• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9823-9829
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• 2014

Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were $43.4{\pm}6.0%$ and $53.2{\pm}6.1%$ respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [$69.8{\pm}10.5%$, $79.8{\pm}9.1%$ for MTX(+) and $31.1{\pm}6.9%$, $42.2{\pm}7.4%$ for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol ($66.7{\pm}13.6%$ and $15.0{\pm}8.0%$ for 3-year DFS, p=0.010, $73.3{\pm}13.2%$ and $20{\pm}8.9%$ for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2909-2912
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• 2012

Aim: To evaluate efficacy and tolerability of topotecan treatment for recurrent small cell lung carcinoma. Patients and Methods: A total of 62 patients were evaluated retrospectively. Statistical analysis was performed using GraphPad Instat (version 3.05). Results: DFifty five of patients (89%) were male and 7 (11%) were female. Median age was $56.7{\pm}9.3$ (34-75). Forty eight of patients (80%) were extensive stage (ES) at the time of diagnosis. Fifty of the patients (80.6 Medical Oncology Clinic) were given median 5.36 cycles of cisplatin-etoposide (2-8 cycles). Time to recurrence was $15.6{\pm}6.13$ weeks in patients with limited stage (LS) and $6.3{\pm}3.82$ weeks in extensive stage (ES) (p<0.0001). Overall survival was $14.0{\pm}6.08$ months in ES and $17.9{\pm}6.88$ months in LS. The difference between two groups was statistically meaningful (p=0.0447). The overall survival of the patients was $14.8{\pm}6.43$ months (4.5-40 months). In terms of survival, there was no difference between males and females (p=0.1171). In 17 (27%) patients who were refractory to topotecan or in whom progression occurred other chemotherapies were used. Conclusion: Small cell lung cancer is chemosensitive, but recurrences occur in short time. Other chemotherapy regimens are used in progression. Topotecan is one of them. Patients who were young and in whom recurrences occur late had given better response to topotecan. Because of the retrospective nature of the study, we couldn't reach the records exactly and consequently, rate and duration of response couldn't be calculated. In recurrent SCLC topotecan is one of the treatment choices. But both hematological and non hematological side effects should be taken into consideration.

• Radiation Oncology Journal
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• v.31 no.4
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• pp.185-190
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• 2013

Purpose: We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). Materials and Methods: Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. Results: The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. Conclusion: We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.252-259
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• 2005

To clarify the clinicopathologic features of small-cell carcinomas (SCC) of the stomach, we reviewed three cases of surgically treated SCC. The first case was a pure SCC, with severe pancreatic invasion and peritoneal seeding. A gastro-jejunostomy was performed. Postoperative chemotherapy was performed with CDDP and VP-16 (8 cycles) but showed disease progression (PD); a consecutive chemotherapy with CDDP and irinotencan (2 cycles) also showed PD. A third line with CDDP, VP16, ifosfamide, and mesna was followed by a 4th line (CDDP and Taxol). The male patient died with liver metastasis and peritoneal seeding 14 months after the operation. The second case was a SCC mixed with a poorly differentiated adenocarcinoma. Profound lymphadenopathy and liver metastasis were found. Two cycles of preoperative chemotherapy with TS-1 and CDDP were performed, which showed nearly complete remission for lymphadenopathy and partial response for the primary tumor site and liver metastatic lesion. A total gastrectomy and extended lymphadenectomy was performed. There were no viable cancer cells in 35 retrieved lymph nodes. Postoperative chemotherapy using the same regimen was performed for 4 cycles. Enlarged liver metastasis was found at the follow-up CT scan, so a posterior segmentectomy of liver was performed. After liver surgery, the chemotherapy regimen was changed to irinotecan and cisplatin. This male patient has been in good health for the f4 months since gastric surgery. The third case was a pure SCC, and a subtotal gastrectomy was performed curatively. That male patient received 5 cycles of TS-1 and is still in good health 14 months after operation.

