• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1863-1867
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• 2012

Background: Maintenance chemotherapy is one strategy pursued in recent years with intent to break through the chemotherapy plateau for advanced non-small cell lung cancer (NSCLC). However, given the toxicity, platinum-based combinations are rarely given for this purpose. We carried out the present prospective study of triplet platinum-based combination sequential chemotherapy in advanced NSCLC to investigate if patients could tolerate and benefit from such intensive treatment. Methods: From Dec 2003 to Dec 2007, 190 stage IIIB and IV NSCLC patients in Sun yat-sen University sequentially received the 3 platinum-based combination (TP-NP-GP) treatment (T: paclitaxol175$mg/m^2$ d1; N: vinorelbine25$mg/m^2$ d1 and 8; G: gemcitabine1$g/m^2$ d1 and 8; P: cisplatin20$mg/m^2$ d1-5; repeated every 3 weeks). Patients were followed up to at least 3 years to obtain survival data. Treatment toxicities and the quality of life (QOL) were assessed during the whole treatment. Results: There were 187 patients evaluable. The TP, NP and GP response rates with sequential use were 42.8% (80/187), 41.1% (65/158) and 28.8% (21/73) respectively. Median survival time was 18.2 months and the 1, 2 and 3 year overall survival (OS) rates were 78.7%, 38.5% and 21.3%. Patients receiving > 6 cycles of chemotherapy had significantly longer OS and TTP (MST 25.3 vs. 14.5 months, TTP 15.1 vs. 9.1 months). The QOL on the whole for the patients was improved after chemotherapy. Conclusions: The sequential chemotherapy strategy with triplet platinum-based combination regimens can improve the survival outcome and the quality of life of advanced non-small cell lung cancer patients.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.230-236
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• 2006

$\underline{Purpose}$: To analyze the response, toxicity, patterns of failure and survival rate of patients with locally advanced non-small cell lung cancer who were treated with concurrent chemoradiotherapy with weekly paclitaxel. $\underline{Materials\;and\;Methods}$: Twenty-three patients with locally advanced non-small cell lung cancer patients who received radical chemoradiotherapy from October 1999 to September 2004 were included in this retrospective study. Patients received total $55.4{\sim}64.8$ (median 64.8) Gy (daily 1.8 Gy per fraction, 5 days per weeks) over $7{\sim}8$ weeks. 50 or $60\;mg/m^2$ of paclitaxel was administered on day 1, 8, 15, 22, 29 and 36 of radiotherapy. Four weeks after the concurrent chemoradiotherapy, three cycles of consolidation chemotherapy consisted of paclitaxel $135\;mg/m^2$ and cisplatin $75\;mg/m^2$ was administered every 3 weeks. $\underline{Results}$: Of the 23 patients, 3 patients refused to receive the treatment during the concurrent chemoradiotherapy. One patient died of bacterial pneumonia during the concurrent chemoradiotherapy. Grade 2 radiation esophagitis was observed in 4 patients (17%). Sixteen patients received consolidation chemotherapy. During the consolidation chemotherapy, 8 patients (50%) experienced grade 3 or 4 neutropenia and one of those patients died of neutropenic sepsis. Overall response rate for 20 evaluable patients was 90% including 4 complete responses (20%) and 14 partial responses (70%). Among 18 responders, 9 had local failure, 3 had local and distant failure and 2 had distant failure only. Median progression-free survival time was 9.5 months and 2-year progression-free survival rate was 19%. Eleven patients received second-line or third-line chemotherapy after the treatment failure. The median overall survival time was 21 months. 2-year and 5-year survival rate were 43% and 33%, respectively. Age, performance status, tumor size were significant prognostic factors for progression-free survival. $\underline{Conclusion}$: Concurrent chemoradiotherapy with weekly paclitaxel revealed high response rate and low toxicity rate. But local failure occurred frequently after the remission and large tumor size was a poor prognostic factor. Further investigations are needed to improve the local control.

