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Purpose@#To provide a wider choice of treatment opportunities for patients with neuroendocrine tumor (NET) in Korea, we have conducted a phase 1, open-label, single-arm, dose-escalation study of SNU-KB-01, a no-carrier added (NCA) 177Lu-labeled DOTATATE. @*Materials and Methods@#Seven patients with inoperable, progressive, metastatic, or locally advanced, somatostatin receptor-positive NET with Ki67 index ≤ 20% were enrolled according to the rolling six design. The study consisted of two cohorts to receive 4 cycles of SNU-KB-01 every 8 weeks for the first dose of 5.55 GBq (n=3) and 7.40 GBq (n=4). We assessed the incidence of dose-limiting toxicity (DLT) and adverse event, absorbed dose of kidneys and bone marrow, and objective tumor response. @*Results@#Seven patients completed 4 cycles (21.3-30.1 GBq total dose) of SNU-KB-01. The mean absorbed doses to kidneys and bone marrow were 0.500 mGy/MBq and 0.053 mGy/MBq, respectively, and the total body effective dose was 0.115 mSv/MBq. No DLT was observed and the maximum tolerated dose was 7.40 GBq/cycle. Grade 3 thrombocytopenia occurred in one patient, but no other grade 3 or 4 major hematologic or renal toxicity was observed. The best objective response to SNU-KB-01 was partial response. Overall response rate was 42.9% and disease control rate was 85.7%. @*Conclusion@#Treatment with 4 cycles of SNU-KB-01 was well tolerated and resulted in control of disease in most of the patients. Our results indicate SNU-KB-01, an NCA 177Lu-labeled DOTATATE, as a potentially safe and efficacious treatment option for NET patients in Korea.
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Plasma circulating tumor DNA (ctDNA) sequencing has demonstrated clinical utility for tumor molecular profiling at initial diagnosis or tumor progression in advanced solid cancers and is being rapidly incorporated into the clinical practice guidelines, including non–small cell lung and breast cancer. Despite relatively low sensitivity, plasma ctDNA sequencing has several advantages over tissue-based assays, including ease of sampling, rapid turnaround time, repeatability, and the ability to overcome spatial heterogeneity, which makes it ideal for investigating acquired resistance and monitoring tumor evolution and dynamics. With technological advancement and declining costs, the clinical application of plasma ctDNA is expanding, and numerous ongoing clinical trials are examining its potential to guide the management of advanced, localized, and even preclinical cancers of various tumor types. The ability of plasma ctDNA analysis to detect minimal residual disease following curative treatment in the absence of clinical disease is among its most promising attributes. Plasma ctDNA sequencing can also facilitate the conduct of clinical trials and drug development, particularly in immunotherapy. In order to incorporate plasma ctDNA sequencing for clinical decision-making, it is important to understand the preanalytical and analytical factors that may affect its sensitivity and reliability.
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Purpose@#This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer. @*Materials and Methods@#Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events. @*Results@#A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%). @*Conclusion@#This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.
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Purpose@#Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib. @*Materials and Methods@#In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease were sequenced using a targeted next-generation sequencing platform which included 106 genes. @*Results@#A total of 285 blood samples from 110 patients were analyzed. Higher baseline cfDNA concentration was associated with worse progression-free survival (PFS) and overall survival (OS). After 2 cycles of treatment, variant allele frequency (VAF) in the majority of ctDNA mutations decreased with a mean relative change of –31.6%. Decreases in the VAF of TP53, APC, TCF7L2, and ROS1 after 2 cycles of regorafenib were associated with longer PFS. We used the sum of VAF at each time point as a surrogate for the overall ctDNA burden. A reduction in sum (VAF) of ≥ 50% after 2 cycles was associated with longer PFS (6.1 vs. 2.7 months, p=0.002), OS (11.3 vs. 5.9 months, p=0.001), and higher disease control rate (86.3% vs. 51.1%, p < 0.001). VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly. @*Conclusion@#Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib.
