• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5263-5267
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• 2013

Background: The aim of this study was to evaluate the efficacy and tolerability of a gemcitabine, 5-fluorouracil and leucovorin (GEMFUFOL) chemotherapy regimen as first line treatment of metastatic biliary tract cancer. Materials and Methods: All patients received folinic acid $400mg/m^2$ on day 1, 5-fluorouracil bolus $400mg/m^2$ on day 1, IV infusion of 5-fluorouracil $2400mg/m^2$ over 46 hours, and gemcitabine $1250mg/m^2$ on day 1. Results: A total of 29 patients with metastatic biliary tract cancer received GEMFUFOL regimen as the firstline treatment. The mean follow-up was 22.1 months (95%CI, 12.5-31.8). One patient (3.4%) achieved complete response, 5 (17.2%) had partial response, and 4 (13.8%) had stable disease. The median progression-free survival was 3.3 months (95%CI, 2.9-3.7), and the median overall survival was 8.8 months (95%CI, 3.5-14). The 1-year and 2-year survival rates were 58.6% and 30%, respectively. Grade 3 and 4 toxicity included neutropenia in 4 patients (13.7%), thrombocytopenia in 2 (6.8%), anemia2 (6.8%), and alopecia in 1 (3.4%). Two patients (6.8%) developed febrile neutropenia. A dose reduction was achieved in 8 patients (27.6%) while 5 patients had extended-interval dosage (17.2%) for toxicity. Conclusions: The GEMFUFOL chemotherapy regimen was generally efficacious and tolerable as a first-line treatment of metastatic biliary tract cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1123-1127
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• 2016

Chemotherapy is the primary treatment for advanced and recurrent cervical cancer. To evaluate the survival outcomes of chemotherapy and the prognostic factors in this setting, we conducted a retrospective study by reviewing the medical records of advanced and recurrent cervical cancer patients treated with systemic chemotherapy at our institute between January, 2008 and December, 2014. One hundred and seventy-three patients met the criteria with a mean age of 50.9 years. 4.1% of them were HIV positive. The most common initial stage was stage IVB (30.1%) and the most common histology was squamous cell carcinoma (68.6%). Ninety-two (53.2%) patients were previously treated with concurrent chemoradiation with 53% developing combined sites of recurrence. The median recurrence free interval was 16.7 months. Cisplatin + 5 fluorouracil (5FU) (53.2%) was the most frequent first line chemotherapy followed by carboplatin + paclitaxel (20.2%) with an objective response of 39.3%. Seventy-two patients received subsequent chemotherapy. The median overall survival of all studied patients was 13.2 months. Only a recurrence free interval of less than 12 months was an independent prognostic factor for survival outcome. In conclusion, chemotherapy treatment for advanced and recurrent cervical cancer patients showed modest efficacy with a shorter recurrence free survival less than 12 months as a significant poor prognosis factor.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.925-928
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• 2014

Background: Gestational trophoblastic neoplasia (GTN) is a spectrum of disease with abnormal trophoblastic proliferation. Treatment is based on FIGO stage and WHO risk factor scores. Patients whose score is 12 or more are considered as at extremely high risk with a high likelihood of resistance to first line treatment. Optimal therapy is therefore controversial. Objective: This study was conducted in order to summarize the regimen used for extremely high risk or resistant GTN patients in our institution the in past 10 years. Materials and Methods: All the charts of GTN patients classified as extremely high risk, recurrent or resistant during 1 January 2002 to 31 December 2011 were reviewed. Criteria for diagnosis of GTN were also assessed to confirm the diagnosis. FIGO stage and WHO risk prognostic score were also re-calculated to ensure the accuracy of the information. Patient characteristics were reviewed in the aspects of age, weight, height, BMI, presenting symptoms, metastatic area, lesions, FIGO stage, WHO risk factor score, serum hCG level, treatment regimen, adjuvant treatments, side effects and response to treatment, including disease free survival. Results: Eight patients meeting the criteria of extremely high risk or resistant GTN were included in this review. Mean age was 33.6 years (SD=13.5, range 17-53). Of the total, 3 were stage III (37.5%) and 5 were stage IV (62.5%). Mean duration from previous pregnancies to GTN was 17.6 months (SD 9.9). Mean serum hCG level was 864,589 mIU/ml (SD 98,151). Presenting symptoms of the patients were various such as hemoptysis, abdominal pain, headache, heavy vaginal bleeding and stroke. The most commonly used first line chemotherapeutic regimen in our institution was the VAC regimen which was given to 4 of 8 patients in this study. The most common second line chemotherapy was EMACO. Adjuvant radiation was given to most of the patients who had brain metastasis. Most of the patients have to delay chemotherapy for 1-2 weeks due to grade 2-3 leukopenia and require G-CSF to rescue from neutropenia. Five form 8 patients were still survived. Mean of disease free survival was 20.4 months. Two patients died of the disease, while another one patient died from sepsis of pressure sore wound. None of surviving patients developed recurrence of disease after complete treatment. Conclusions: In extremely high risk GTN patients, main treatment is multi-agent chemotherapy. In our institution, we usually use VAC as a first line treatment of high risk GTN, but since resistance is quite common, this may not suitable for extremely high risk GTN patients. The most commonly used second line multi-agent chemotherapy in our institution is EMA-CO. Adjuvant brain radiation was administered to most of the patients with brain metastasis in our institution. The survival rate is comparable to previous reviews. Our treatment demonstrated differences from other institutions but the survival is comparable. The limitation of this review is the number of cases is small due to rarity of the disease. Further trials or multicenter analyses may be considered.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.465-472
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• 2005