• Journal of Chest Surgery
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• v.33 no.8
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• pp.662-668
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• 2000

Background: Many recent results of clinical trials show that pre-operative concurrent chemoradiotherapy and surgical resection could increase the survival of N2 positive stage IIIA non-small cell lung cancer. This study was performed to assess the feasibility, toxicity, and affect rates of concurrent chemoradiotherapy and surgical resection in N2 positive stage IIIA non-small cell lung cancer. Material and Method: Thirty-one patients who underwent preoperative concurrent chemoradiotherapy for N2 positive stage IIIA non-small-cell lung cancer from May 1997 to April 1999 were entered into the study. Mean age was 61 yrs(43∼70 yrs), There were 24 men and 7 women. The confirmation of N2 disease were achieved through mediastinoscopic biopsy(24) and CT scans(7). Induction was achieved by two cycles of cisplatin and etoposide(EP) plus concurrent chest radiotherapy to 45 Gy. Resections were done at 3 weeks after the complection of preoperative concurrent chemoradiotherapy. Resections were performed in 23 patients, excluding 5 refusals and 3 distant metastasis. Result: All patients were compled the thoracic radiotherapy except one who had distant metastasis. Twenty three patients were completed the planned 2 cycles of EP chemotherapy, and 8 patients were received only 1 cycle for severe side effects(6), refusal(1), and distant metastasis(1). There was one postoperative mortality, and the cause of death was ARDS. Three patients who had neutropenic fever and one patient who had radiation pneumonitis were required admission and treatment. Esophagitis was the most common acute side effect, but relatively well-tolerated in most patients. The complection rate of concurrent chemoradiotherapy was 74%, resection rate was 71%, pathologic complete remission rate was 13.6%, and pathologic down-staging rate was 68%. Conclusion: Morbidity related to each treatment was acceptable and many of the patients have benefited down staging of its disease. Further prospective, preferably randomized, clinical trials of larger scale may be warranted to confirm the actual benefit of preoperative concurrent chemoradiotherapy and surgical resection in N2-positive stage IIIA non-small cell lung cancer.

• Radiation Oncology Journal
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• v.15 no.1
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• pp.27-36
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• 1997

Purpose : This study was tried to evaluate the Potential benefits of concurrent chemoradiation therapy (low dose daily cisplatin combined with split course radiation therapy) compared with conventional radiation therapy alone in stage III non-small cell lung cancer. The end points of analyses were response rate. overall survival, survival without locoregional failure, survival without distant metastasis, prognostic factors affecting survival and treatment related toxicities. Materials and Methods : Between April 1992 and March 1994, 32 patients who had stage III non-small cell lung cancer were treated with concurrent chemoradiation therapy. Radiation therapy for 2 weeks (300 cGy given 10 times up to 3000 cGy) followed by a 3 weeks rest period and then radiation therapy for 2 more weeks (250 cGy given 10 times up to 2500 cGy) was combined with $6mg/m^2$ of cisplatin. Follow-up period ranged from 13 months to 48 months with median of 24 months. Historical control group consisted of 32 patients who had stage III non-small cell lung cancer were received conventionally fractionated (daily 170-200 cGy) radiation therapy alone. Total radiation dose ranged from 5580 cGy to 7000 cGy with median of 5940 cGy. Follow-up Period ranged from 36 months to 105 months with median of 62 months. Result : Complete reponse rate was higher in chemoradiation therapy (CRT) group than radiation therapy (RT) group (18.8% vs. 6.3%, CRT group showed lower in-field failure rate compared with RT group(25% vs. 47%. The overall survival rate had no significant differences in between CRT group and RT group (17.5% vs. 9.4% at 2 years). The survival without locoregional failure (16.5% vs. 5.3% at 2 years) and survival without distant metastasis (17% vs. 4.6% at 2 years) also had no significant differences. In subgroup analyses for Patients with good performance status (Karnofsky performance scale 80), CRT group showed significantly higher overall survival rate compared with RT group (62.5% vs. 15.6% at 2 years). The prognostic factors affecting survival rate were performance status and pathologic subtype (squamous cell cancer vs. nonsquamous cell cancer) in CRT group. In RT alone group, performance status and stage (IIIa vs IIIb) were identified as a Prognostic factors. RTOG/EORTC grade 2-3 nausea and vomiting(22% vs 6% and bone marrow toxicities (25% vs. 15.6% were significantly higher in CRT group compared with RT alone group. The incidence of RTOG/EORTC grade 3-4 pulmonary toxicity had no significant differences in between CRT group and RT group (16% vs. 6%. The incidence of WHO grade 3-4 pulmonary fibrosis also had no significant differences in both group (38% vs. 25%. In analyses for relationship of field size and Pulmonary toxicity, the Patients who treated with field size beyond 200cm2 had significantly higher rates of pulmonary toxicities. Conclusion : The CRT group showed significantly higher local control rate than RT group. There were no significant differences of survival rate in between two groups. The subgroup of patients who had good performance status showed higher overall survival rate in CRT group than RT group. In spite of higher incidence of acute toxicities with concurrent chemoradiation therapy, the survival gain in subgroup of patients with good performance status were encouraging. CRT group showed higher rate of early death within 1 year, higher 2 year survival rate compared with RT group Therefore, to evaluate the accurate effect on survival of concurrent chemoradiation therapy, systematic follow-up for long term survivors are needed.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.78-88
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• 2002