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Objective@#To determine the impact of dedicated subspecialized radiologists in multidisciplinary team (MDT) discussions on the management of lower gastrointestinal (GI) tract malignancies. @*Materials and Methods@#We retrospectively analyzed the data of 244 patients (mean age ± standard deviation, 61.7 ± 11.9 years) referred to MDT discussions 249 times (i.e., 249 cases, as five patients were discussed twice for different issues) for lower GI tract malignancy including colorectal cancer, small bowel cancer, GI stromal tumor, and GI neuroendocrine tumor between April 2018 and June 2021 in a prospective database. Before the MDT discussions, dedicated GI radiologists reviewed all imaging studies again besides routine clinical reading. The referring clinician’s initial diagnosis, initial treatment plan, change in radiologic interpretation compared with the initial radiology report, and the MDT’s consensus recommendations for treatment were collected and compared. Factors associated with changes in treatment plans and the implementation of MDT decisions were analyzed. @*Results@#Of the 249 cases, radiologic interpretation was changed in 73 cases (29.3%) after a review by dedicated GI radiologists, with 78.1% (57/73) resulting in changes in the treatment plan. The treatment plan was changed in 92 cases (36.9%), and the rate of change in the treatment plan was significantly higher in cases with changes in radiologic interpretation than in those without (78.1% [57/73] vs. 19.9% [35/176], p < 0.001). Follow-up records of patients showed that 91.2% (227/249) of MDT recommendations for treatment were implemented. Multiple logistic regression analysis revealed that the nonsurgical approach (vs. surgical approach) decided through MDT discussion was a significant factor for patients being managed differently than the MDT recommendations (odds ratio, 4.48; p = 0.017). @*Conclusion@#MDT discussion involving additional review of radiology examinations by dedicated GI radiologists resulted in a change in the treatment plan in 36.9% of cases. Changes in treatment plans were significantly associated with changes in radiologic interpretation.
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Purpose@#We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients. @*Materials and Methods@#This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled. @*Results@#A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction. @*Conclusion@#This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.
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Purpose@#Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed. @*Materials and Methods@#Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety. @*Results@#Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia. @*Conclusion@#Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.
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PURPOSE: This study was designed to identify novel fusion transcripts (FTs) and their functional significance in colorectal cancer (CRC) lines. MATERIALS AND METHODS: We performed paired-end RNA sequencing of 28 CRC cell lines. FT candidates were identified using TopHat-fusion, ChimeraScan, and FusionMap tools and further experimental validation was conducted through reverse transcription-polymerase chain reaction and Sanger sequencing. FT was depleted in human CRC line and the effects on cell proliferation, cell migration, and cell invasion were analyzed. RESULTS: One thousand three hundred eighty FT candidates were detected through bioinformatics filtering. We selected six candidate FTs, including four inter-chromosomal and two intrachromosomal FTs and each FT was found in at least one of the 28 cell lines. Moreover, when we tested 19 pairs of CRC tumor and adjacent normal tissue samples, NFATC3–PLA2G15 FT was found in two. Knockdown of NFATC3–PLA2G15 using siRNA reduced mRNA expression of epithelial–mesenchymal transition (EMT) markers such as vimentin, twist, and fibronectin and increased mesenchymal–epithelial transition markers of E-cadherin, claudin-1, and FOXC2 in colo-320 cell line harboring NFATC3–PLA2G15 FT. The NFATC3–PLA2G15 knockdown also inhibited invasion, colony formation capacity, and cell proliferation. CONCLUSION: These results suggest that that NFATC3–PLA2G15 FTs may contribute to tumor progression by enhancing invasion by EMT and proliferation.
Subject(s)
Humans , Cadherins , Cell Line , Cell Movement , Cell Proliferation , Claudin-1 , Colorectal Neoplasms , Computational Biology , Fibronectins , RNA , RNA, Messenger , RNA, Small Interfering , Sequence Analysis, RNA , VimentinABSTRACT
PURPOSE: Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC). MATERIALS AND METHODS: Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m² plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m² twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity. RESULTS: From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation. CONCLUSION: Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.
