• Korean Journal of Clinical Pharmacy
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• v.29 no.2
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• pp.101-108
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• 2019

Background: High doses of methotrexate (MTX) are often used in various chemotherapy protocols to treat acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) in children, but its delayed elimination increases the occurrence of adverse events, such as bone marrow suppression. The aim of this study was to investigate the elimination of MTX at 24 and 48 hours. Methods: We retrospectively analyzed electronic medical records of ALL or NHL pediatric patients who received $5g/m^2$ MTX infusion over 24 hours (between June, 2012 and July, 2018) at the Yonsei University Health System, Korea. The delayed elimination of MTX concentrations was assessed with 100 or $150{\mu}M$ MTX at 24 hours, and 2 or $5{\mu}M$ at 48 hours. Results: Among the 85 MTX cycles administered, 23 cycles were classified in delayed elimination group, and 62 cycles showed normal elimination. At 24 hours, the delayed elimination group with MTX concentration > $100{\mu}M$ showed higher percentage than group with MTX concentration < $100{\mu}M$ (45.8% vs. 19.7%, p = 0.015). However, no differences were observed at $150{\mu}M$ MTX (p = 0.66). At 48 hours, the delayed elimination was higher than the normal elimination at both concentration baselines (p < 0.001 at $2{\mu}M$, p = 0.024 at $5{\mu}M$). Conclusions: MTX concentrations greater than $100{\mu}M$ show high probability of delayed elimination at 24 hours. When MTX levels are above normal, leucovorin and hydration regimens should be continued to prevent delayed elimination.

• Journal of Gastric Cancer
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• v.23 no.2
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• pp.315-327
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• 2023

Purpose: Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. Materials and Methods: Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. Results: Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250-0.890; P=0.020). Conclusions: After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

• Tuberculosis and Respiratory Diseases
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• v.62 no.5
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• pp.432-436
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• 2007

Malignant pleural mesothelioma (MPM) is a rare tumor that is difficult to clearly distinguish from an adenocarcinoma but usually has a poor prognosis. Numerous cytotoxic agents have been used in the primary treatment of MPM with limited success. A complete response is unusual and a partial response occurs in less than one-third of patients. Recently, a phase III trial showed that a combination of pemetrexed with cisplatin resulted in a significantly higher response rate and median survival time than with cisplatin alone. We encountered a case of a dramatic tumor response to pemetrexed/cisplatin combination chemotherapy in patients with MPM, which was resistant to the 1st-line gemcitabine/cisplatin therapy. After six cycles of pemetrexed/cisplatin combination chemotherapy, the tumor volume had decreased dramatically with complete symptom relief. There was no chemotherapy-related toxicity or scheduled violation. The patient is under maintenance chemotherapy with the same regimen.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6257-6261
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• 2012

Objective: To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE), combined with portal vein embolization (PVE), and high intensity focused ultrasound (HIFU) sequential therapy in treating patients with hepatocellular carcinoma (HCC). Methods: Patients with inoperative HCC were treated by two methods: in the study group with TACE first, then PVE a week later, and then TACE+PVE every two months as a cycle, after 2~3 cycles finally HIFU was given; in the control group only TACE+PVE was given. Response (CR+PR), and disease control rate (CR+PR+SD), side effects, overall survival and time to progress were calculated. Results: Main side effects of both groups were nausea and vomiting. No treatment related death occurred. In the study group, 32 patients received TACE for overall 67 times, PVE 64 times, and HIFU 99 times; on average 2.1, 2 and 3.1 times for each patient, respectively. In the control group, 36 patients were given TACE 78 times and PVE 74 times, averaging 2.2 and 2.1 times per patient. Effective rate: 25.0% in study group and 8.3% in control group (p>0.05). Disease control rates were 71.9% and 44.4%, respectively (p<0.05). In patients with portal vein tumor thrombus, the rate reduced over 1/2 after treatment was 69.2%(9/13) in the study and 21.4%(3/14) in the control group (p<0.05). Rate of AFP reversion or decrease over 1/2 was 66.7%(16/24) in study and 37%(10/27) (p<0.05) in control group. Median survival time: 16 months in study and 10 months in control group. PFS was 7months in study and 3 months in control group. Log-rank test suggested that statistically significant difference exists between two groups (p=0.024). 1-, 2- and 3-year survival rates were 56.3%, 18.8% and 9.3% in study, while 30.6%, 5.6% and 0 in control group, respectively, with statistically significant difference between two groups (by Log-rank, p = 0.014). Conclusions: The treatment of TACE+PVE+HIFU sequential therapy for HCC increases response rate, prolong survival, and could thus be a safe and effective treatment for advanced cases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.9009-9013
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• 2014