• Journal of Yeungnam Medical Science
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• v.23 no.2
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• pp.193-204
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• 2006

Purpose: Various postoperative adjuvant chemotherapy regimens have been proposed for the patients with advanced gastric cancer. The majority of clinical trials have shown no significant difference in the survival benefit. The aim of this study was to compare the survival rates of postoperative adjuvant chemotherapies used in stage III gastric cancer patients who received curative gastrectomy. Materials and Methods: Between 1990 and 1999, a survival analysis was performed in 260 patients who received curative gastric resection and postoperative adjuvant chemotherapy. The patients were divided into four groups according to the chemotherapeutic regimens received. The groups were: the F group: furtulon alone, FM group: furtulon and mitomycin, FAM group: 5-FU, adriamycin and mitomycin, FLEP group: 5-FU, leucovorin, etoposide and cisplatin. The survival rates were analyzed using the Kaplan-Meier method and the Cox proportional hazards model. Results: There were no differences among the groups of patients with regard to tumor characteristics except for lymph node metastasis and the ratio of metastasis to lymph nodes. In the FLEP group, the ratio of metastasis to lymph nodes was higher than in the other groups. The five and ten year survival rates of F, FM, FAM and FLEP were 51.9%, 28.9%, 59.5%, 49.8%, 66.1%, 57.4% and 30.0%, 27.5%, respectively. The univariate analysis showed that age, Borrmann type, lymph node metastasis, ratio of metastasis to lymph nodes, postoperative adjuvant chemotherapy and recurrence were significant factors for survival. For the multivariate analysis, recurrence, age, Borrmann type, ratio of lymph node metastasis and lymph node dissection were independent prognostic factors; however, the postoperative adjuvant chemotherapy was not an independent prognostic factor. Conclusion: The FAM regimen was the most beneficial postoperative adjuvant chemotherapy for improved survival rates; the FM regimen was the second and the FLEP regimen was the last. In order to determine the effectiveness of postoperative adjuvant chemotherapy in stage III gastric cancer, well designed prospective studies including a surgery only group will be needed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.101-104
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• 2016

Background: With advances in diagnostics and treatment approaches, patients with Hodgkin's lymphoma (HL) in developed countries can nowadays expect to have excellent outcomes. However, information about the characteristics and outcomes in the developing world is very scarce, and this is important given the fact that there are several reports about differences of disease characteristics depending on geographic location and the development level of the country. Materials and Methods: In this retrospective study we assessed the features of 36 adult (${\geq}18$ years old) patients with HL and their diagnosis and treatment and outcomes in the Clinic of Chemotherapy of Muratsan University Hospital of Yerevan State Medical University, Armenia, between 2008-2014. Results: All patients had classic HL and among them 19 (53%) had nodular sclerosis subtype, 8 (22%) mixed cellularity and 9 (25%) lymphocyte-rich. 16 (44.5%) patients were at stage II, 13 (36%) stage III and 7 (19.5%) stage IV. Median follow-up time was 24.5 months (range 1-71 months) and during the whole follow-up period only two relapses (early) were documented and there were no deaths. Twenty-three (64%) patients received a BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, and 13 (36%) ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) regimen. A total of 25 (69.5%) patients received radiation in addition to chemotherapy. Conclusions: Although the number of patients involved in the study is small and the median follow-up time was just two years, this retrospective study shows that treatment of HL can be successfully organized in a resource-limited setting.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.903-915
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• 1996

Background: Combination chemotherapy is now considered to be the cornerstone of small cell lung cancer (SCLC). management but the optimal management of limited SCLC is not well defined. The role of thoracic radiotherapy (TRT) is less well established. Recent meta-analyses reports revealed that TRT combined with chemotherapy produce "good" local control and prolonged survival. But other reports that survival was not changed. The liming, dose, volume and fractionation for TRT with the combined chemotherapy of SCLC remains unsettled. In this study, we analyzed the effects according to the timing of thoracic radiotherapy in limited SCLC. Method: All fifty one patients received cytoxan, adriamycin and vincristine(CAV) alternating with etoposide and cisplatin(VPP) every 3 weeks for 6 cycles were randomized prospectively into two groups: concurrent and sequential. 27 patients received 4500cGy in 30 fractions(twice daily 150cGy fractional dose) over 3 weeks 10 the primary site concurrent with the first cycle of VPP(concurrent gorup). 24 patients received 4000 to 5000cGy over 5 or 6 weeks after completion of sixth cycles of chemotherapy(sequential group). Results: 1. Response rates and response duration : Response rates were not significantly different between two groups(p=0.13). But response duration was superior in the concurrent group(p=0.03). 2. Survival duration was nor different between two groups(p=0.33). 3. Local control rate was superior in the concurrent group(p=0.00). 4. Side effects and toxicities: Hematologic toxicities, especially leukopenia, infection and frequency of radiation esophagitis were higher in the concurrent group (p=0.00, 0.03, 0.03). Conclusion: The concurrent use of TRT with chemotherapy failed to improve the survival of limited stage SCLC patients compared with the sequential use of TRT but response duration and local control rate were superior in the concurrent group. Frequency of radiation esophagitis, life threatening hematologic toxicities and infection were more frequent in the concurrent group than sequential group. So, the selection of an optimal schedule of chemotherapy combined with TRT that would lead to a major increase in survival with minimal toxicity is remained to be validated in large scale study in the future.