Subject(s)
Humans , Apoptosis , Arm , Bevacizumab , Capecitabine , Cellular Senescence , Colorectal Neoplasms , Creatine Kinase , Disease-Free Survival , Drug Therapy , Follow-Up Studies , Liver , Simvastatin , Tablets , Treatment OutcomeABSTRACT
PURPOSE: The purpose of this study was to evaluate treatment response to neoadjuvant chemoradiotherapy (CRT) with regard to mucin status in pathology and pretreatment magnetic resonance imaging (MRI) in locally advanced rectal cancer. MATERIALS AND METHODS: Between 2003 and 2011, 306 patients with locally advanced rectal cancer received neoadjuvant CRT followed by surgery, and mucinous adenocarcinoma (MAC) was found in 27 (8.8%). All MAC patients had MRI before and after CRT and mucin proportion at MRI was measured. Therapeutic response was assessed by pathology after total mesorectal excision. To determine the optimal cut-off for mucin proportion in predicting good CRT response (near total or total regression) and negative circumferential resection margin (CRM), the receiver-operating characteristic analysis was performed. RESULTS: After neoadjuvant CRT, overall downstaging occurred in 44.4% of MAC and 72.4% of non-MAC (p=0.001), and positive CRM (≤1 mm) was observed more frequently in MAC (p<0.001). The optimal threshold for treatment response was 30% for mucin proportion, and there are nine with low mucin proportion (<30%) and 18 with high mucin proportion (≥30%) in pretreatment MRI. Negative CRM and tumor downstaging occurred more common in patients with mucin <30%, although statistically insignificant (p=0.071 and p=0.072, respectively). Regarding oncologic outcomes, lower mucin proportion in pretreatment MRI was associated with better disease-free and overall survival in MAC group (p=0.092 and 0.056, respectively), but the difference did not reach statistical significance. CONCLUSION: Poor treatment outcome with neoadjuvant CRT was observed in patients with MAC, especially those with high mucin proportion at pretreatment MRI.
Subject(s)
Humans , Adenocarcinoma, Mucinous , Chemoradiotherapy , Magnetic Resonance Imaging , Mucins , Pathology , Rectal Neoplasms , Treatment OutcomeABSTRACT
PURPOSE: Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors. MATERIALS AND METHODS: Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort. RESULTS: A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse eventswere diarrhea,rash, stomatitis, pruritus, and anorexia. Dose-limiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD ≥ 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer). CONCLUSION: Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.
Subject(s)
Humans , Anorexia , Appointments and Schedules , Breast Neoplasms , Carcinoma, Non-Small-Cell Lung , Cohort Studies , Diarrhea , Epithelial Cells , In Vitro Techniques , Lung , Maximum Tolerated Dose , Pharmacokinetics , Phosphotransferases , Protein-Tyrosine Kinases , Pruritus , ErbB Receptors , Stomach Neoplasms , Stomatitis , TyrosineABSTRACT
PURPOSE: Patients treated with anticancer agents often experience a variety of treatment-related skin problems, which can impair their quality of life. MATERIALS AND METHODS: In this cross-sectional study, Dermatology Life Quality Index (DLQI) and clinical information were evaluated in patients under active anticancer treatment using a questionnaire survey and their medical records review. RESULTS: Of 375 evaluated subjects with anticancer therapy, 136 (36.27%) and 114 (30.40%) were treated for breast cancer and colorectal cancer, respectively. We found that women, breast cancer, targeted agent use, and longer duration of anticancer therapy were associated with higher dermatology-specific quality of life distraction. In addition, itching, dry skin, easy bruising, pigmentation, papulopustules on face, periungual inflammation, nail changes, and palmoplantar lesions were associated with significantly higher DLQI scores. Periungual inflammation and palmoplantar lesions scored the highest DLQI. CONCLUSION: We believe our findings can be helpful to clinicians in counseling and managing the patients undergoing anticancer therapy.