Background: The aim of this study was to explore the efficacy and adverse reactions of CT-guided radioactive 125I-seed implantation treatment combined with chemotherapy for platinum-resistant recurrent ovarian carcinoma. Materials and Methods: From September 2010 to December 2012, 23 patients with platinum-resistant recurrent ovarian carcinoma were enrolled. All the patients refused, could not bear, or were not suitable for surgery. They all had no more than 3 lesions, which were detected and could also be measured by CT. All were clarified as single-lesion or multiple-lesion groups. A total of 41 lesions underwent implantation of from 8 to 106 125I seeds (median=43). Multi-plane implanting was adopted and 125I-seeds of (0.4-0.7)mCi were placed at intervals of (0.5-1.0) cm. After implantation treatment, all patients underwent 4 cycles of chemotherapy with gemcitabine $800mg/m^2$ (days 1, 8 and 15). Results: The outcome was evaluated with CT 3 weeks and every 3 months after implantation treatment. After 6 months, the volume of 32 out of 41 lesions (78.0%) was reduced at least 30%, within which 9 lesions completely disappeared(22.0%). Complete response was observed in 7 cases (30.4%), with a partial response in 4 cases (17.4%), 4 cases stable(17.4%)and 8 cases showing progression (34.8%). The total clinical remission rate was 47.8% (11/23). The clinical remission rate was 77.8% (7/9) in the single-lesion group and 28.6% (4/14) in the multiple-lesion group with a significant difference between the two(P=0.036). The common side effects observed were mild gastrointestinal reactions. Conclusions: 125I-seed implantation combined with chemotherapy applies an effective way in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma with the advantages of high local control rates, good short-term effects, little trauma and less side effects.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5057-5061
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• 2012

Purpose: Chemotherapy-induced anemia (CIA) is one of the most important causes of anemia in cancer patients. This study was conducted to describe the prevalence and characteristics of CIA in solid cancer patients in the Chinese population, and to explore the relationship of white blood cell (WBC) or platelet decrease with CIA. Methods: Data on age, gender, tumor diagnosis, anti-cancer treatment and blood cell analyses were available from 220 untreated non-anemic cancer patients who received at least 2 cycles of chemotherapy, and the data were analyzed to assess their relationship with CIA or its severity. Results: 139 patients (63.2%) presented anemia, most being Grade 1 or 2. Esophageal and lung cancers were associated with a high prevalence. G3/4 leucopenia and decrease of platelets were identified as independent risk factors for the occurrence of CIA. Moreover, G3/4 leucopenia, decrease of platelet and G3/4 thrombocytopenia were found to be also associated with the severity of CIA. Cisplatin-containing regimens were a main potential factor in causing CIA, although significant association was only found on univariate analysis. Conclusion: Anemia or decrease in hematoglobin are common in Chinese cancer patients receiving chemotherapy. Cisplatin-containing regimens might be an important factor influencing the occurrence of CIA. Our analysis firstly described some risk factors, such as decrease of platelets or WBCs, severity of leucopenia or thrombocytopenia, associated with the occurrence and severity of CIA.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.1
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• pp.9-14
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• 2003

Recent studies indicated that cancer cells become resistant to ionizing radiation (IR) and chemotherapy drugs by enhanced DNA repair of the lesions. Therefore, it is expected to increase the killing of cancer cells and reduce drug resistance by inhibiting DNA repair pathways that tumor cells rely on to escape chemotherapy. There are a number of key human DNA repair pathways which depend on multimeric polypeptide activities. For example, Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) on binding to double strand DNA breaks (DSBs) are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and are essential for DNA-dependent protein kinase (DNA-PK) activity. It has been known that DNA-PK is an important factor for DNA repair and also is a sensor-transmitting damage signal to downstream targets, leading to cell cycles arrest. Our ultimate goal is to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. This would greatly facilitate tumor cell cytotoxic activity and programmed cell death through DNA damaging drug treatment. Therefore, we designed a domain of Ku80 mutants that binds to Ku70 but not DNA end binding activity and used the peptide in co-therapy strategy to see whether the targeted inhibition of DNA-PK activity sensitized breast cancer cells to irradiation or chemotherapy drug. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, thus resulting in inactivation of DNA-PK activity. Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to IR or chemotherapy drugs, and the growth of breast cancer cells was inhibited. Additionally, the results obtained in the present study also support the physiological role of resistance of cancer cells to IR or chemotherapy.

• The Journal of Internal Korean Medicine
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• v.42 no.6
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• pp.1341-1348
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• 2021

The purpose of this study is to report the effect of Korean medicine on a squamous cell lung cancer patient with chemotherapy induction peripheral neuropathy (CIPN). A 61-year old male patient, who had received 4 cycles of chemotherapy after lung surgery from squamous cell lung cancer, was treated with acupuncture and herbal medicines, including Uchasingi-hwan and Samchilchoongcho-capsule, to control CIPN and dyspnea on exertion. The degree of pain was assessed by a numeric rating scale (NRS). After receiving acupuncture and herbal medicines, the NRS score for CIPN symptoms was reduced from 4 to 1 and the NRS score for dyspnea on exertion decreased from 3 to less than 1. Korean medicine could therefore be useful in reducing peripheral neuropathy occurring after chemotherapy and dyspnea after lobectomy.

