• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.463-467
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• 2012

Purpose: To assess the safety and efficacy of a gemcitabine plus docetaxel regimen as a second line therapy for patients with advanced soft tissue sarcoma (STS) resistant to doxorubicin and ifosfamide-based therapy. Patients and Methods: Medical records of 64 patients with advanced STS who received gemcitabine plus docetaxel regimen as a second line treatment between May 2006 and June 2011 were examined. All patients had been previously treated with doxorubicin plus ifosfamide-based regimen at first line setting. Patients received gemcitabine 900 $mg/m^2$ on days one and eight intravenously over 90 minutes, followed by docetaxel 75 $mg/m^2$ on day eight intravenously over one hour. Cycles were repeated every 3 weeks. Results: The male-to-female ratio was 37/27 and the median age was 44 years (range; 19-67 years). Objective responses were observed in 13 (20.3 %) patients (2 CR, 11 PR) and stable disease in 21 (32.8 %). Total clinical benefit (CR+PR+SD) was observed in 34 (53.1 %). Median overall survival (OS) was 18 months (95% confidence interval (CI):12.1-23.9) and Median time to progression (TTP) was 4.8 months (95% CI: 3.6-6). A total of 243 cycles of chemotherapy were administered. The median number of cycle was 3 (range;1-11). The most common grade 3-4 hematologic toxicity was neutropenia (35.9 %). The most common nonhematologic toxicities consisted of nausea/vomiting (37.5 %), mucositis (32.8 %), peripheral neuropathy (29.7%), and fatigue (26 %). There was no toxicity-related death. Conclusion: The combination of gemcitabine plus docetaxel is an active and tolerable regimen as a second line therapy for patients with advanced soft tissue sarcoma who have failed doxorubicin and ifosfamide-based therapy.

• Molecular & Cellular Toxicology
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• v.1 no.4
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• pp.256-261
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• 2005

The recent DNA microarray technology enables us to understand gene expression profiling in cell line and animal models. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, microarray system has been used for the prediction of toxicity through gene expression induced by toxicants. It has been shown that compounds with similar toxic mechanisms produce similar changes in gene expression in vivo system. Here we focus on the use of toxicogenomics for the determination of gene expression analysis associated with hepatotoxicity in rat liver and cell line (WB-F344). Methotrexate (MTX) is a chemotherapy agent that has been used for many years in the treatment of cancer because it affects cells that are rapidly dividing. Also it has been known the toxicity of MTX, in a MTX abortion, it stops embryonic cells from dividing and multiplying and is a non-surgical method of ending pregnancy in its early stages. We have shown DNA microarray analyses to assess MTX-specific expression profiles in vivo and in vitro. Male Sprague-Dawely VAF+ albino rats of 5-6 weeks old and WB-F344 cell line have been treated with MTX. Total RNA was isolated from Rat liver and cell line that has treated with MTX. 4.8 K cDNA microarray in house has been used for gene expression profiling of MTX treatment. We have found quite distinct gene expression patterns induced by MTX in a cell line and in vivo system.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.230-240
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• 2002

Background : The majority of chemotherapy-treated small cell lung cancers(SCLC) patients eventually recur. Although many patients are in excellent physical condition at the time of recurrence, few drugs or drug combinations are capable of effecting a tumor regression in this setting. Topotecan, a topoisomerase I inhibitor, is one of the more widely studied single afents in SCLC. The aim of this study was to determine the response rate, survival and toxicity of topotecan as a second line traeatment SCLC. Materials and Methods : 19 patients with measurable SCLC, progressive during the first line chemotherapy (9 cases) or recurrent after the first line chemotherpy(10 cases), were enrolled in this study. Topotecan was administered as a 30-minute daily infusion at a dose of 1.5mg/$m^2$ for 5 consecutive days, every 3 weeks. Results : The overall response rate was 26.3%(5/19, CR 2, PR 3, SD 3, PD 11). The median survival was 24 weeks. The response rate and survival were poor in the nonresponders during first chemotherapy, those who were refractory to the first chemotherapy(recurrent within 3 months after completion of first chemotherapy) and extensive disease, but the results were not statistically significant. The toxicities were mainly hematologic and anemia grade III 1/90, leukopenia grade III 6/90 IV 4/90, thrombocytopenia grade III 1/90 IV 1/90, vomiting grade III 1/90 of cycles were occurred. There was no treatment-related deaths due to severe myelosuppression. Conclusion : Topotecan can be an active second line chemotherapeutic agent for treating SCLC.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.98-106
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• 2003

Background : To evaluate the efficacy and safety of gemcitabine and cisplatin chemotherapy in advanced non-small cell lung cancer (NSCLC). Materials and Methods : Forty patients (21 men, 19 women ; age range, 37 to 73 years; median, 63 years) with unresectable stage IIIB to IV NSCLC were evaluated. Patients received cisplatin $60mg/m^2$ (Day 1), gemcitabine $1200mg/m^2$ (Day 1 and 8) every 21 days. Eighteen patients had stage IIIB disease and 22 had stage IV. There were 28 patients of adenocarcinoma (70.0%), 11 of squamous cell carcinoma (27.5%), and one of large cell carcinoma (2.5%). Results : Of 40 patients, no patients showed complete response while 15(37.5%) showed partial response, 7(17.5%) had stable diseases, 18(45%) had progressive diseases. During a total of 195 courses of chemotherapy, grade 3 or more granulocytopenia and thrombocytopenia occured in 12.5% and 2.5% of patients respectively. Non-hematologic toxicity was mild and easily controlled. There was one case of treatment-related death by pneumomia. The median survival was 55 weeks (95% CI, 34~75weeks), and the time to progression was 19 weeks (95% CI, 16~23weeks). One year survival rate was 55% and 2 year survival rate was 10%. Conclusion : The efficacy of cisplatin and gemcitabine combination chemotherapy was acceptable in the treatment of advanced NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.309-316
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• 2002