Subject(s)
Female , Humans , Antineoplastic Agents , Breast Neoplasms , Colorectal Neoplasms , Counseling , Cross-Sectional Studies , Dermatology , Drug-Related Side Effects and Adverse Reactions , Inflammation , Medical Records , Pigmentation , Pruritus , Quality of Life , SkinABSTRACT
PURPOSE: FDG PET is effective in treatment response evaluation of cancer. However, there is no standard method for quantitative evaluation of FDG PET, particularly regarding cytostatic drugs. We compared various FDG PET quantitative methods in terms of response determination.METHODS: A total of 39 refractory metastatic colorectal cancer patients who received a multikinase inhibitor treatment were included. Baseline and posttreatment FDG PET/CT scans were performed before and two cycles after treatment. Standardized uptake value (SUV) and total lesion glycolysis (TLG) values using various margin thresholds (30–70 % of maximum SUV with increment 10 %, twice mean SUV of blood pool, SUV 3.0, and SUV 4.0) were measured, with measurement target of the hottest lesion or a maximum of five hottest lesions. Treatment response by the PERCIST criteria was also determined. Predictive values of the PET indexes were evaluated in terms of the treatment response determined by the RECIST 1.1 criteria.RESULTS: The agreement rate was 38 % between response determined by the PERCIST and the RECIST criteria (κ = 0.381). When patients were classified into disease control group (PR, SD) and non-control group (PD) by the RECIST criteria, percent changes of TLG with various margin thresholds (particularly, 30–50%of maximum SUV) exhibited significant differences between the two groups, and high diagnostic power for the response by the RECIST criteria. TLG-based criteria, which used a margin threshold of 50 % of maximum SUV, exhibited a high agreement with the RECIST criteria compared with the PERCIST criteria (κ = 0.606).CONCLUSION: In metastatic colorectal cancer, FDG PET/CT could be effective for treatment response evaluation by using TLG measured by margin thresholds of 30–50%of maximum SUV. Further studies are warranted regarding the optimal cutoff values for this method.
Subject(s)
Humans , Colorectal Neoplasms , Cytostatic Agents , Evaluation Studies as Topic , Fluorodeoxyglucose F18 , Glycolysis , Methods , Positron-Emission Tomography , Positron Emission Tomography Computed Tomography , Response Evaluation Criteria in Solid TumorsABSTRACT
PURPOSE: Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)–positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients. MATERIALS AND METHODS: This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment history were extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity. RESULTS: The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated. CONCLUSION: Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.
Subject(s)
Female , Humans , Administration, Oral , Breast Neoplasms , Breast , Disease Progression , Disease-Free Survival , Korea , Multivariate Analysis , Retrospective StudiesABSTRACT
PURPOSE: KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo. MATERIALS AND METHODS: The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects. RESULTS: KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho-Src and proliferative-signaling molecules were down-regulated in KX-01-sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01-induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01-sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model. CONCLUSION: KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.
Subject(s)
Animals , Mice , Aneuploidy , Breast Neoplasms , Cell Cycle , Cell Cycle Checkpoints , Cell Line , Fluorescent Antibody Technique , Heterografts , In Vitro Techniques , Microtubules , Mitosis , src-Family Kinases , Triple Negative Breast Neoplasms , Tubulin , Wound HealingABSTRACT
PURPOSE: This study aimed to evaluate the efficacy and safety of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy beyond standard treatment for anthracycline- and taxane-pretreated metastatic breast cancer (MBC). METHODS: We consecutively enrolled 158 MBC patients who underwent CMF chemotherapy in a palliative setting at two academic hospitals in Korea between 2002 and 2016. RESULTS: The median age of the 158 enrolled patients was 51 years (range, 30–77 years). The enrolled patients were treated with a median of 5 lines of systemic treatment (range, 2–11) before CMF therapy, and the median time from diagnosis of MBC to CMF administration was 36.0 months (range, 7.1–146.7 months). The median number of cycles of CMF treatment was 3 (range, 1–19), and the relative dose intensity was 90.4%. The toxicity profile was mild, with an observed 3.1% of grade 2 and 5.0% of grade 3/4 neutropenia. Among 147 patients (93.0%) whose response to CMF was evaluated, the response rate was 10.9% (16/147), with complete response (CR) in one and partial response (PR) in 15. In addition, the disease control rate (calculated as CR+PR+stable disease) was 44.2% (65/147). The median progression-free survival and overall survival were 3.1 months (95% confidence interval [CI], 2.7–3.6) and 9.4 months (95% CI, 7.1–11.6), respectively. CONCLUSION: CMF therapy is effective and tolerable as salvage treatment for heavily pretreated MBC.