Experimental animals were divided into 5 groups; normal, cadmium control, and 3 experimental groups. Cadmium control and experimental groups were exposed to 1 mg/㎥ of cadmium aerosol in air by inhalation exposure for 6 hours/day, 5 days/week during 4 weeks. Dosages of 20, 40, and 80mg/kg of extracts of persimmon leaves were intraperitoneally injected to experimental groups respectively and several toxicological parameters and induction of metallothionein were measured from the rats that inhaled cadmium aerosol in air. The results of this study were as follows. Cadmium concentration that cadmium control and experimental groups were inhaled was 0.980±0.061 mg/㎥. Mass median diameter of cadmium aerosol for inhalation exposure was 4.93±0.483㎛. Cadmium content of normal group in lung was 0.088㎍/g and the highest cadmium content in lung, 55.492㎍/g was from 80mg/kg dose group. Cadmium concentration of normal group in blood was 0.348㎍/100㎖ and the highest cadmium concentration in blood, 2.642㎍/100㎖ was from cadmium control. Cadmium concentration of normal group in liver was 0.010㎍/g and the highest cadmium concentration in liver, 31.100㎍/g was from 20mg/kg dose group. Cadmium concentration of normal group in kidney was 0.030㎍/g and the highest cadmium concentration in kidney, 2.526㎍/g was from cadmium control. Cadmium concentration of normal group in intestine was O.064㎍/g and the highest cadmium concentration in intestine, 0.300㎍/g was from 80mg/kg dose group. The highest cadmium concentration in urine by week was 6.080㎍/day from 20mg/kg dose group in the fouth week and the highest cadmium concentration in feces by week was 341.731㎍/day from 20mg/kg dose group in the fouth week. Metallothionein concentration of normal group in lung was 5.769㎍/g and the highest in lung, 30.986㎍/g was from 80mg/kg dose group. Metallothionein concentration of normal group in liver was 38.856㎍/g and the highest in liver, 169.378㎍/g was from 40mg/kg dose group. Metallothionein concentration of normal group in kidney was 22.228㎍/g and the highest in kidney, 47.898㎍/g was from 80mg/kg dose group. Metallothionein concentration of normal group in intestine was 2.170㎍/g and the highest in intestine, 13.642㎍/g was from 80mg dose group.

• Journal of Food Hygiene and Safety
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• v.13 no.2
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• pp.87-93
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• 1998

The tannic acid (0.5 mg/ml, 1.0 mg/mi, 2.0 mg/ml) and/or cadmium (20 mg/kg) were administered by oral administration. The results were as follows: 1. There were adverse effects on the weight changes and water consumption. But, the extent of adverse changes were decreased by tannic acid administration. 2. Also, there were some significant changes in organ weight, especially relative liver weight and relative brain weight by cadmium administration, but Ta1.0 group was significant changes in relative liver weight, relative lung weight and relative thymus weight compared with control group. 3. In the hematological patterns of administered mice, there were significant changes between cadmium treated groups and control group. Hemoglobin contents, packed cell volume, platelet count and neutrophill count were significantly change compared with control group. These changes were not shown in tannic acid treated group. 4. There were serological enzymatic changes in the cadmium treated mouse. In the tannic acid treated group 0.5, 1.0, 2.0 mg/ml, ALT, AST, BUN and creatinine were recovered to the extent of control group. From the above results, the tannic acid has some possible alleviative effects of cadmium toxicity upto the 2.0 mg/ml/day of oral dose for 4 weeks. But we need further study of mechanism for toxicty alleviating action of tannic acid to the heavy metals like cadmium.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.293-299
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• 2000

