured microdissection. Genes whose expression was significantly altered in lung carcinomas or pancreatic carcinomas as compared to their normal counterparts were ranked by the T-values calculated from the Fisher's ratios and their corresponding background Fisher's ratios, followed by statistical confirmation using the Welch's t-test. Among the genes that were ranked in the top 150, either in lung carcinomas or pancreatic carcinomas, expressions of MAD2, BUB1, BUB1B, HEC, CENPE, ZWINT, KNSL1, SMC4, CCNB, TK and PMS2L6 were found to be significantly up-regulated in both tumor types. Interestingly, 8 of the above 11 genes code for the proteins involved in the mitotic spindle assembly and chromosome segregation. Furthermore, the search for genes whose expression correlated with one of the above 5 genes yielded additional genes that are also considered to be involved in mitotic spindle assembly and chromosome segregation. Thus, increased expression of the genes for mitotic spindle assembly and chromosome segregation are a common feature of at least lung carcinomas and pancreatic carcinomas and, therefore, such genes may be potential targets for widely effective anticancer agents.

The usefulness of immunohistochemical evaluation of dihydropyrimidine dehydrogenase for rectal cancer treated with preoperative radiotherapy.

BACKGROUND/AIMS: DPD (dihydropyrimidine dehydrogenase) activity shows a correlation with 5-fluorouracil chemosensitivity. To quantify DPD activity is important for selection of chemosensitive cases of not only sporadic colorectal cancer but also rectal cancer with preoperative radiotherapy. However, it is not cost-effective. We investigated the relation between the immunohistochemical expression pattern of DPD and its activity in rectal cancer treated with radiotherapy, and compared the immunohistochemical DPD expression pattern of preradiation biopsy specimens with that of resected tissues. METHODOLOGY: DPD expression pattern of preradiation biopsy specimens were compared with that of resected tissues. Eighteen colorectal cancer tissue samples were obtained after surgery from October 2000 to January 2001. DPD activity was quantified by sandwich enzyme-linked immunosorbent assay. The streptoavidin-biotin peroxidase complex technique was used for the immunohistochemical expression pattern. RESULTS: DPD was stained in the cytoplasm of cancer cells. There was a significant correlation between the immunohistochemical expression pattern of DPD and its activity in tumor tissue treated with or without radiotherapy. The immunohistochemical expression pattern of preradiation biopsy specimens was almost the same as that of resected tissues. CONCLUSIONS: The immunohistochemical expression pattern of DPD correlated with its activity in tumor tissue treated with preoperative radiotherapy. Immunohistochemical evaluation is considered to be an effective method of predicting the sensitivity to 5-fluorouracil of rectal cancer treated with preoperative radiotherapy.