• Archives of Plastic Surgery
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• 제43권6호
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• pp.491-497
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• 2016

Background Hypertrophic scarring is a pathological condition that occurs after trauma or surgery. Angiogenesis occurs more often with hypertrophic scarring than with normotrophic scarring. The regulation of angiogenesis is one of the key factors in hypertrophic scar management. Vascular endothelial growth factor (VEGF) is an essential factor in the angiogenetic response. This study investigated whether decreasing the level of VEGF is effective for treating hypertrophic scarring. Methods Ten 8-week-old female New Zealand white rabbits were included. Four defects were created on each ear by using a 6-mm punch. Bevacizumab (Avastin, Roche Pharma, Basel, Switzerland) was administered in one ear and normal saline was administered in the other ear. Treatment was administered starting on day 2, every 2 days, until day 14. The levels of VEGF were measured using enzyme-linked immunosorbent assay on day 10 and histologic results were analyzed on day 40. Results Bevacizumab induced-defects showed less hypertrophic scarring when compared with the control group as measured by the scar elevation index (SEI) and loose collagen arrangement. The SEI in the experimental group was $1.89{\pm}0.13$, compared to $1.99{\pm}0.13$ in the control group (n=30, P=0.005). Additionally, the VEGF level was lower ($38.72{\pm}11.03pg$ vs. $82.50{\pm}21.64pg$, n=10, P=0.001) and fewer vessels existed ($8.58{\pm}0.76$ vs. $7.2{\pm}1.20$, n=10, P=0.007). Conclusions Preventing excessive angiogenesis is effective for preventing scar formation, especially with hypertrophic scarring. Although it is not an approach that is sufficient alone for the management of scarring, it may be one of several important strategies for scar treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.253-256
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• 2014

Background: The standard treatment in the metastatic colorectal cancer consists of 5-FU based infusional regimens. However, with oral fluoropyrimidines, equal tumor responses may be obtained. Capecitabine causes macrocytosis of the cells by inhibition of DNA synthesis. In this context, a relationship was found between mean corpuscular volume (MCV) and response to therapy in breast cancer patients treated with Capecitabine, but whether this relationship also pertains in colorectal cancer has not been established. Materials and Methods: A total of 102 metastatic colorectal cancer patients treated with a oxaliplatin (XELOX)${\pm}$Bevacizumab combination were retrospectively evaluated. Patients were randomized into three groups. Hematological parameters (MCV, MPV, PCT, PLT, NLR) were recorded retrospectively, before treatment and after 3 cycles of chemotherapy. Results: After three cycles of therapy, 20 (19.6%) patients had progressive disease (PD), 41 (40.1%) had stable disease (SD), and 41 (40.1%) demonstrated a partial response (PR). In 62 (60.7%) treatment was with capesitabin plus XELOX therapy, and in 40 (39.2%) it was XELOX-Bevacizumab combination therapy. There was no difference among three groups before the treatment in terms of MCV, MPV, PCT, PLT, and NLR. MCV showed significant increase in chemotherapy response groups (PR and SD). In addition, a significant decrease was observed for platelet count in chemotherapy response groups. While NLR decrease was seen in only a PR group, PCT decrease was observed in all three groups. PCT and PLT values were higher in patients receiving Bevacizumab. Conclusions: PLT, PCT, MPV, and NLR values were decreased due to Capecitabine-based chemotherapy, however MCV was increased. PCT and PLT values were higher in patients who received Bevacizumab than those who did not. MCV, PLT, and NLR can be considered as important factors in predicting response to colorectal carcinoma treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6149-6154
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• 2015

Background: There is no suggested molecular indicator for the determination of which patients will benefit from anti-angiogenetic treatment in metastatic colorectal cancers. Materials and Methods: In this study, VEGF and $HIF-1{\alpha}$ expression and their clinical significance were studied in tumor tissues of patients with colorectal cancer receiving bevacizumab-based treatment. VEGF and $HIF-1{\alpha}$ were assessed by immunohistochemistry in the primary tumors of 53 metastatic colorectal cancer patients receiving chemotherapy in combination with first line bevacizumab. Results: The clinical benefit rate in the low-VEGF expression group was 38%, while it was 62% in the high expression group. While the median progression-free survival (PFS) was 10 months in the high-VEGF expression group, it was 8 months in the low-VEGF expression group (p = 0.009). The median overall survival (OS) was found to be 26 months vs 15 months. Thus, when VEGF was strongly expressed it was in favor of that group and the difference was statistically significant (p = 0.03). High VEGF expression rate was an independent factor that correlated with OS or PFS (p=0.016 and 0.009, respectively). Conclusions: The data showed that VEGF may have predictive value for determining the treatment of CRC.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.539-543
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• 2016