Subject(s)
Humans , Breast Neoplasms , Breast , Cyclophosphamide , Diagnosis , Disease-Free Survival , Drug Therapy , Fluorouracil , Korea , Methotrexate , Neutropenia , Palliative Care , Retrospective Studies , Salvage TherapyABSTRACT
PURPOSE: The purpose of this study was to assess current levels of awareness of clinical trials (CTs), perceptions regarding their benefits and willingness to participate to CTs among Korean cancer patients. MATERIALS AND METHODS: From December 2012 to August 2015, we distributed questionnaires to cancer patients receiving systemic anti-cancer therapy at Seoul National University Hospital, Seoul, Korea. RESULTS: A total of 397 out of 520 requested patients (76.3%) responded to the survey. Among the 397 patients, 62.5% were female and the median age was 52 years. Overall, 97.4% (387/397) answered that they have at least heard of CTs. When asked about their level of awareness, 23.8% (92/387) answered that they could more than roughly explain about CTs. The average visual analogue scale score of CT benefit in all patients was 6.43 (standard deviation, 2.20). Patients who were only familiar with the term without detailed knowledge of the contents had the least expectation of benefit from CTs (p=0.015). When asked about their willingness to participate in CTs, 56.7% (225/397) answered positively. Patients with higher levels of awareness of CTs showed higher willingness to participate (p < 0.001). Heavily treated patients and patients with previous experience regarding CTs also showed a higher willingness to participate (p < 0.001). The perceived benefit of CTs was higher in the group willing to participate (p=0.026). CONCLUSION: The patient’s level of awareness regarding CTs was positively related to the positive perception and willingness to participate. Although the general awareness of CTs was high, a relatively large proportion of patients did not have accurate knowledge; therefore, proper and accurate patient education is necessary.
Subject(s)
Female , Humans , Korea , Patient Education as Topic , Seoul , VolitionABSTRACT
PURPOSE: RNA editing generates protein diversity by altering RNA sequences in coding regions without changing the overall DNA sequence. Adenosine-to-inosine (A-to-I) RNA editing events have recently been reported in some types of cancer, but they are rare in human colorectal cancer (CRC). Therefore, this study was conducted to identify diverse RNA editing in CRC. MATERIALS AND METHODS: We compared transcriptome data of 39 CRC samples and paired adjacent tissues from The Cancer Genome Atlas database to identify RNA editing patterns in CRC, focusing on canonical A-to-I RNA edits in coding sequence regions. We investigated nonsynonymous RNA editing patterns by comparing tumor and normal tissue transcriptome data. RESULTS: The number of RNA edits varied from 12 to 42 per sample. We also observed that hypoand hyper-RNA editing patterns were distinguishable within the samples. We found 10 recurrent nonsynonymous RNA editing candidates in nine genes (PDLIM, NEIL1, SRP9, GLI1, APMAP, IGFBP7, ZNF358, COPA, and ZNF587B) and validated some by Sanger sequencing and the inosine chemical erasing assay. We further showed that editing at these positions was performed by the adenosine deaminase acting on RNA 1 enzyme. Most of these genes are hypoedited in CRC, but editing of GLI1 was increased in cancer tissues compared with normal tissues. CONCLUSION: Our results show that nonsynonymous RNA editing patterns can be used to identify CRC patients and could serve as novel biomarkers for CRC.