• Journal of Yeungnam Medical Science
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• v.31 no.2
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• pp.82-88
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• 2014

Background: Lung cancer is the most common cause of cancer-related death worldwide and in Korea, and small cell lung cancer (SCLC) is the most deadly tumor type in the different lung cancer histology. Chemotherapy is the main strategy of the treatment for SCLC, and etoposide and platinum regimen has been the only standard chemotherapy for about 30 years. To test feasibility of weekly divided dose irinotecan and carboplatin for Korean patients is the aim of this study. Methods: Patients with histologically or cytologically confirmed extensive stage SCLC were included. Patients with limited stage (LD), who could not tolerate concurrent chemoradiotherapy were also included. All the patients received irinotecan $60mg/m^2$, carboplatin 2 area under the curve at day 1, 8, and 15 every 4 weeks. Study regimen was discontinued when the disease progressed or intolerable side effects occurred. No more than 6 cycles of chemotherapy were given. Results: Total 47 patients were enrolled, among them 9 patients were LD. Overall response rate was 74.5% (complete response, 14.9%; partial response, 59.6%). Side effects greater than grade 3 were neutropenia (25.5%), fatigue (12.8%), thrombocytopenia (8.5%), sepsis (4.3%), and pancytopenia (2.1%). There was no treatment related death. Conclusion: Weekly divided irinotecan and carboplatin regimen is effective, and safe as a first line therapy for both stage of SCLC. Large scaled, controlled study is feasible.

• Archives of Pharmacal Research
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• v.27 no.1
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• pp.77-82
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• 2004

DA-125, a novel derivative of adriamycin, is known for its anti-cancer activity. In this study, the inhibitory mechanism of DA-125 on topoisomerase was investigated in the simian virus 40 (SV40) replicating CV-1 cell by studying the SV40 DNA replication intermediates and DNA-topoisomerase complexes. DNA-protein complexes that were formed in the drug-treated cells were quantitated by using a glass filter assay. SV40 DNA replication intermediates that were accumulated in the drug-treated CV-1 cell were analyzed in a high resolution gel. DA-125 did not accumulate B-dimers of SV40 DNA replication intermediates which were found in the adriamycin-treated CV-1 cells. DA-125 induced a dose-dependent formation of the DNA-protein complexes, while adriamycin did not. When adriamycin and etoposide (VP16) were added to the SV40-infected cells at the same time, adriamycin blocked the formation of the DNA-protein complexes induced by VP16 in a dose-dependent manner. However, DA-125 blocked the formation of the DNA-protein complexes induced by VP16 up to the maximum level of the DNA-protein complexes that were induced by DA-125 alone. Adriamycin and DA-125 did not inhibit the formation of the DNA-protein complexes that were caused by camptothecin, a known topoisomerase I poison. DA-125 is bifunctional in inhibiting topoisomerase II because it simultaneously has the properties of the topoisomerase II poison and the DNA intercalator. As a topoisomerase II poison, DA-125 alone induced dose-dependent formation of the DNA-protein complexes. However, as a DNA intercalator, it quantitatively inhibited the formation of the DNA-protein complexes induced by a strong topoisomerase II poison VP16. Furthermore considering that the levels of the DNA-protein complex induced by VP16 were decreased by DA-125 in terms of the topoisomerase II poison, we suggest that DA-125 has a higher affinity to the drug-binding sites of DNA than VP16 has.