• Journal of Digestive Cancer Research
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• v.2 no.2
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• pp.52-55
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• 2014

The incidence of colorectal cancer (CRC) has continuously increased and CRC is a major cause of cancer-related death. Systemic chemotherapy has resulted in a significant improvement in overall survival in metastatic CRC. The development of biologic agents for the treatment of CRC has additionally expanded the options for the treatment. Cetuximab is useful in KRAS wild type tumors in combination with chemotherapy for metastatic disease in both the first and second line settings. It is also used as monotherapy after failure of both irinotecan and oxaliplatin containing regimens. Panitumumab has similar indications, and is primarily used in patients intolerant to cetuximab due to hypersensitivity reactions. Bevacizumab is primarily used as first line and second line therapy in metastatic CRC. However, the optimal way and duration to combine these chemotherapeutic agents are not yet established.

• Journal of Digestive Cancer Research
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• v.6 no.1
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• pp.25-31
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• 2018

Background: In Korea, stomach cancer is the second most common malignancy and the third leading cause of cancer-related deaths. the time of diagnosis is very important for treatment so early detection and surgery are currently considered the mainstay of treatment, when diagnosed advanced with tumor extension through the gastric wall and direct extension into other organs, with metastatic involvement. Recently, new drugs, drug combinations, and multimodal approaches have been used to treat this disease and In cancers over expressing or amplifying HER2, the combination of cisplatin-fluoropyrimidine-trastuzumab is considered to be the treatment of reference. but At present, the choice of treatment schedule for HER2-negative tumors is based on the medical institution's preferences and adverse effects profile. The aim of this study was to evaluate the effectiveness and safety of using FOLFOX regimen as a first-line therapy or a salvage therapy in the patients with HER2-negative advanced or metastatic gastric cancer. Methods: We retrospective reviewed the patient medical record from March 2012 to July 2017. This study evaluated 113 patients. Sixty-eight patients were treated with the FOLFOX regimen for the first time (first-line group) and 45 patients were treated with the FOLFOX regimen as a second (35 patients) or third (10 patients) chemotherapy (salvage group). Results: In the first-line group, the response rate was 54.9%. In the salvage therapy group, the response rate was 24.4% and The difference was statistically significant (p=0.205). The median TTP of the first-line group was 10.7 months (95% confidence interval [95% CI], 7.8-13.7 months) and that of salvage line group was 6.1 months (95% CI, 3.8-8.4 months). The median OS of the first-line group was 15.8 months (95% CI, 12.7-18.9 months) and that of the salvage therapy group was 10.2 months (95% CI, 8.2-11.9 months). drug toxicity was similar andtolerable between two groups. Conclusion: In patients with unresctable metastatic gastric cancer, after failing to respond to first-line therapy, most patients have no alternative other than second-line therapy because the disease is highly progressive. if the performance status of the patient is good enough to be eligible to treatments beyond best supportive care. FOLFOX regimen can be a considerable therapeutic option for salvage treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7119-7123
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• 2014

Background: The role of second-line therapy in metastatic pancreatic cancer is not clear. In this study, we aimed to explore the second-line efficiency of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer who have received gemcitabine-based first-line therapy. Materials and Methods: We retrospectively evaluated 47 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine-based first-line regimens. Treatment consisted of oxaliplatin $130mg/m^2$ and capecitabine $1000mg/m^2$ twice daily with a 3 week interval, until unacceptable toxicity or disease progression. Results: Median number of cycles was 4 (range, 2-10). The overall disease control rate was 38.3%. The median overall survival and progression-free survival from the start of second-line therapy were 23 weeks (95%CI: 16.6-29.5 weeks) and 12 weeks (95%CI: 9.8-14.4 weeks), respectively. The most common grade 3-4 toxicities were nausea, vomiting and hematologic side effects. Conclusions: Our result suggests that the combination of capecitabine and oxaliplatin was tolerated with manageable toxicity and showed encouraging activity as second-line treatment of advanced or metastatic pancreatic cancer patients with ECOG performance status 0-2.