Background: It is well known that peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is associated with a poor prognosis. However, data on the prognostic significance of modern chemotherapy containing bevacizumab, cetuximab or panitumumab are not available. Materials and Methods: This retrospective review concerned 526 patients with metastatic CRC who were classified into two groups according to the presence or absence of PC, and were treated with systemic chemotherapy, with or without bevacizumab or anti-EGFR antibodies. The genetic background, in particular KRAS, BRAF, and PIK3CA gene mutations, and overall survival (OS) were compared between the two groups. Results: The median OS values were 23.3 and 29.1 months for PC and non-PC patients, respectively (hazard ratio [HR]=1.20; p=0.17). Among all patients, tumor location, number of metastatic sites and BRAF mutation status were significant prognostic factors, whereas the presence of PC was not. In the PC group, chemotherapy with bevacizumab resulted in a significantly longer OS than forchemotherapy without bevacizumab (HR=0.38, p<0.01), but this was not the case in the non-PC group (HR=0.80, p=0.10). Furthermore, the incidence of the BRAF V600E mutation was significantly higher in PC than in non-PC patients (27.7% versus 7.3%, p<0.01). BRAF mutations displayed a strong correlation with shorter OS in non-PC (HR=2.26), but not PC patients (HR=1.04). Conclusions: Systemic chemotherapy, especially when combined with bevacizumab, improved survival in patients with PC from CRC as well as non-PC patients. While BRAF mutation demonstrated a high frequency in PC patients, but it was not associated with prognosis.

• Journal of Digestive Cancer Research
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• 제2권2호
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• pp.52-55
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• 2014

The incidence of colorectal cancer (CRC) has continuously increased and CRC is a major cause of cancer-related death. Systemic chemotherapy has resulted in a significant improvement in overall survival in metastatic CRC. The development of biologic agents for the treatment of CRC has additionally expanded the options for the treatment. Cetuximab is useful in KRAS wild type tumors in combination with chemotherapy for metastatic disease in both the first and second line settings. It is also used as monotherapy after failure of both irinotecan and oxaliplatin containing regimens. Panitumumab has similar indications, and is primarily used in patients intolerant to cetuximab due to hypersensitivity reactions. Bevacizumab is primarily used as first line and second line therapy in metastatic CRC. However, the optimal way and duration to combine these chemotherapeutic agents are not yet established.

• Journal of Korean Neurosurgical Society
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• 제55권1호
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• pp.5-11
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• 2014

Objective : We evaluated pseudoprogression (PsPD) following radiation therapy combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse following anti-angiogenic therapy for patients with recurrent disease using the Response Assessment of the Neuro-Oncology Working Group. Methods : Patients who were pathologically confirmed as having high-grade glioma received radiotherapy with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11 were used as a salvage option for cases of radiologic progression. Magnetic resonance imaging (MRI) was routinely performed 1 month after concurrent radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the bevacizumab-containing regimen for progressive disease, MRI was performed every 2 months. Results : Of 55 patients, 21 (38%) showed radiologic progression within 4 weeks after CRT. Of these patients, 16 (29%) showed progression at second post-CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four initially non-progressed patients showed progression at the second post-CRT MRI (ltPD). No difference in survival was observed between the etPD and ltPD groups (p=0.595). Five (50%) of ten patients showed a radiological response after salvage bevacizumab therapy. Four of those patients exhibited rapid progression immediately after discontinuation of the drug (drug holiday). Conclusion : Twelve weeks following treatment could be the optimal timing to determine PsPD or true progression. MRI with gadolinium enhancement alone is not sufficient to characterize tumor response or growth. Clinical correlation with adequate follow-up duration and histopathologic validation may be helpful in discriminating PsPD from true progression.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.1059-1063
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• 2012

Objective: Angiogenesis represents a key element in the pathogenesis of malignancy. There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic colorectal cancer treated with vascular endothelial growth factor (VEGF)-targeted therapy. The present study was conducted to establish a prognostic model for patients using an oxaliplatin-based or irinotecan-based chemotherapy plus bevacizumab in metastatic colorectal cancer. Methods: Baseline characteristics and outcomes on 170 patients treated with FOLFIRI or XELOX plus anti-VEGF therapy-naive metastatic colorectal cancer were collected from three Turkey cancer centers. Cox proportional hazards regression was used to identify independent prognostic factors for OS. Results: The median OS for the whole cohort was 19 months (95% CI, 14.3 to 23.6 months). Three of the seven adverse prognostic factors according to the Anatolian Society of Medical Oncology (ASMO) were independent predictors of short survival: serum lactate dehydrogenase (LDH) greater than the upper limit of normal (ULN; p<0.001); neutrophils greater than the ULN (p<0.0014); and progression free survival (PFS) less than 6 months (p =0.001). Conclusion: Serum LDH and neutrophil levels were the main prognostic factors in predicting survival, followed by PFS. This model validates incorporation of components of the ASMO model into patient care and clinical trials that use VEGF-targeting agents.