Background: To evaluate the efficacy and toxicity of combination chemotherapy using ifosfamide, cisplatin, and etoposide in patients with advanced non-small cell lung cancer(NSCLC). Materials and methods: Thirty-three patients with inoperable NSCLC(stage IIIb+IV) who had measurable diseases, and had not been treated with chemotherapeutic drugs, were enrolled in this study(from March 1995 to December 1996). The patients received ifosfamide($1500mg/m^2/day$, a full drop with Mesna on days 1-5), Cisplatin ($80mg/m^2/day$ infusion with a hydration on day 2), and Etoposide ($100mg/m^2/day$ infusion for 2 hours on days 1-3). The treatment was repeated every 4 weeks. Results: Ten patients showed a partial responses (30.3%). The overall survival time of the responders was longer than that of the non-responders (median 55 vs 22 weeks, p=0.01). The toxicities of this treatment were tolerable. Grade 3 or 4 leukopenia was observed in 21%. There was 1 death related to febrile neutropenia. The non-hematologic toxicity was mild. The relative dose intensity given to the patients was 0.86 ifosfamide, 0.87 cisplatin, and 0.89 etoposide, showing an average dose intensity of 0.87. Conclusions: A combination regimen of ifosfamide, cisplatin, and etoposide is effective and tolerable for treating advanced non-small cell lung cancer.

• 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.

• Journal of Gynecologic Oncology
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• v.29 no.6
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• pp.97.1-97.12
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• 2018

Objective: Women with cervical cancer (CC) found to have positive surgical margins, positive lymph nodes, and/or parametrial invasion receive a survival benefit from postoperative chemoradiotherapy (CRT) vs. radiation therapy (RT) alone. However, older women may not benefit to the same extent, as they are at increased risk of death from non-oncologic causes as well as toxicities from oncologic treatments. This study sought to evaluate whether there was a survival benefit of CRT over RT in elderly patients with cervical cancer. Methods: The National Cancer Database was queried for patients ${\geq}70$ years old with newly diagnosed IA2, IB, or IIA CC and positive margins, parametrial invasion, and/or positive nodes on surgical resection. Statistics included logistic regression, Kaplan-Meier overall survival (OS), and Cox proportional hazards modeling analyses. Results: Altogether, 166 patients met inclusion criteria; 62 (37%) underwent postoperative RT and 104 (63%) underwent postoperative CRT. Younger patients and those living in areas of higher income were less likely to receive CRT, while parametrial invasion and nodal involvement were associated with an increased likelihood (p<0.05 for all). There were no OS differences by treatment type. Subgroup analysis by number of risk factors, as well as each of the 3 risk factors separately, also did not reveal any OS differences between cohorts. Conclusion: In the largest such study to date, older women with postoperative risk factor(s) receiving RT alone experienced similar survival as those undergoing CRT. Although causation is not implied, careful patient selection is paramount to balance treatment-related toxicity risks with theoretical outcome benefits.

• Radiation Oncology Journal
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• v.36 no.1
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• pp.17-24
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• 2018

Purpose: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. Materials and Methods: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. Results: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. Conclusion: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.415-428
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• 2003

Background : This study assessed the efficacy and toxicity of etoposide and carboplatin(EC) combination regimen as a first line therapy for small cell lung cancer(SCLC), and determined the efficacy and toxicity of topotecan for relapsed SCLC. Methods : One hundred and ten patients with previously untreated SCLC received etoposide($100mg/m^2$ i.v., day 1 to 3) and carboplatin($300mg/m^2$ i.v., day 1) combination chemotherapy every 3 weeks. For patients with relapsed SCLC after EC therapy, topotecan($1.5mg/m^2$) was administered for 5 consecutive days every 3 weeks. Response rate, survival and toxicity profiles were assessed. Response was recorded as CR(complete remission), PR(partial remission), SD(stable disease) and PD(progressive disease). Results : One hundred and one patients were assessed for response to EC. Overall response rate to EC was 57.4%(CR 15.8%, PR 41.6%) with a time to progression of 10.3 months(median). The toxicity was tolerable and there was no treatment-related death. Twenty one relapsed SCLC patients were treated with topotecan. Of those who relapsed within 3 months of EC(refractory relapse, RR), 15.4%(2/13) showed PR, while of those who relapsed after 3 months(sensitive relapse, SR), 25%(2/8) exhibited PR. Grade 4 neutropenia was noted in 9.5% and 14.3% showed thrombocytopenia(G4). Conclusion : The EC regimen showed a moderate response rate for SCLC with minimal toxicity. The use of topotecan for relapsed SCLC warrants further investigation.

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.154-164
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• 2007

Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. Methods: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan $60mg/m^2$ was administered intravenously on days 1 and 8 in combination with cisplatin $60mg/m^2$ on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. Results: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin $19.6mg/m^2$/week and irinotecan $38.2mg/m^2$/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. Conclusion: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.