• Korean Journal of Clinical Pharmacy
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• v.21 no.3
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• pp.193-207
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• 2011

Purpose: The purpose of this study is to assess appropriateness of current standard for insurance coverage by Health Insurance Review & Assessment Service (HIRA) on chemotherapy used in the treatment of advanced non-small cell lung cancer (NSCLC), by reviewing a variety of clinical evidences, and thereby, if needed, to propose an updated evidence-based recommendations. Methods: We collected data from HIRA regarding on the insurance standard which includes the scope and conditions for coverage on systemic chemotherapy of NSCLC. We performed a search for clinical databases and examined the most current clinical evidence from clinical literature including various clinical practice guidelines. Based on the collected data the appropriateness of HIRA standard for insurance coverage of chemotherapy of NSCLC was assessed. Results: Collected data demonstrated that HIRA standard did not reflect the most current clinical practice and evidence. Some were inappropriately listed in HIRA formulary and accepted as a chemotherapy being covered by insurance, despite the lack of evidences of clinical efficacy or superiority over other chemotherapeutic agents or regimens. In addition, there seems to be a need for a modification on the standard for insurance coverage of certain newer chemotherapeutic agents based on the current accumulated data showing their clinical efficacy and benefits in the selected group of NSCLC patients. Therefore, we concluded that current HIRA standard for insurance coverage on chemotherapy of NSCLC needs to be revised and we proposed an updated recommendation based on these latest clinical evidences. Conclusion: The standard for insurance coverage of chemotherapy should be continually examined its appropriateness based on the most recent clinical evidences in a timely manner so as to provide the most effective and safe therapy to cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8591-8594
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• 2014

Background: Lung cancer is the most common cancer in males worldwide. The principal mode of treatment in the early stage of non-small cell lung cancer (NSCLC) is surgery. However, five-year survival is only about 15% for all stages. The aim is to investigate the effect of daily low dose cisplatin concurrently with radiation therapy in advanced NSCLC patients with poor performance status. Materials and Methods: Ten patients diagnosed as inoperable Stage IIIB NSCLC with comorbid disease were assessed retrospectively in Bezmialem Vakif University, Faculty of Medicine, Department of Radiation Oncology, between 2011 to 2013. ECOG performance status was between 3 and 4. Cisplatin was administered at $6mg/m^2$ daily, for 5 days a week concurrently with radiotherapy using 160-200 cGy daily fractions, 54 Gy being the lowest and 63 Gy being the highest dose. Results: Complete response at the primary tumour site was obtained in 20% patients. Grade I esophagitis was seen 70 percent of patients, and the grade II haematological toxicity rate was 20 %. Median survival time was 7 months. Conclusions: Median survival time was reasonable, despite the patients ECOG performance status of 3-4, which is similar to groups even without comorbid disorders in comparison to other published papers in the literature. Acceptable toxicity, high response rates and quality of life of patients are the other favourable features.

• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.76-83
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• 1995

Background: Despite advances in chemotherapy, the treatment of inoperable non-small cell carcinoma of the lung remains poor. According to the recent reports, the response rates of mitomycin, vinblastine, and cisplatin(MVP) chemotherapy are higher than those of other cisplatin based polychemotherapy and MVP chemotherapy can be used as neoadjuvant chemotherapeutic regimen. But the overall response rates of MVP chemotherapy range from 17 to 53 percent, so we studied the effect of MVP chemotherapy in advanced non-small cell lung cancer. Method: We treated forty patients with stage III or IV non-small cell lung cancer with two courses of MVP chemotherapy($8mg/m^2$ of mitomycin on day 1, $6mg/m^2$ of vinblastine on day 2 & day 14, and $100mg/m^2$ of cisplastin on day 1) at 4 weeks interval. Then all patients were evaluated the response of chemotherapy 4 weeks later, and received further chemotherapy, palliative radiotherapy or supportive therapy according to the patient's condition. We also determined the median survival time and prognostic factors. Results: 1) Nine patients(23%) had a partial reponse, 23 patients(57%) had a stable disease, and disease progressed in 8 patients(20%). There were no patients with complete response. 2) The overall median survival time was 36 weeks(range, 9 to 119+ weeks). The median survival time of responder(partial response) and non-responder(stable and progressed) groups were 60 weeks(range, 36 to 82+ weeks) and 31 weeks(range, 9 to 119+ weeks) respectively(p=0.03). 3) The median survival time of the female group was 71 weeks and significantly prolonged in comparision with 35 weeks of the male group(p=0.01). But, the other prognostic factors didn't affect the survival time and response rate. 4) The median survival times of chemotherapy group and chemotherapy with palliative radiotherapy group were not significantly different. Conclusion: MVP combined chemotherapy is unsatisfactory in improving survival in advanced non-small cell lung cancer. Therefore, further studies are needed to find more active new agents and to estabilish the efficacy of the combined treatment with radiotherapy and/or surgery.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5177-5182
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• 2012