• Journal of Yeungnam Medical Science
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• v.40 no.3
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• pp.241-246
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• 2023

Immune thrombocytopenia (ITP) is a disease in which thrombocytopenia occurs because of immune-mediated platelet destruction and decreased platelet production. Although many pediatric patients with ITP experience spontaneous remission or reach remission within 12 months of first-line therapy, approximately 20% progress to chronic ITP. Patients who do not respond to first-line treatment or experience frequent relapses are of great concern to physicians. This review summarizes recent treatments for second-line treatment of pediatric chronic ITP.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6359-6364
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• 2015

Background: Preclinical studies have shown that the combination of an aromatase inhibitor (AI) and capecitabine in estrogen receptor (ER)- positive cell lines enhance antitumor efficacy. This retrospective analysis of a group of patients with metastatic breast cancer (MBC) evaluated the efficacy and safety of combined AI with capecitabine. Materials and Methods: Patients with hormone receptor-positive metastatic breast cancer treated between 1st January 2005 and 31st December 2010 with a combination of capecitabine and AI were evaluated and outcomes were compared with those of women treated with capecitabine in conventional dose or AI as a monotherapy. Results: Of 72 patients evaluated, 31 received the combination treatment, 22 AI and 19 capecitabine. The combination was used in 20 patients as first-line and 11 as second-line treatment. Mean age was 46.2 years with a range of 28-72 years. At the time of progression, 97% had a performance status of <2 and 55% had visceral disease. No significant difference was observed between the three groups according to clinical and pathological features. Mean follow up was 38 months with a range of 16-66 months. The median PFS of first-line treatment was significantly better for the combination (PFS 21 months vs 8.0 months for capecitabine and 15.0 months for AI). For second-line treatment, the PFS was longer in the combination compared with capecitabine and Al groups (18 months vs. 5.0 months vs. 11.0 months, respectively). Median 2 year and 5 year survival did not show any significant differences among combination and monotherapy groups. The most common adverse events for the combination group were grade 1 and 2 hand-for syndrome (69%), grade 1 fatigue (64%) and grade 1 diarrhoea (29%). Three grade 3 hand-foot syndrome events were reported. Conclusions: Combination treatment with capecitabine and AI used as a first line or second line treatment was safe with much lowered toxicity. Prospective randomized clinical trials should evaluate the use of combination therapy in advanced breast cancer to confirm these findings.

• Journal of Gastric Cancer
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• v.23 no.1
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• pp.224-249
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• 2023

Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

• Tuberculosis and Respiratory Diseases
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• v.67 no.3
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• pp.191-198
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• 2009

Background: Pemetrexed, a multi-targeted antifolate has been used as a second line treatment against non-small cell lung cancer (NSCLC). We aimed to clarify the efficacy and survival according to line of treatment, histologic type, and expression of thymidylate synthase (TS). Methods: Ninety-eight patients were treated with pemetrexed as a second line treatment (n=43) or as an additional course of treatment (n=55). TS expression was studied with immunohistochemistry and graded as 0 to 3 based on the extent of expression. Results: The response rate (RR) in 98 subjects was 10.2% and the disease control rate (DCR=PR+SD) was 30.6%. RR and DCR were 12.7% and 32.7% in non-squamous cell carcinoma (NSQC) compared to 7.0% and 27.9% in squamous cell carcinoma (SQC) (p>.05). No significant differences in RR and DCR were observed between a second line group (4.7%, 20.9%) and a further line group (14.5%, 38.2%). A similar trend was observed in the 88 response evaluable subjects. TS was expressed in 28.6% (grade 1), 24.5% (grade 2) and 7.1% (grade 3), respectively, and it was not expressed in 39.8% of subjects. TS expression rate was significantly higher in the SQC (72.1%) compared to NSQC (50.9%, p=0.033). However, the efficacy of pemetrexed was not significantly different by the extent of TS expression. Conclusion: Pemetrexed showed efficacy, not only in a second-line setting, but also in further lines of treatment for NSCLC. The efficacy of pemetrexed tended to be higher in patients with NSQC compared to SQC. TS expression rate was significantly higher in SQC compared to NSQC.

