• The Journal of Internal Korean Medicine
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• v.38 no.1
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• pp.72-80
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• 2017

Objective: The purpose of this study is to report the case of a patient with recurring non-small cell lung carcinoma (NSCLC) taking Samchilchoongcho-Jung with Afatinib. Methods: An NSCLC patient diagnosed with multiple bone and pulmonary metastasis was taking Afatinib (20 mg/day) and suffering from stomatitis caused by the Afatinib. The patient was treated with Samchilchoongcho-Jung (1,500 mg/ day) for 3 months. The tumor size was measured with computed tomography, and laboratory findings, including tumor markers (CEA, Cyfra 21-1), were also followed up. Stomatitis was measured by a numeric rating scale, and adverse events were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0. Results: After combined treatment, stable disease was shown on computed tomography. The tumor marker levels of CEA and Cyfra 21-1 were decreased, and the stomatitis significantly improved. NCI-CTCAE 4.0 showed no adverse events. Conclusion: This case study suggests that Samchilchoongcho-Jung may have a synergic effect, in conjunction with Afatinib, on the treatment of patients with recurring NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.67 no.2
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• pp.121-126
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• 2009

Background: Pemetrexed has been prescribed newly as a second line chemotherapy in advanced non-small cell lung carcinoma (NSCLC). The aim of study was to determine the efficacy and toxicity of pemetrexed in advanced NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC were evaluated from June 2006 to December 2008. The patients had relapsed or progressed after prior chemotherapy treatment. They were treated with intravenous pemetrexed $500mg/m^2$ for 10 min on Day 1 of each 21-day cycle. Results: A total of 89 patients were eligible for analysis. The response rate and disease control rate were 11% and 66%. Non-squamous cell carcinoma histology was significantly associated with a superior response rate (p=0.035) and disease control rate (p=0.009) than squamous cell carcinoma histology. The median survival time was 13 months and the median progression free survival time was 2.3 months. The median survival time of patients with ECOG PS 0~1 was 13.2 months, whereas median survival time was 11.6 months for patients with PS 2 (p=0.002). The median progression free survival time of patients with PS 0~1 were 3.8 months, but 2.1 months for patients with PS 2 (p=0.016). The median progression free survival time of smokers with non-squamous cell carcinoma was 3.4 months, which was significant (p=0.014). Grade 3~4 neutropenia were seen in 7.9% patients. Conclusion: Pemetrexed has efficacy in patients who had prior chemotherapy with advanced NSCLC and less hematologic toxicity.

• Journal of Korean Traditional Oncology
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• v.24 no.1
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• pp.1-9
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• 2019

Objective: The purpose of this study is to report the clinical effectiveness of advanced non-small cell lung cancer (NSCLC) with Samchilchoongcho-Jung (HAD-B1) in conjunction with Alectinib. Methods: The patient was diagnosed with Anaplastic lymphoma kinase (ALK) mutated (2+) non-small cell lung cancer adenocarcinoma stage IV, suffering from edema of lower extremities, dyspnea, pleural effusion, general weakness, insomnia. The patient being treated with Alectinib was treated with Samchilchoongcho-Jung (HAD-B1) for disease control and symptom management. The clinical outcomes were measured by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), Numeral rating scale (NRS) and Eastern Cooperative Oncology Group (ECOG). Results: After treatment, dyspnea and edema of lower extremities was relieved from NRS 7 to 5, and 6 to 1 respectively. And ECOG score of the patient was improved from grade 3 to 2. During and after treatment, we didn't find any severe toxicities on laboratory findings. Conclusion: This case study suggests that Samchilchoongcho-Jung (HAD-B1) may improve symptom relief and life quality of NSCLC patient in conjunction with Alectinib.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.382-392
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• 2003

Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.339-353
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• 1994

Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.311-319
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• 1993

The retrospective analysis was performed on 37 patients with stage III non small cell lung cancer who received the radiotherapy from Feb. 1986 to Dec. 1990 at the Dept. of Radiation Oncology, National Medical Center. This analysis, with 29 patients $(78.4\%)$ having been followed from 10 to 60 months, was done to know the survival rate and significant prognostic factor. The actuarial 2,5-year survival rates were $20.6\%,6.9\%$ in our all patients and median survival time was 10 months. Of patients with KPS (Karnofsky prformance status) greater than $80\%,$ the 2, 5 year survival rate and median survival time were $29.2\%,9.7\%$ and 13 months, respectively. The 2-year survival rate and median survival time of patients with KPS less than $80\%\;were\;13.7\%$ and 7 months, respectively. The survival difference according to performance status was statisticaly significant $(29.2\%\;vs.\;13.7\%)(p<0.05).$ In stage IIIa, the 2,5-year survival rate and median survival rate and median survival time were $29.2\%,9.7\%$ and 12 months, respectively. The 2-year survival rate and metian survival time of stage IIIb were $8.6\%$ and 10 months, respectively. The survival difference between stage IIIa and IIIb did not show statistical significance (p>0.1). Of the prognostic factors, the difference of survival rate by initial performance status was statistically significant (p<0.05). But the difference of survival rates by pathologic cell type, stage, total radiation dose, radiotherapy response, and cmbination with chemotherapy were not statistically significant.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.175-184
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• 1994