Purpose: To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitormonotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agent docetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC). Methods: We systematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standard second-line chemotherapy in previously treated advanced NSCLC. The end points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), 1-year survival rate (1-year SR) and grade 3 or 4 toxicities. The pooled hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis results showed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC in terms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI 0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall response rate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysis demonstrated that EGFR-TKI monotherapy significantly improved PFS (HR 0.73, 95%CI: 0.55-0.97, p=0.03) and ORR (RR 1.96, 95%CI: 1.46-2.63, p=0.000) in East Asian patients, but it did not translate into increase in OS and 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia and neutrotoxicity in EGFR-TKI monotherapy group, excluding grade 3 or 4 rash. Conclusion: Both interventions had comparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapy was associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFR-TKImonotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with standard second-line chemotherapy. These results should help inform decisions about patient management and design of future trials.

• Tuberculosis and Respiratory Diseases
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• v.76 no.1
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• pp.1-7
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• 2014

Maintenance therapy has emerged as a novel therapeutic paradigm for advanced non-small-cell lung cancer (NSCLC). Maintenance therapy that aims to sustain a clinically favorable state after first-line chemotherapy has two strategies. Switch maintenance therapy entails switching to a new and non-cross-resistant agent in an alternating or sequential manner, on completion of first-line chemotherapy. Continuous maintenance therapy keeps ongoing administration of a component of the current regimen after four to six cycles of chemotherapy, if there is a stable disease, or better response. Both maintenance therapies can be continued, until disease progression. The potential evidence regarding maintenance therapy includes providing the opportunity to receive additional treatment, through sustaining tumor shrinkage, and delayed emergence of tumor-related symptom. Thus far, debates over the parameters used to predict the effectiveness of maintenance therapy, financial burden, and uncertainty of improving the quality of life exist. Despite many debates, maintenance therapy, which is currently recommended, has been disclosed to be beneficial.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.775-780
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• 2012

8-isoprostane (8-$isoPGF_{2{\alpha}}$) is a reliable marker and considered a gold standard for lipid peroxidation. There are very few reports of 8-isoprostane levels in cancer patients, and in patients undergoing chemotherapy. Oxidative stress is however expected and has been observed in patients with cancer. This study measured 8-isoprostane levels in urine by ELISA of 25 patients undergoing chemotherapy for advanced non-small cell lung cancer, at cycles 1, 2, and 3 of treatment. It considers the creatinine clearance of the patients, and correction of 8-isoprostane levels by creatinine clearance, and overnight urine volume methods. The average 8-isoprostane levels in urine increased more than 6 to 12 fold on chemotherapy treatment, from $532{\pm}587$ pg/mL at cycle $1,6181{\pm}4334$ at cycle 2, and $5511{\pm}2055$ at cycle 3. Similar results were obtained if 8-isoprostane levels were corrected for overnight urine volume, giving averages of $285{\pm}244{\mu}g$ at cycle $1,4122{\pm}3349$ at cycle 2, and $3266{\pm}1200$ at cycle 3. No significant difference was seen in average total overnight urine volume or number of urinations between chemotherapy cycles except for a large variation in urine volume between cycle 2 and 3. Creatinine levels were significantly different only between cycles 1 and 2 (p=0.016). In conclusion, cisplatin therapy has been shown to induce high levels of lipid peroxidation in lung cancer patients and can be assessed from the 8-isoprostane marker in overnight urine, with or without urine volume correction.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.536-546
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• 1996

Background : The survival benefit of combination chemotherapy comparing supportive care to patients with advanced non-small cell lung cancel, especially stage IV non-small cell lung cancer patients with metastatic disease, is controversial. The main goal of this study was to evaluate the difference in survival between patients treated with chemotherapy and those who were not and to identify prognostic factors in the patients with stage IV non-small cell lung cancer. Methods : From January 1989 to December 1994, total 67 patients including 20 patients treated with combination chemotherapy and 47 patients treated with only supportive care in stage IV non-small cell lung cancer patients with metastatic disease were enrolled in this study. Combination chemotherapy consisted of etoposide $120mg/m^2$ iv for 3 days and cis-platin iv day 1 every 4 weeks. The treatment groups were retrospectively analyzed by age, sex, histologic cell type, weight loss, serum LDH level, ECOG performance status and major organ metastasis. Results : The significant prognostic factors influencing survival on this study were ECOG performance status and histologic subtype. Overall response rate by combination chemotherapy was 30%(complete response 0%, partial response 30%). Median survival of overall patients was 13.6 weeks and median survival of Chemotherapy group, 20 weeks, was significantly longer than that of supportive care group, 11.7 week(p<0.01). Median survival of responded in patients receiving chemotherapy, 45.5 weeks, was significantly longer than that of non-responder, 17.3 weeks(p<0.05). 1 year-survival rate of chemotherapy group and supportive care group was 15N and 8%, respectively. Nausea or vomiting, alopecia and anemia were seen in nearly most cases after this combination chemotherapy. Toxicities above grade 3 included neutropenia, anemia, thrombocytopenia, infection, fever, nausea, vomiting and alopecia. But this combination chemotherapy was relatively well tolerated except one treatment-related death from sepsis associated with severe granulocytopenia. Conclusion : These results suggest that systemic chemotherapy might be helpful to the stage IV non-small cell lung cancer patients with good performance status and large scale randomized prospective trials should be performed.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1837-1840
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• 2012

