• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4127-4131
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• 2015

Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib. Materials and Methods: Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. Results: The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. Conclusions: Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.

• Journal of Veterinary Clinics
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• v.30 no.5
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• pp.363-365
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• 2013

A 15-year-old, spayed female Maltese dog weighing 2.80 kg was referred with seizure of unknown origin. At presentation, serum biochemistry showed marked hypoglycemia (46 mg/dL; reference interval [RI], 65-118 mg/dL). There were, however, no abnormalities on electrolytes, complete blood counts, urinalysis, survey radiographs, and abdominal ultrasonography. In the adrenocorticotropic hormone (ACTH) stimulation test, pre-ACTH and post-ACTH cortisol concentrations were within normal reference ranges. Serum insulin level was normal and fructosamine level was slightly lower than reference ranges. The clinical signs, including seizure and collapse caused by hypoglycemia, were gradually resolved with oral administration of prednisolone (PDS) twice daily. Forty five weeks later, serum biochemistry revealed hypoglycemia with markedly increased insulin level. On abdominal ultrasonography, increased heterogenous echogenecity with hypoechoic lesion was found within pancreatic parenchyma. Based on these findings, the dog was presumptively diagnosed to insulinoma. Hypoglycemic seizure was resolved with higher dose of PDS (1 mg/kg, q12h). At 688 days after first presentation, the patient was still alive without recurrence of hypoglycemic seizure. This case describes long-term management with PDS monotherapy in a Maltese dog with insulinoma.

• Tuberculosis and Respiratory Diseases
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• v.61 no.2
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• pp.143-149
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• 2006

Background: Irinotecan (topoisomerase I inhibitor) is effective as a monotherapy against small-cell lung cancer(SCLC). Cisplatin is also an important drug against SCLC. A phase II study of irinotecan combined with cisplatin was carried out to evaluate the efficacy and toxicity of this combined regimen as a first line treatment in patients with extensive SCLC. Methods: Thirty-nine patients with previously untreated extensive SCLC were enrolled in this study. Irinotecan $60mg/m^2$ was administered intravenously on days 1, 8 and 15, and in combination with cisplatin $60mg/m^2$ on day 1 and every 28 days thereafter. Four cycles of chemotherapy were given to the patients. Results: The overall response rate was 77% with a complete response (CR) rate of 8%. The median survival time, 1- and 2-year survival rate were 14.8 months, 60.9% and 27.6%, respectively. The median progression free survival time, 6-and 12-month progression free survival rate were 8.4 months, 75% and 18.8%, respectively. The WHO grade 3 or more toxicity encountered were leukopenia (23%), diarrhea (26%). Two patients changed their chemotherapeutic regimen and one patient died from severe diarrhea. Conclusion: The combination of irinotecan and cisplatin is effective as a first line therapy in extensive SCLC is effective, but has severe or fatal diarrhea as toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.813-818
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• 2014

Aims: To describe our institutional experience with high dose rate (HDR) interstitial brachytherapy (IBT) compared with previously reported results on the low dose rate (LDR) practice for head and neck cancer. Materials and Methods: Eighty-four patients with oral cavity (n=70) or oropharyngeal cancer (n=14) were treated with 192Ir HDR-IBT. Seventy-eight patients had stage I or II tumour. The patients treated with IBT alone (n=42) received 39-42 Gy/10-14 fractions (median=40 Gy/10 fractions). With respect to the combination therapy group (n=42), prescription dose comprised of 12-18 Gy/3-6 fractions (median=15 Gy/5 fractions) for IBT and 40-50 Gy/20-25 fractions (median=50 Gy/25 fractions) for external radiotherapy. Brachytherapy was given as 2 fractions per day 6 hours apart with 4 Gy per fraction for monotherapy and 3 Gy per fraction for combination therapy. Results: Four patients were not evaluable in the analysis of outcome. The primary site relapse rates were 23.8% (10/42) and 68.4% (26/38) in patients treated with IBT alone and combination therapy, respectively (p<0.001). Salvage surgery was performed in 19 patients. The 5-year local control rate was estimated at 62% and the disease-free survival (DFS) rate at 52% for all patients. Local control with respect to T1 and T2 tumours was 84% and 42%, respectively. Conclusions: Our present series on HDR-IBT and the previous report on LDR-IBT for head and neck cancer demonstrated similar DFS rates at 5 years (52%). The rate of regional failure in node-negative patients was <20% in both of our series. HDR-IBT offers similar results to LDR-IBT for head and neck cancer.