From March 1983 through January 1990, two hundred sixty six patients with non-small cell lung cancer were treated with external radiation therapy at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. A retrospective analysis was performed on eligible 116 patients who had been treated with radiation dose over 40 Gy and had been able to be followed up. There were 104 men and 12 women. The age ranged from 33 years to 80 years (median ; 53 years). Median follow up period was 18.8 months ranging from 2 months to 78 months. According to AJC staging system, there were 18($15.5\%$) patients in stage II, 79($68.1\%$) patients in stage III and 19($16.4\%$) patients in stage IV. The Pathologic classification showed 72($62.8\%$) squamous cell carcinomas, 16($13.8\%$) adenocarcinomas, 7($6\%$) large cell carcinomas, 5($4\%$) undifferentiated carcinomas, and 16($13.8\%$) un-known histology. In Karnofsky performance status, six ($5.2\%$) patients were in range below 50, 12($10.4\%$) patients between 50 and 60, 46($39.6\%$) patients between 60 and 70, 50($44.0\%$) patients between 70 and 80 and only one ($0.8\%$) patient was in the range over 80. Sixty ($51.7\%$) patients were treated with radiation therapy (RT) alone. Thirty three ($28.4\%$) patients were treated in combination RT and chemotherapy, twenty three ($19.8\%$) patients were treated with surgery followed by postoperative adjuvant RT and of 23 Patients above, five ($4.3\%$) patients, were treated with postoperative RT and chemotherapy. Overall response according to follow-up chest X-ray and chest CT scans was noted in $92.5\%$ at post RT 3 months. We observed that overall survival rates at 1 year were $38.9\%$ in stage II, $27.8\%$ in stage III, and $11.5\%$ in stage IV, and 2 year overall survival rates were $11.1\%$ in stage II, $20.8\%$ in stage III and $10.5\%$ in stage IV, respectively. We evaluated the performance status, radiation dose, age, type of histology, and the combination of chemotherapy and/or surgery to see the influence on the results fellowing radiation therapy as prognostic factors. Of these factors, only performance status and response after radiation therapy showed statistical significance (P<0.05)

• Progress in Medical Physics
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• v.19 no.4
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• pp.263-268
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• 2008

The application of a respiratory gated radiotherpy method to the lung radiation surgery was evaluated compared with the conventional method in which the whole tumor motion range is considered in the delineation of PTV (Planning target volume). The four dimensional CT simulation images were acquired for the five NSCLC (Non-small cell lung cancer) patients for radiation surgery. The respiratory gated plan was prepared with the 50% phase CT images and the conventional method was planned based on the ITV (Internal target volume) which include all the target volumes created in each phase CT images within a whole respiratory period. The DVH (Dose volume histogram) of OAR (Organ at risk) which calculated in each method was compared for the evaluation of the plan properness. The relative decrease of OARs' DVH were verified in the application of respiratory gated method. The average decrease rate were $16.88{\pm}9.97%$ in the bronchus, $34.13{\pm}19.15%$ in the spinal cord, $28.42{\pm}18.49%$ in the chest wall and $32.48{\pm}16.66%$ in the lung. Based on these results, we can verified the applicability and the effectiveness of the respiratory gated method in the lung radiation surgery.

• Tuberculosis and Respiratory Diseases
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• v.53 no.4
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• pp.369-378
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• 2002

Background : The effects of chemotherapy on pulmonary function are mainly a reduced diffusion capacity and a restrictive ventilatory impairment. Exercise can expose cardiovascular and pulmonary abnormalities not evident at rest. Exercise related cardiopulmonary function is important in patients with malignant disease as a determinant of quality of life. We performed this study to evaluate the changes of body composition and cadiopulmonary exercise perfoemance of patients with locally advanced, non-small cell, lung cancer (NSCLC) before and after chemotherapy. Methods : We evaluated resting pulmonary function, body composition, physiologic performance status, and cardiopulmonary exercise function in 11 patients with locally advanced NSCLC, at diagnosis and prior to the fourth cycle of chemotherapy. Results : After chemotherapy, 4 patients (36.4%) showed partial response and 7 (63.4%) had stable disease. After chemotherapy, diffusion capacity of the lung for carbon monoxide was reduced ($89.7{\pm}34.1%$, vs. $71.9{\pm}20.5%$) but not significantly. There were no significant changes in body composition or the state of physiologic performance after chemotherapy. There was a significant impairment of cardiopulmonary exercise tolerance in patients with NSCLC, evidenced by a reduction of maximal oxygen uptake ($VO_2$max, ml/kg/min, $17.9{\pm}2.6$ : $12.6{\pm}6.1$, <0.05) and $O_2$pulse ($O_2$ pulse, ml/beat, $7.0{\pm}1.7$, $5.2{\pm}2.1$, <0.05). Conclusion : Systemic chemotherapy resulted in a loss of cardiopulmonary exercise function in patients with locally advanced NSCLC within the short-term period, but not a physiologic change of body composition within the same period.