• Asian Pacific Journal of Cancer Prevention
• /
• 제14권4호
• /
• pp.2421-2427
• /
• 2013

Background: To study the response rate, toxicity profiles, and survival of refractory or recurrent epithelial ovarian cancer (EOC) patients treated with paclitaxel. Materials and Methods: Patients with refractory or recurrent EOC who were treated with paclitaxel between January 2002 and December 2011 at the Department of Obstetrics and Gynecology, Faculty of Medicine, Vajira Hospital were identified. Clinicopathological features of the patients including detailed data of paclitaxel treatment were collected. Results: During the study period, a total of 44 patients were identified, with a mean age of $52.9{\pm}8.2$ years. Some 13.6% (six patients) had refractory cancer to first-line chemotherapy while 86.4% (38 patients) had recurrent cancer. Among these, 35 (79.6%) and 9 (20.4%) patients were considered as platinum-sensitive and platinum-resistant, respectively. Three patients (6.8%) received fewer than 2 cycles of paclitaxel due to loss to follow-up, leaving 41 patients evaluable for response. The overall response rate observed in all 41 patients was 41.5% (17 patients; 12 complete and five partial responses): 12.5% or 1/8 patients with refractory or platinum-resistant cancer and 48.5% or 16/33 patients with platinum-sensitive disease. Stable disease was demonstrated in 17.0% (seven patients) while progressive disease was apparent in 41.5% (17 patients). Median time to progress was 4.5 months (range, 0.67-58.6 months). Median progression-free survival was not reached while median overall survival was 16.3 months (95% confidence interval, 11.0 months -21.6 months). Common toxicities were neutropenia, neuropathy, and alopecia. Conclusions: Paclitaxel is an active agent for refractory or recurrent EOC. Neutropenia, neuropathy and alopecia are common side effects.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권6호
• /
• pp.3711-3717
• /
• 2013

Background: To assess the efficacy and tolerability of Cisplatin plus Gemcitabine combination in patients with brain metastases (BM) from breast cancer (BC). Materials and Methods: Eighteen BC patients with BM who were treated with Cisplatin plus Gemcitabine regimen between 2003-2011 were evaluated. Results: A median of 6 cycles of this regimen were received, in fifteen patients (83.3%) as first-line chemotherapy, in 2 as second-line and in 1 as third-line after diagnosis of BM. Dose reduction was performed in 11 (61.1%) patients; major reasons were neutropenia and leukopenia. Grade III neutropenia and Grade II trombocytopenia rates were 33.3% and 16.7% respectively. Overall response rate (ORR; complete+partial response rate) was 33.4% (n=6) for the entire study population; triple negative patients achieved an 66.6% ORR while hormone receptor (HR) positive patients had 25% and HER2 positive patients 12.5%. Median progression-free survival was 5.6 months (2.4-8.8 months, 95%CI) and longer in patients with triple negative breast cancer (TNBC) (median 7.4 months, 95%CI, 2.4-12.3 months) than the patients with other subtypes (median 5 months for HER2 positive and 3.6 months for HR positive patients). Median PFS of the patients with TNBC who received this regimen as first-line was 9.2 months (5.2-13.2 months, 95%CI). Conclusions: Cisplatin plus Gemcitabine may be a treatment option for patients with BM from breast cancer. Longer PFS and higher response rates are results that support the usage of this regimen especially for the triple negative subtype. However, further prospective and randomized trials are clearly required to provide more exact information.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권20호
• /
• pp.8661-8666
• /
• 2014

Background: Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be one of the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limited its use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabine has been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimen with a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated in untreated patients with HER2-negative advanced gastric cancer. Materials and Methods: Fifty-four patients with HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients received docetaxel $60mg/m^2$ plus cisplatin $60mg/m^2$ (day 1) combined with capecitabine $1650mg/m^2$ (days 1-14) every 3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. Results: The median age was 54 years (range: 24-76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) had recurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD). The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with an overall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. At the median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients due to toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia, which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only in two cases. Conclusions: DCX regimen offers prominent anti-tumor activity and considered to be effective first-line treatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권7호
• /
• pp.3335-3341
• /
• 2014

Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean, $12.75{\mu}mol/L$) with compared to TA6/6 (mean, $9.92{\mu}mol/L$) with p<0.05. Conclusions: Our study support the conclusion that patients with a $UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the $UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권10호
• /
• pp.5177-5182
• /
• 2012

Purpose: To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitormonotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agent docetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC). Methods: We systematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standard second-line chemotherapy in previously treated advanced NSCLC. The end points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), 1-year survival rate (1-year SR) and grade 3 or 4 toxicities. The pooled hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis results showed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC in terms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI 0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall response rate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysis demonstrated that EGFR-TKI monotherapy significantly improved PFS (HR 0.73, 95%CI: 0.55-0.97, p=0.03) and ORR (RR 1.96, 95%CI: 1.46-2.63, p=0.000) in East Asian patients, but it did not translate into increase in OS and 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia and neutrotoxicity in EGFR-TKI monotherapy group, excluding grade 3 or 4 rash. Conclusion: Both interventions had comparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapy was associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFR-TKImonotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with standard second-line chemotherapy. These results should help inform decisions about patient management and design of future trials.

• 생명과학회지
• /
• 제21권11호
• /
• pp.1652-1657
• /
• 2011

혈액세포의 분화와 성장은 20 여종 이상의 성장인자에 의해 조절된다. 혈액세포 생산에 관여하는 인자를 조혈 성장인자(hematopoitic growth factor)라고 한다. 조혈성장인자를 임상적으로 사용하기 위해 원핵생물 또는 진핵 생물 생산 시스템에서 재조합 단백질로 생산되고 있다. 그 중에서 Glranulocyte-Colony Stimulating Factor(G-CSF)는 호중구 세포 수가 감소된 암환자와 선천성 질병을 가진 환자에게 임상적 치료제로 아주 중요한 역할을 한다. 이 환자들은 충분하지 못한 호중구 세포로 말미암아 감염에 대한 위험이 아주 높으며 치사율 또한 높다. 두 종류의 재조합 G-CSF가 항암치료 후 발생하는 부작용으로 나타나는 호중구 세포 감소증 치료에 사용되고 있다. G-CSF의 중요성에 맞추어 G-CSF의 물리적 및 생물학적 기능에 대한 특성을 설명하였으며, 또한 항암치료와 G-CSF의 임상적 사용에 대한 연관성을 토론하였다. 마지막으로 두 종류의 재조합 G-CSF인 non-glycosylated G-CSF, filgrastim과 glycosylated G-CSF를 비교 설명하였으며, 이들 기존의 G-CSF에 비교되는 바이오시밀러에 대한 전망을 제시하였다.

• 생명과학회지
• /
• 제21권12호
• /
• pp.1778-1783
• /
• 2011

조혈에 관여하는 cytokine은 골수세포의 성장과 분화를 촉진시켜 혈구세포 생산을 조절한다. 이런 cytokine을 조혈성장인자(hematopoitic growth factor)이라고 하고, 그 중에서 호중구 세포(neutrophil) 성장에 관여하는 과립구 콜로니 자극 인자(granulocyte-colony stimulating factor, G-CSF)는 임상적 치료제로서 아주 중요하다. 왜냐하면 화학적 항암치료를 받는 환자들에게 심각한 호중구 세포가 감소하는 증세(neutropenia)가 발생하여 감염으로 인한 사망이 일어나기 때문이다. 두 종류의 G-CSF 재조합 단백질이 치료제로 승인 받아 사용되고 있으며, G-CSF 재조합 단백질 생산에 대한 연구가 지속적으로 이루어지고 있다. 선행연구에서 본 연구팀은 누에에서 유래된 Bm5 세포주에서 G-CSF의 생산을 증대하기 위해 누에 prophenoloxidase activating enzyme의 Endoplasmic reticulum targeting signal sequence유전자와 사람 G-CSF 유전자를 융합한 chimera 유전자를 제작하여 재조합 G-CSF 단백질을 생산하였다. 본 연구에서는 이 chimera 유전자가 생산하는 재조합 G-CSF 단백질의 N-말단에 3 개의 아미노산이 결여되는 3 종류의 돌연변이 유전자를 제작하여 G-CSF 단백질 생산에 미치는 영향을 조사하였다. 그 중 한 돌연변이 유전자에 의해 세포 밖으로 분비된 G-CSF 단백질의 생산이 현저히 감소하여, N-말단 부분이 이 단백질의 분비에 관여한다는 것을 알 수 있었다.