Subject(s)
Humans , Adenosine Deaminase , Base Sequence , Biomarkers , Clinical Coding , Colorectal Neoplasms , Genome , Inosine , RNA Editing , RNA , TranscriptomeABSTRACT
PURPOSE: Although combining aromatase inhibitors (AI) with gonadotropin-releasing hormone agonists (GnRHa) is becoming more common, it is still not clear if GnRHa is as effective as bilateral salpingo-oophorectomy (BSO). MATERIALS AND METHODS: We retrospectively analyzed data of 66 premenopausal patients with hormone receptor– positive, human epidermal growth factor receptor 2–negative recurrent and metastatic breast cancer who had been treated with AIs in combination with GnRHa or BSO between 2002 and 2015. RESULTS: The median patient age was 44 years. Overall, 24 (36%) received BSO and 42 (64%) received GnRHa. The clinical benefit rate was higher in the BSO group than in the GnRHa group (88% vs. 69%, p=0.092). Median progression-free survival (PFS) was longer in the BSO group, although statistical significance was not reached (17.2 months vs. 13.3 months, p=0.245). When propensity score matching was performed, the median PFS was 17.2 months for the BSO group and 8.2 months for the GnRHa group (p=0.137). Multivariate analyses revealed that the luminal B subtype (hazard ratio, 1.67; 95% confidence interval [CI], 1.08 to 2.60; p=0.022) and later-line treatment (≥ third line vs. first line; hazard ratio, 3.24; 95% CI, 1.59 to 6.59; p=0.001) were independent predictive factors for a shorter PFS. Incomplete ovarian suppression was observed in a subset of GnRHa-treated patients whose disease showed progression, with E2 levels higher than 21 pg/mL. CONCLUSION: Both BSO and GnRHa were found to be effective in our AI-treated premenopausal metastatic breast cancer patient cohort. However, further studies in larger populations are needed to determine if BSO is superior to GnRHa.
Subject(s)
Female , Humans , Aromatase Inhibitors , Aromatase , Breast Neoplasms , Breast , Cohort Studies , Disease-Free Survival , Gonadotropin-Releasing Hormone , Multivariate Analysis , Ovariectomy , Phenobarbital , Premenopause , Propensity Score , ErbB Receptors , Retrospective StudiesABSTRACT
PURPOSE: While tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) can aid in the diagnosis of biliary tract cancer, their prognostic role has not been clearly elucidated. Therefore, this study was conducted to evaluate the prognostic role of tumor markers and tumor marker change in patients with advanced biliary tract cancer. MATERIALS AND METHODS: Patients with pathologically proven metastatic or relapsed biliary tract cancer who were treated in a phase II trial of first-line S-1 and cisplatin chemotherapy were enrolled. Serum tumor markers were measured at baseline and after the first cycle of chemotherapy. RESULTS: Among a total of 104 patients, 80 (77%) had elevated baseline tumor markers (69 with CA 19-9 elevation and 40 with CEA). A decline ≥ 30% of the elevated tumor marker level after the first cycle of chemotherapy conferred an improved time to progression (TTP), overall survival (OS), and better chemotherapy response. Multivariate analysis revealed tumor marker decline as an independent positive prognostic factor of TTP (adjusted hazard ratio [HR], 0.44; p=0.003) and OS (adjusted HR, 0.37; p < 0.001). Subgroup analysis revealed similar results in each group of patients with CA 19-9 elevation and CEA elevation. In addition, elevated baseline CEA was associated with poor survival in both univariate and multivariate analysis. CONCLUSION: Tumor marker decline was associated with improved survival in biliary tract cancer. Measuring tumor marker after the first cycle of chemotherapy can be used as an early assessment of treatment outcome.