Background : The survival benefit associated with first-line chemotherapy in lung cancer has led to the need for second-line chemotherapy, for which Docetaxel ($Taxotere^{(R)}$) has proven efficacy in both settings. This study evaluated the safety and efficacy of docetaxel in patients with non-small cell lung cancer who had failed first-line platinum-based chemotherapy. Methods : Thirty one patients with non-small-cell lung cancer, who had failed first-line platinum-based chemotherapy, between March 1999 and August 2003, were enrolled in this study. Patients received intravenous docetaxel, either $75mg/m^2$ or $100mg/m^2$, with routine premedication every three weeks. Results : Fourteen patients (45.2%) had a partial response. The median survival and progression-free survival times were 12.5 months (95% CI 7.3-17.6) and 3.0 months (95% CI 1.6-4.5), respectively. This study showed 2 factors gave different survival benefits; the age (< 60 years: 20.1 months vs. ${\geq}60years$: 6.6 months, p = 0.0105) and the histological type (adenocarcinoma: 25.6 months vs. others: 7.9 months, p=0.0055). The predominant toxicity was neutropenia, which occurred as WHO grade 3 or 4 in 38.7 % of patients. One treatment-related death was also reported. Non-hematological toxicity was minor and easily controlled. There were no significant statistical differences in the survival benefit and toxicity between the two doses. Conclusion : Docetaxel, as second-line monotherapy, was well tolerated and effective in patients with non-small-cell lung cancer who failed first-line platinum-based chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2771-2774
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• 2012

Aim: Tumors of upper gastrointestinal tract are among the cancers that have a quite lethal course. Cytotoxic chemotherapy is the most efficient therapeutic modality for metastatic gastric cancer. In patients who do not respond to first-line treatment, the response rate to second-line therapies is generally low and the toxicity rates high. This study concerned the efficacy and the side effect profile of second-line therapy with irinotecan in the patients who were being followed-up with the diagnosis of metastatic gastric cancer in $\dot{I}$zmir, Turkey. Materials and Methods: We retrospectively evaluated the efficacy and toxicity in 31 patients with metastatic gastric adenocarcinoma who presented to the polyclinic of Medical Oncology of Izmir Ataturk Education and Research Hospital between May 2008 and July 2011. All received chemotherapy regimens containing cisplatin, fluoropyrimidine (5-FU) and docetaxel as the first-line therapy for late stage disease. Irinotecan as a single agent was given at a dose of 210 mg/$m^2$ on each 21 days. Irinotecan (180 mg/$m^2$ on day 1), 5-FU (500 mg/$m^2$ on days 1-2) and leucovorin (LV; 60 mg/$m^2$ on days 1-2) as a combined regimen were given over a 14 day period. Results: Median age was 54 (range, 31-70). Irinotecan was given as a combined regimen for median 6 cycles (range, 3-12) and as a single agent for median 3 cycles (range, 1-10). Metastases were detected in one site in six patients (19%), in two different sites in 17 patients (55%) and in three or more sites in eight patients (26%). Four patients (12.9%) showed partial response and six patients (19.3%) showed stable disease. Progression-free survival (PFS) was found to be 3.26 months (95% CI, 2.3-4.2). Median overall survival (OS) was found to be 8.76 months (95% CI, 4.5-12.9). The most commonly seen grade 3/4 side effect was neutropenia but the the therapy was generally well-tolerated. Conclusions: In this study, it was demonstrated that second-line therapy with irinotecan given following the first-line therapy with cisplatin, fluoropyrimidine (5-FU) and docetaxel was efficient and safe. Further studies are needed for confirmation.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6517-6521
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• 2012

To analyze the growth, proliferation, apoptosis, invasiveness and chemotherapy sensitivity of EC9706 cells after K-Ras gene silencing, an expression carrier pSilencer-siK-Ras was constructed, and the EC9706 cell line was transfected using a liposome technique. Six groups were established: Control, siRNA NC (transfected with empty vector pSilencer2.1); Ras siRNA (transfected with pSilencer-siK-Ras2); Paclitaxel; Paclitaxel + siRNA NC; and Ras siRNA + Paclitaxel. After the treatment, RT-PCR, Western blotting, MTT assay, flow cytometry and the Transwell technique were used to assess expression of K-Ras mRNA and protein in EC9706 cells, as well as cell growth, proliferation, apoptosis and invasiveness. The effect of Paclitaxel chemotherapy was also tested. pSilencer-siK-Ras2 effectively down-regulated expression of K-Ras mRNA and protein in EC9706 cells, growth being significantly inhibited. Flow cytometry indicated obvious apoptosis of cells in the experimental group, with arrest in the G1 phase; cell migration ability was also reduced. After pSilencer-siK-Ras2 transfection or the addition of Paclitaxel, EC9706 cells were suppressed to different extents; the suppressive effect was strengthened by combined treatment. The results suggested that RNAi-induced K-Ras gene silencing could enhance chemotherapy sensitivity of esophageal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6001-6006
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• 2015