Background: In spite of the fact that platinum-based doublets are considered the standard therapy for patients with advanced non-small-cell lung cancer (NSCLC), no elderly-specific platinum based prospective phase III regimen has been explored. The aim of this retrospective singlecenter study was to evaluate the efficacy and side effects of cisplatin-based therapy specifically for the elderly. Methods: Patients receiving platinum-based treatment were divided into three groups. In the first group (GC), Gemcitabine was administrated at 1000 $mg/m^2$ on days 1, 8 and cisplatin was added at 75 $mg/m^2$ on day 1. In the second group (DC), 75 $mg/m^2$ docetaxel and cisplatin were administered on day 1. The third group (PC) received 175 mg of paclitaxel and 75 mg of cisplatin on day 1. These treatments were repeated every three weeks. Result: GC arm had 36, the DC arm 42 and the PC arm 29 patients. Grade III-IV thrombocytopenia was higher in the GC arm (21.2% received GC, 2.8% received DC, and 3.8% received PC), while sensory neuropathy was lower in patients with GC arm (3.0%, 22.2%, and 23.1% received GC, DC and PC, respectively). There were no statistically significant difference in the response rates among the three groups (p>0.05). The median Progression-free survival (PFS) was 5.0 months and the median Overall survival (OS) in each group was 7.1, 7.4 and 7.1 months, respectively (p>0.05). Conclusion: The response rate, median PFS and OS were similar among the three treatment arms. Grade III-IV thrombocytopenia was higher in the GC arm, while the GC regimen was more favorable than the other cisplatin-based treatmetns with regard to sensory neuropathy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.29-32
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• 2014

Background and Objective: Lung cancer is one of the malignant diseases which most seriously threat humansurvival and development. This study aimed to assess osteopontin (OPN) expression in non-small cell lung cancer (NSCLC) and any relationship with clinicopathological features. Methods: Immunohistochemistry was used to determine OPN expression and microvascular density (MVD) in 120 cases of NSCLC also undergoing clinical assessment. Results: Moderately positive expression of OPN was found in 34.6% (41/120) and strong expression in 47.5% (57/120) of the NSCLCs; OPN expression in carcinomas was higher than in pericarcinoma tissues (P<0.05). While no obvious association was observed with NSCLC patient age, gender, maximum diameter of the tumor and pathological type, OPN expression was more commonly detected in poorly differentiated carcinoma tissue and lymph node metastasis as well as at advanced clinical stage (P<0.05); OPN expression in cancer tissue was positively correlated with MVD (r = 0.839, P = 0.000). Conclusion: OPN plays an important role in promoting tumor angiogenesis and progress of NSCLCs and has the possibility to become the new target for therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5119-5124
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• 2012

Purpose: The aim of this retrospective study was to determine response rates, progression-free survival (PFS), overall survival (OS) and toxicity of gemcitabine and paclitaxel combinations with advanced or metastatic non-small cell lung cancer patients (NSCLC) who have progressive disease after platinum-based first-line chemotherapy. Methods: We retrospectively evaluated the file records of patients treated with gemcitabine plus paclitaxel in advanced or metastatic NSCLC cases in a second-line setting. The chemotherapy schedule was as follows: gemcitabine $1500mg/m^2$ and paclitaxel 150 mg/m2 administered every two weeks. Results: Forty-eight patients (45 male, 3 female) were evaluated; stage IIIB/IV 6/42; PS0, 8.3%, PS1, 72.9%, PS2, 18.8%; median age, 56 years old (range 38-76). Six (12.5%) patients showed a partial response (PR), 13 (27.1%) stable disease (SD), and 27 (56.3%) progressive disease (PD). The median OS was 6.63 months (95% CI 4.0-9.2); the median PFS was 2.7 months (95% CI 1.8-3.6). Grade 3 and 4 hematologic toxicities, including neutropenia (n=4, 8.4%), and anemia (n=3, 6.3%) were encountered, but no grade 3 or 4 thrombocytopenia. One patient developed febrile neutropenia. There were no interruption for reasons of toxicity and no exitus related to therapy. Conclusion: The combination of two-weekly gemcitabine plus paclitaxel was an effective and well-tolerated second-line chemotherapy regimen for advanced or metastatic NSCLC patients previously treated with platinum-containing chemotherapy. Although the most common and dose limiting toxicities were neutropenia and neuropathy, this regimen was tolerated well by the patients.