• 병원약사회지
• /
• 제35권4호
• /
• pp.409-417
• /
• 2018

Background : Febrile neutropenia (FN) is one of the side effects in the patients treated with chemotherapy, and the patients who have FN generally need immediate treatment with extended-spectrum antibiotics and hospitalization. Pegfilgrastim and pegteograstim, which are used for the prevention of FN as a granulocyte-colony stimulating factor (G-CSF), have been granted insurance coverage in the Republic of Korea for certain breast cancer patients using doxorubicin and cyclophosphamide (AC) from September 2016. Methods : The data of the patients with breast cancer using AC regimen and G-CSF were collected retrospectively. This study involves cost-utility analysis of pegfilgrastim and pegteograstim. In this study, we constructed a simple decision tree model for short-term observation and calculated quality-adjusted life year (QALY) and the direct medical costs from the medical provider's perspective. Results : From September 2016 to May 2017, 15 patients were treated with pegfilgrastim and 15 patients were treated with pegteograstim. As a result of dividing the average cost by QALY for each treatment group, it was observed that pegfilgrastim and pegteograstim were consumed 24,923,384 won and 22,808,336 won per 1QALY, respectively. Consequently, incremental cost effectiveness ratio (ICER) showed 2,115,048 won more per pegfilgrastim than pegteograstim per 1QALY, and the cost per 1QALY of both the drugs was lower than 30,500,000 won; the Koreans were willing to pay this amount. Conclusions : This study suggests that pegfilgrastim and pegteograstim can be used to improve the quality of life of breast cancer patients undergoing AC therapy. Among the two drugs, pegteograstim seems to be more cost-effective. However, since this study was conducted as a retrospective observation method on a small scale, it is associated with many limitations. Therefore, a long-term prospective cohort study is needed to supplement the present findings.

• Genomics & Informatics
• /
• 제20권3호
• /
• pp.29.1-29.12
• /
• 2022

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3 and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III-IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of toxicity such as severe diarrhea or neutropenia.

• Pediatric Infection and Vaccine
• /
• 제31권1호
• /
• pp.83-93
• /
• 2024

목적: 코로나19 판데믹이 시작된 이후, 다양한 주요 변이 바이러스가 출현했다. 코로나 19 판데믹 기간 동안 대표적인 주요 변이 바이러스 유행 시기를 네 가지로 나누고, 네 가지의 주요 변이 바이러스 시기로부터 임상적 그리고 혈액학적 검사의 특징을 파악하고자 하였다. 방법: 코로나19 확진으로 입원한 19세 이하 환자의 의무기록을 후향적으로 분석하였다. 변이전시기(2020년 2월 1일-2020년 9월 30일), 알파와 베타 변이 시기(2020년 10월 1일-2021년 5월 31일), 델타 변이 시기(2021년 6월 1일-2021년 10월 31일), 오미크론 변이 시기(2021년 11월 1일-2022년 5월 31일)를 비교하였다. 결과:대상환자 827명중에서 163명(19.7%)가무증상이었고, 발열과기침의빈도는각각 320명(38.7%), 399명(48.2%)이었다. 38.5℃ 이상의 발열이 있었던 경우는 12세 미만인 경우에 오미크론 변이 시기에 높게 관찰되었다. 혈액학적 검사에서 백혈구 감소증, 임파구 감소증 그리고 호중구 감소증은 각각 33%, 30.2%, 24.9%로 관찰되었다. 결론: 코로나 19의 주요 변이 바이러스 우세 시기에 다른 특징들이 있었다. 델타 변이 시기에 4일 이상의 발열이 지속되는 경우가 더 많았고, 오미크론 변이 시기에는 38.5℃ 이상의 발열을 가지는 경우가 많았다.