• Radiation Oncology Journal
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• v.18 no.1
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• pp.17-25
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• 2000

Purpose : To evaluate the side effects, pattern of failure, and survival rate according to the sequence of postoperative adjuvant radiotherapy and chemotherapy, patients with stages II and III rectal cancer who had undergone curative resection were randomized to 'early radiotherapy group (arm I)' or' late radiotherapy group (arm II)', then we intend to determine the most effective sequence of the radiotherapy and chemotherapy. Materials and Methods . From January 1996 to March 1999, 313 patients with curatively resected stages II and III rectal cancer have been randomized to' early' or' late' radiation therapy group and received combined chemotherapy (5-FU 375 mg/m$^{2}$/day, ieucovorin 20 mg/m$^{2}$, IV bolus daily Dl-5, 8 cycles) and radiation therapy (whole pelvis with 45 Gy/25 fractions/s weeks). Arm I received radiation therapy from day 1 with first cycle of chemotherapy and arm II received radiation therapy from day 57 with third cycle of chemotherapy after completion of first two cycles. Preliminary analysis was peformed with 228 patients registered up to Jun 1998. Two out of the 228 patients were excluded because of double primary cancer. Median follow-up period was 23 months. Results :Local recurrence occurred in 11 patients (9.7$\%$) for arm I and 9 patients (8$\%$) for arm 11. There was no significant difference between both groups ( p=0.64). However, distant metastasis was found in 22 patients (19.5$\%$) for arm I and 35 patients (31.0$\%$) for arm II and which showed statistically significant difference between the two groups ( p=0.046). And neither 3-year disease-free survival (70.2$\%$ vs 59.2$\%$, p=0.2) nor overall survival (89.4$\%$ vs 88.0$\%$, p=0.47) showed significant differences. The incidence of leukopenia during radiation therapy and chemotherapy was 78.3$\%$ and 79.9$\%$ respectively but leukopenia more than RTOG grade 3 was only 2.1$\%$ and 6.0$\%$ respectively. The incidence of diarrhea more than 10 times per day was significantly higher in the patients for arm I than for arm II (71.2$\%$ vs 41.6$\%$, p=0.02) but this complication was controlled with supportive cares. Conclusion : Regardless of the sequence of postoperative adjuvant radiation therapy and chemotherapy after curative resection for rectal cancer, local recurrence rate was low with combined chemoradlotherapy. But distant metastasis rate was lower in early radiation therapy group than in late radiation therapy group and the reason is unclear. Most patients completed these treatments without severe complication, so these were thought to be safe treatments but the treatment compliance should be improved.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.223-229
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• 2006

$\underline{Purpose}$: Combined modality therapy including chemotherapy, surgery and radiotherapy is considered the standard of care for the treatment of stage III non-small cell lung cancer (NSCLC). This study was conducted to evaluate the efficacy of paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC. $\underline{Materials\;and\;Methods}$: Between July 2000 and October 2005, thirty-nine patients with stage IIIB NSCLC were treated with two cycles of induction chemotherapy followed by concurrent chemoradiotherapy. The induction chemotherapy included the administration of paclitaxel ($175\;mg/m^2$) by intravenous infusion on day 1 and treatment with cisplatin ($75\;mg/m^2$) by intravenous infusion on day 1 every 3 weeks. Concurrent chemoradiotherapy included the use of paclitaxel ($60\;mg/m^2$) plus cisplatin ($25\;mg/m^2$) given intravenously for 6 weeks on day 43, 50, 57, 71, 78 and 85. Thoracic radiotherapy was delivered with 1.8 Gy daily fractions to a total dose of $54{\sim}59.4\;Gy$ in $6{\sim}7$ weeks (median: 59.4 Gy). $\underline{Results}$: The follow up period was $6{\sim}63$ months (median: 21 months). After the induction of chemotherapy, 41.0% (16 patients) showed a partial response and 59.0% (23 patients) had stable disease. After concurrent chemoradiotherapy, 10.3% (4 patients) had a complete response, 41.0% (16 patients) had a partial response, and the overall response rate was 51.3% (20 patients). The 1-, 2-, 3-year overall survival rates were 66.7%, 40.6%, and 27.4% respectively, with a median survival time of 20 months. The 1-, 2-, 3-year progression free survival rates were 43.6%, 24.6%, and 24.6%, respectively, with median progression free survival time of 10.7 months. Induction chemotherapy was well tolerated. Among 39 patients who completed the entire treatment including chemoradiotherapy, 46.3% (18 patients) had esophagitis greater than grade 3 and 28.2% (11 patients) had radiation pneumonitis greater than grade 3. $\underline{Conclusion}$: Paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC seems to be an effective treatment. Occurrence of esophagitis and pneumonitis represents a significant morbidity and suggests a modification of the treatment regimen, either with the chemotherapy schedule or with radiotherapy treatment planning.