Background: Pancreatic cancer is the fourth leading cause of cancer related death with median survival ranging from 3 to 6 months for metastatic disease. Palliative chemotherapy has been the backbone of treatment in advanced stage and has evolved over time. Data pertaining to the disease are scarce from our part of the world where treatment poses a significant challenge due to lack of resources. Materials and Methods: A retrospective chart review was performed for all patients presenting with stage IV pancreatic carcinoma at a tertiary care hospital in Karachi, Pakistan between January 2008 and December 2012. Data were collected using a pre-designed, coded questionnaire looking at patient characteristics, treatment given and outcome. Results: 101 patients were found to be eligible. Mean age was $56.7{\pm}12.8years$, the male to female ratio was 2:1 and most patients had a good performance status. More than half of the tumors were located in the head (57%, n=58) and almost all were adenocarcinomas (95%, n=96). Some 58% (n=59) received first line chemotherapy of which 49% (n=29) received gemcitabine-based regimens and 39% (n=23) received FOLFIRINOX. The median progression free survival for gemcitabine based treatment was 2.9 months (IQR=1.6-5.6) as opposed to 7.3 months (IQR=4.5-9.2) for FOLFIRINOX (P=0.02). Median overall survival was 4.9 months (IQR=2.3-9.5) for first line gemcitabine based treatment and 10.5 months (IQR=7.0-13.2) for first line FOLFIRINOX therapy (P=0.002). Patients on FOLFIRINOX had better survival across all subgroups. Inpatient admissions and dose reductions were more frequent with FOLFIRINOX but the difference between the two regimens was not statistically significant. FOLFIRINOX could be successfully administered as outpatient therapy to a number of patients. Conclusions: FOLFIRINOX remains a suitable first line option in patients with metastatic pancreatic cancer with good performance status even in a resource-poor country where diagnostic and supportive care facilities may be less than optimal and cost is a limitation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.831-835
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• 2014

Background: Predictor factors determining complete response to treatment are still not clearly defined. We aimed to evaluate clinicopathological features, risk factors, treatment responses, and survival analysis of patient with advanced nonseminomatous GCTs (NSGCTs). Materials and Methods: Between November 1999 and September 2011, 140 patients with stage II and III NSGCTs were referred to our institutions and 125 patients with complete clinical data were included in this retrospective study. Four cycles of BEP regimen were applied as a first-line treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with autologous stem cell transplantation were given in patients who progressed after BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients with incomplete radiographic response and normal tumor markers. Results: The median age was 28 years. For the good, intermediate and poor risk groups, compete response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion were associated with worse outcomes. There were 32 patients (25.6%) with non-CR who were treated with salvage treatment. Thirty-one patients died from GCTs and 94% of them had stage III disease. Conclusions: Even though response rates are high, some patients with GCTs still need salvage treatment and cure cannot be achieved. Non-complete response to platinium-based first-line treatment is a negative prognostic factor. Our study confirmed the need for a prognostic and predictive model and more effective salvage approaches.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5941-5944
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• 2014

Purpose: To highlight the potential factors that could predict the response rate of patients with metastatic colorectal cancer (mCRC) treated with pemetrexed combined chemotherapy after first- or second-line chemotherapy using the FOLFOX regimen. Materials and Methods: Between January 2007 and July 2014, 54 patients diagnosed and pathologically-confirmed with advanced colorectal cancer in Jiangsu Cancer Hospital and Research Institute, were enrolled. They received pemetrexed at a dose of $500mg/m^2$ by 10 minute infusion on day 1, repeated every 3 weeks. Doses were modified depending on nadir counts of blood cells. Combined chemotherapeutic agents included irinotecan, lobaplatin, carboplatin, oxaliplatin, gemcitabine, cis-platinum or bevacizumab. Multiple variables (age, sex, hemoglobin, platinum drugs combined, metastasis sites, LDH, ALP, CEA>40 ug/ml) reported earlier were selected. We used logistic regression analysis to evaluate relationships between these and tumor response. Results: On multivariable analysis, we found that age was significant in predicting the responsiveness to pemetrexed (p<0.05) combined with oxaliplatin. We did not find any other factors which were significantly associated with the response rate to chemotherapy with pemetrexed and irinotecan. Conclusions: By multivariate analysis, we found that age had significant impact on the responsiveness of pemetrexed when combined with oxaliplatin. Additional research based on genomic properties of host and tumors are needed to clarify markers for better selection of patients who could benefit from pemetrexed combined chemotherapy.