• Journal of Yeungnam Medical Science
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• v.37 no.4
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• pp.277-285
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• 2020

Tuberculosis (TB) is still a major health problem worldwide. Especially, multidrug-resistant TB (MDR-TB), which is defined as TB that shows resistance to both isoniazid and rifampicin, is a barrier in the treatment of TB. Globally, approximately 3.4% of new TB patients and 20% of the patients with a history of previous treatment for TB were diagnosed with MDR-TB. The treatment of MDR-TB requires medications for a long duration (up to 20-24 months) with less effective and toxic second-line drugs and has unfavorable outcomes. However, treatment outcomes are expected to improve due to the introduction of a new agent (bedaquiline), repurposed drugs (linezolid, clofazimine, and cycloserine), and technological advancement in rapid drug sensitivity testing. The World Health Organization (WHO) released a rapid communication in 2018, followed by consolidated guidelines for the treatment of MDR-TB in 2019 based on clinical trials and an individual patient data meta-analysis. In these guidelines, the WHO suggested reclassification of second-line anti-TB drugs and recommended oral treatment regimens that included the new and repurposed agents. The aims of this article are to review the treatment strategies of MDR-TB based on the 2019 WHO guidelines regarding the management of MDR-TB and the diagnostic techniques for detecting resistance, including phenotypic and molecular drug sensitivity tests.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.799-805
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• 2016

Background: There is no standard treatment for patients with platinum-resistant or refractory epithelial ovarian cancer. Single agent chemotherapies have evidence of more efficacy and less toxicity than combination therapy. Most are very expensive, with appreciable toxicity and minimal survival. Since it is difficult to make comparison between outcomes, economic analysis of single-agent chemotherapy regimens and best supportive care may help to make decisions about an appropriate management for the affected patients. Objective: To evaluate the cost effectiveness of second-line chemotherapy compared with best supportive care for patients with platinum-resistant or refractory epithelial ovarian cancer. Materials and Methods: A Markov model was used to estimate the effectiveness and total costs associated with treatments. The hypothetical patient population comprised women aged 55 with platinum-resistant or refractory epithelial ovarian cancer. Four types of alternative treatment options were evaluated: 1) gemcitabine followed by BSC; 2) pegylated liposomal doxorubicin (PLD) followed by BSC; 3) gemcitabine followed by topotecan; and 4) PLD followed by topotecan. Baseline comparator of alternative treatments was BSC. Time horizon of the analysis was 2 years. Health care provider perspective and 3% discount rate were used to determine the costs of medical treatment in this study. Quality-adjusted life-years (QALY) were used to measure the treatment effectiveness. Treatment effectiveness data were derived from the literature. Costs were calculated from unit cost treatment of epithelial ovarian cancer patients at various stages of disease in King Chulalongkorn Memorial Hospital (KCMH) in the year 2011. Parameter uncertainty was tested in probabilistic sensitivity analysis by using Monte Carlo simulation. One-way sensitivity analysis was used to explore each variable's impact on the uncertainty of the results. Results: Approximated life expectancy of best supportive care was 0.182 years and its total cost was 26,862 Baht. All four alternative treatments increased life expectancy. Life expectancy of gemcitabine followed by BSC, PLD followed by BSC, gemcitabine followed by topotecan and PLD followed by topotecan was 0.510, 0.513, 0.566, and 0.570 years, respectively. The total cost of gemcitabine followed by BSC, PLD followed by BSC, gemcitabine followed by topotecan and PLD followed by topotecan was 113,000, 124,302, 139,788 and 151,135 Baht, respectively. PLD followed by topotecan had the highest expected quality-adjusted life-years but was the most expensive of all the above strategies. The incremental cost-effectiveness ratios (ICER) of gemcitabine followed by BSC, PLD followed by BSC, gemcitabine followed by topotecan and PLD followed by topotecan was 344,643, 385,322, 385,856, and 420,299 Baht, respectively. Conclusions: All of the second-line chemotherapy strategies showed certain benefits due to an increased life-year gained compared with best supportive care. Moreover, gemcitabine as second-line chemotherapy followed by best supportive care in progressive disease case was likely to be more effective strategy with less cost from health care provider perspective. Gemcitabine was the most cost-effective treatment among all four alternative treatments. ICER is only an economic factor. Treatment decisions should be based on the patient benefit.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6799-6804
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• 2014

Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Second-line chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai Pulmonary Hospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker (HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following second-line chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.