Purpose :We conducted a prospective non-randomized clinical study to evaluate the efficacy and toxic of the preoperative concurrent chemoradiotherapy for locally advanced unresectable rectal cancer. Materials and Methods: Between January 1995 and June 1998, 37 conecutive patients with locally unresectable advanced rectal cancer were entered into the study. With 3- or 4- fields technique, a total of 45 Gy radiation was delivered on whole pelvis, followed by 5.4 Gy boost to the primary tumor in some cases. Chemotherapy was done at the first and fifth week of radiation with bolus i.v. 5-Fluorouracil (FU) 370$\~$450 mg/m$^{2}$, days 1$\~$5, plus Leucovorin 20 mg/m$^{2}$, days 1$\~$5. OF 37 patients, 6 patients did not receive all planned treatment course (refusal in 4, disease progression in 1, metastasis to lung in 1). Surgical resection was undergone 4$\~$6 weeks after preoperative concurrent chemoradiotherapy. Results :Complete resection rate with negative margins was 94$\%$ (29/31). Complete response was seen in 7 patients (23$\%$) clinically and 2 patients (6$\%$) pathologically. Down staging of tumor occured in 21 patients (68$\%$). Treatment related toxicity was minimal except grade III & IV leukopenia in 2 patients, respectively. Conclusion : Preoperative concurrent chemoradiotherapy in locally advanced rectal cancer was effective in inducing down staging and complete resection rate. Treatment related toxicity was minimal. Further follow up is on-going to determine long term survival following this treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7367-7369
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• 2013

Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-${\beta}$) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.740-747
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• 2000

Background : To compare the efficacies and side effects of etoposide, cisplatin/cyclophosphamide, adriamycin, vincristine(VPP/CAV) with those of carboplatin etoposide(CE) in extensive stage small cell lung cancer patients. Method : Patients with extensive stage small lung cancer who has measurable disease were eligible. VPP/CAV group(n=22) was treated with cisplatin(60mg/$m^2$ iv. D1) etoposide(100mg/$m^2$ iv. D1-3), and 3 weeks later cyclophosphamide(1000mg/$m^2$ iv. D1), adriamycin( 40mg/$m^2$ iv. D1), and vincristine(1.4mg/$m^2$ iv. D1), were administered alternatively. CE group(n=22) was treated with carboplatin(325mg/$m^2$ iv. D1) and etoposide (100mg/$m^2$ iv. D1-3) ; repeated treatment was performed every 3 weeks. Result : Forty four patients were eligible for the study. The overall response rate was 61.4% (complete remission rate 0%, partial response rate 61.4%, stable disease rate 25%, progressive disease rate 13.6%), and median survival was 10.8 months. In VPP/CAV group, response rate was 54.5% (complete remission rate 0%, partial response rate 54.4%, stable disease rate 27.3%, progressive disease rate 18.2%), and, in carboplatin/etoposide group, the response rate was 68.2%(complete remission rate 0%, partial response rate 68.2%, stable disease rate 22.7%, progressive disease rate 9.1%). The median survival time was 9.5 months in the VPP/CAV group and 11 months in CE group. The toxicity of both group was moderate, and anemia was more frequent in the CE group. Conclusion : VPP/CAV regimen and CE regimen produced similar response rates and survival times in extensive stage small cell lung cancer patients. CE regimen may be effective as part of the initial therapy for extensive stage small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.257-264
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• 2004

Background : There are many combinations of treatment for locally advanced non-small cell lung cancer (NSCLC). Recent studies have showed the efficacy of concurrent chemoradiotherapy (CCRT) in NSCLC. At present, however, there is no consensus about the optimal dosages and timing of radiation and chemotherapeutic agents. The aims of study were to determine the feasibility, toxicity, response rate, and survival rate in locally advanced NSCLC patients treated with doxetaxel and cisplatin based CCRT. Method : Sixteen patients with unresectable stage III NSCLC were evaluated from May 2000 until September 2001. Induction chemoradiotherapy consisted of 3 cycles of docetaxel (75 $mg/m^2/IV$ on day 1) and cisplatin (60 $mg/m^2/IV$ on day 1) chemotherapy every 3 weeks and concomitant hyperfractionated chest irradiation (1.15 Gy/BID, total dose of 69 Gy) in 6 weeks. Patient who had complete or partial response, and stable disease were applied consolidation chemotherapy of docetaxel and cisplatin. Results : All patients showed response to CCRT. Four patients achieved complete response (25%), partial responses in 12 patients (75%). The major common toxicities were grade III or more of neutropenia (87.3%), grade III esophagitis (68.8%), pneumonia (18.8%) and grade III radiation pneumonitis (12.5%). Thirteen patients were ceased during follow-up period. Median survival time was 19.9 months (95% CI; 4.3-39.7 months). The survival rates in one, two, and three years are 68.7%, 43.7%, and 29.1%, respectively. Local recurrence was found in 11 patients (66.8%), bone metastasis in 2, and brain metastasis in 1 patient. Conclusion : The response rate and survival time of CCRT with docetaxel/cisplatin in locally advanced NSCLC were encouraging, but treatment related toxicities were high. Further modification of therapy seems to be warranted.