• 대한안과학회지
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• 제60권2호
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• pp.144-151
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• 2019

목적: 당뇨황반부종 환자에서 항혈관성장인자의 유리체내주입술의 유효성과 안전성을 알아보고자 하였다. 대상과 방법: 연구목적에 부합하는 최근의 고품질의 체계적인 검토를 선정하였고, 선정된 문헌 고찰에 7건의 최근 수행된 무작위 임상시험을 추가하여 메타분석 및 네트워크 메타분석을 시행하였다. 유효성 결과 지표로는 1) 시력의 평균 향상, 2) 15글자 이상의 최대교정시력 개선을 경험한 환자의 비율, 3) 15글자 이상의 최대교정시력 저하를 경험한 환자의 비율을 파악하였고, 안전성 결과에는 전신이상 반응 및 안구 관련 이상 반응을 분석하였다. 결과: 라니비주맙과 베바시주맙의 교정시력의 평균 차이는 0.16 (95% confidence interval [CI]: -0.02, 0.345)이었고, 라니비주맙 대 애플리버셉트의 평균시력 차이는 -0.08 (95% CI: -0.26, 0.10)이었다. 치료 전후의 시력변화를 약제 간의 비교한 최대교정시력 변화지표에서 라니비주맙(-0.20; 95% CI: -0.40, -0.01)과 베바시주맙(-0.34; 95% CI: -0.53, -0.14)이 각각 애플리버셉트에 비해 효과가 낮은 것으로 나타났다. 전신 및 안구 부작용에서 약제 간에 유의한 차이가 없었다. 결론: 당뇨황반부종에서 애플리버셉트는 라니비주맙 또는 베바시주맙에 비하여 최대교정시력의 변화에 있어서 보다 효과적인 것으로 나타났다. 그러나 15글자 이상의 시력향상이나 시력저하에 있어서는 세 가지 약제에서 유의한 차이를 보이지 않았다. 항혈관성장인자의 안전성은 약제 간에 유의한 차이를 보이지 않았다.

• Journal of Gynecologic Oncology
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• 제29권6호
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• pp.96.1-96.12
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• 2018

The 3-weekly regimen of carboplatin and paclitaxel is the backbone of first line adjuvant chemotherapy for advanced ovarian cancer. The landmark Japanese Gynaecologic Oncology Group (JGOG) 3016 study demonstrated significant improvements in progression-free survival and overall survival with dose dense weekly administration of paclitaxel in combination with 3-weekly carboplatin. However, efforts to replicate these benefits have failed in subsequent phase III trials. Weekly paclitaxel is purported to have enhanced antitumor activity, with stronger anti-angiogenic effects, and yet is better tolerated. In this review, we explore the rationale for dose dense weekly paclitaxel, and compare the relevant trials as well as quality of life considerations. Possible reasons for the difference in outcomes between the JGOG 3016 and other studies are reviewed, with a focus on how the addition of bevacizumab, the variations between histological and molecular subtypes of epithelial ovarian cancers, and ethnic pharmacogenetic differences may potentially affect the efficacy of dose dense paclitaxel.

• 대한안과학회지
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• 제59권11호
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• pp.1039-1048
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• 2018

목적: 연령관련황반변성 환자에 대해 항혈관내피성장인자의 가능한 치료 방법에 따라 건강보험 재정에 미치는 영향을 분석하였다. 대상과 방법: 여러 치료 방법에 따른 건강보험 재정의 변화를 향후 5년(2018-2022년) 동안 추정하였다. 새로운 급여기준 이외 바이오시밀러 등장, 허가초과 비급여약제 사용 등을 고려한 시나리오에 대해서도 재정 영향을 분석하였다. 국민건강보험공단 청구자료 및 의료기관 자료를 기준으로 각 시나리오별로 향후 5년 동안 예상 진료환자 수, 치료 횟수를 추정하였으며, 재정부담을 추계하였다. 결과: 연령관련황반변성에서 현행의 사용형태로 기존 급여기준(평생 14회)이 유지되는 경우(시나리오 1) 2018년 기준 향후 5년간 보험소요재정은 약 4,403억 원으로 추정되었다. 2017년 12월에 변경된 급여기준하에서 5년간 보험소요재정은 약 5,601억 원으로 추정되었다. 2020년 이후 바이오시밀러 급여(시나리오 3), 현재 허가초과 비급여약제인 베바시주맙(시나리오 4)을 급여전환하는 경우에 각각 5,210억 원, 4,197억 원으로 예상되었다. 결론: 본 평생 14회라는 급여기준 삭제로 인해 건강보험 재정이 크게 증가할 것이 예상되었으나 실제 0.1 이하 그리고 반흔화/위축성 병변일 경우 급여 중단 등의 새로운 기준으로 중간폭으로 증가하는 것으로 나타났다. 또한 고령화로 인한 연령관련황반변성 유병환자의 증가를 고려할 때 바이오시밀러 및 베바시주맙 도입 등의 정책적 대안도 고려할 수 있다.