• Clinical and Experimental Pediatrics
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• v.60 no.7
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• pp.227-231
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• 2017

Purpose: This study aimed to verify the safety of low-dose topiramate on language development in pediatric patients with migraine. Methods: Thirty newly diagnosed pediatric patients with migraine who needed topiramate were enrolled and assessed twice with standard language tests, including the Test of Language Problem Solving Abilities (TOPs), Receptive and Expressive Vocabulary Test, Urimal Test of Articulation and Phonology, and computerized speech laboratory analysis. Data were collected before treatment, and topiramate as monotherapy was sustained for at least 3 months. The mean follow-up period was $4.3{\pm}2.7months$. The mean topiramate dosage was 0.9 mg/kg/day. Results: The patient's mean age was $144.1{\pm}42.3months$ (male-to-female ratio, 9:21). The values of all the language parameters of the TOPs were not changed significantly after the topiramate treatment as follows: Determine cause, from $15.0{\pm}4.4$ to $15.4{\pm}4.8$ (P>0.05); making inference, from $17.6{\pm}5.6$ to $17.5{\pm}6.6$ (P>0.05); predicting, from $11.5{\pm}4.5$ to $12.3{\pm}4.0$ (P>0.05); and total TOPs score, from $44.1{\pm}13.4$ to $45.3{\pm}13.6$ (P>0.05). The total mean length of utterance in words during the test decreased from $44.1{\pm}13.4$ to $45.3{\pm}13.6$ (P<0.05). The Receptive and Expressive Vocabulary Test results decreased from $97.7{\pm}22.1$ to $96.3{\pm}19.9months$, and from $81.8{\pm}23.4$ to $82.3{\pm}25.4months$, respectively (P>0.05). In the articulation and phonology validation in both groups, speech pitch and energy were not significant, and all the vowel test results showed no other significant values. Conclusion: No significant difference was found in the language-speaking ability between the patients; however, the number of vocabularies used decreased. Therefore, topiramate should be used cautiously for children with migraine.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5527-5531
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• 2013

Background and Aim: Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic significance of the blood neutrophil-to-lymphocyte ratio (NLR) in patients with advanced HCC who received sorafenib monotherapy. Methods: A total of sixty-five patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib were enrolled. Potential prognostic factors such as age, gender, tumoral characteristics, performance status and NLR were analyzed. Results: Median OS and TTP for the entire cohort were 10.0 months (95%CI, 7.6-12.3 months) and 4.5 months (95% CI, 4.0-4.9 months). The mean NLR at baseline was 2.89. The median OS of patients with a high NLR (>4) was 6.5 months (95%CI, 5.2-7.7 months) compared with 12.5 months (95%CI, 9.9-15.0) for patients with a normal NLR (${\leq}4$) (P=0.01). Age ${\leq}65$, NLR>4, extrahepatic metastases and vascular invasion were all predictors of poorer overall survival. Multivariate analysis showed that NLR > 4, vascular invasion and extrahepatic metastases were independent predictors of poorer overall survival. The median TTP of patients with a high NLR was 2.5 months (95%CI, 1.4-3.6 months) compared with 4.5 months (95%CI, 3.9-5.1 months) for patients with a normal NLR (P=0.012). Conclusions: High baseline NLR was associated with worse OS and TTP for patients with advanced HCC treated with sorafenib.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.13 no.1
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• pp.44-50
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• 2010

Purpose: To estimate the viral suppressive effect of entecavir monotherapy in Korean children and adolescents with lamivudine-resistant chronic hepatitis B (CHB). Methods: One milligram of entecavir was administered once daily to 6 patients (4 boys; mean age, 17.5 years; range, 15.10~24.6 years) with lamivudine-resistant CHB for a mean duration of therapy of 13.4 months (range, 1~21.1 months). The therapeutic results were compared with 11 patients who received adefovir (0.3 mg/kg/day [maximal dose 10 mg]) for at least 12 months (mean, 33.4 months; range, 12.4~58.3 months). The serum HBV DNA level and serologic markers were measured every 2 months. Results: The interval to a HBV DNA titer decrement (>1 $log_{10}$) was 1.2${\pm}$0.2 and 4.4${\pm}$5.2 months (p=0.185) for the entecavir and adefovir groups, respectively. The interval to a HBV DNA titer decrement (>2 $log_{10}$) was 2.4${\pm}$2.3 and 9.2${\pm}$7.3 months (p=0.025), for the entecavir and adefovir groups, respectively. Conclusion: The therapeutic efficacy of entecavir was favorable in children and adolescents, especially in shortening the interval to a >2 $log_{10}$ decrement in the HBV DNA titer. Long-term follow up is needed to determine the therapeutic efficacy of entecavir for lamivudine-resistant CHB in children and adolescents.

• Tuberculosis and Respiratory Diseases
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• v.69 no.2
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• pp.115-118
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• 2010

Paclitaxel has been widely used for treating many solid tumors. Although colonic toxicity is an unusual complication of paclitaxel-based chemotherapy, the reported toxicities include pseudomembranous colitis, neutropenic enterocolitis and on rare occasions ischemic colitis. $Genexol-PM^{(R)}$, which is a recently developed cremophor-free, polymeric micelle-formulated paclitaxel, has shown a more potent antitumor effect because it can increase the usual dose of paclitaxel due to that $Genexol-PM^{(R)}$ does not include the toxic cremophor compound. We report here on a case of a 57-year-old man with advanced non-small cell lung cancer and who developed ischemic colitis after chemotherapy with $Genexol-PM^{(R)}$ and cisplatin. He complained of hematochezia with abdominal pain on the left lower quadrant. Colonoscopy revealed diffuse mucosal hemorrhage and edema from the sigmoid colon to the splenic flexure. After bowel rest, he recovered from his symptoms and the follow-up colonoscopic findings showed that the mucosa was healing. Since then, he was treated with pemetrexed monotherapy instead of a paclitaxel compound and platinum.

• Journal of Life Science
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• v.29 no.7
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• pp.824-835
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• 2019

In recent decades, oncolytic viruses (OVs) have extensively been investigated as a potential cancer drug. Oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Secondary, oncolytic viruses induce the activation of specific adaptive immunity which targets tumor-associated antigens that were hidden during the initial cancer progression. In 2015, one genetically modified oncolytic virus, talimogene laherparepvec (T-VEC), was approved by the American Food and Drug Administration (FDA) for the treatment of melanoma. Currently, various oncolytic viruses are being investigated in clinical trials as monotherapy or in combination with preexistent cancer therapies like immunotherapy, radiotherapy or chemotherapy. The efficacy of oncolytic virotherapy relies on the balance between the induced anti-tumor immunity and the anti-viral response. Despite the revolutionary outcome, the development of oncolytic viruses for the treatment of cancer faces a number of obstacles such as delivery method, neutralizing antibodies and induction of antiviral immunity due to the complexity, variability and reactivity of tumors. Intratumoral administration has been successful reducing considerably solid tumors with no notable side effects unfortunately some tumors are not accessible (brain) and require a systemic administration of the oncolytic viruses. In order to overcome these hurdles, various strategies to enhance the efficacy of oncolytic viruses have been developed which include the insertion of transgenes or combination with immune-modulatory substances.

• Tuberculosis and Respiratory Diseases
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• v.84 no.2
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• pp.96-104
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• 2021

Background: Many chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 ㎍ to indacaterol/glycopyrronium (IND/GLY) 110/50 ㎍ once daily in COPD patients in Korea. Methods: This was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 ㎍ once daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted post-bronchodilator forced expiratory volume in 1 second (FEV₁) ≥50%, post-bronchodilator FEV₁/forced vital capacity <0.7 and smoking history of ≥10 pack-years were included. Eligible patients were randomized in a 1:1 ratio to either IND/GLY or TIO. The primary objective was to demonstrate superiority of IND/GLY over TIO in pre-dose trough FEV₁ at week 12. Secondary endpoints included transition dyspnea index (TDI) focal score, COPD assessment test (CAT) total score, and rescue medication use following the 12-week treatment, and safety assessment. Results: Of the 442 patients screened, 379 were randomized and 347 completed the study. IND/GLY demonstrated superiority in pre-dose trough FEV₁ versus TIO at week 12 (least squares mean treatment difference [Δ], 50 mL; p=0.013). Also, numerical improvements were observed with IND/GLY in the TDI focal score (Δ, 0.31), CAT total score (Δ, -0.81), and rescue medication use (Δ, -0.09 puffs/day). Both treatments were well tolerated by patients. Conclusion: A direct switch from TIO to IND/GLY provided improvements in lung function and other patient-reported outcomes with an acceptable safety profile in patients with mild-to-moderate airflow limitation.