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Purpose@#Heterogeneous human epidermal growth factor receptor 2 (HER2) overexpression in gastric cancer may lead to a misdiagnosis of HER2 status. Accurate assessment of HER2 status is essential for optimal treatment as novel HER2-directed agents are being investigated in various clinical settings. We evaluated the usefulness of HER2 re-assessment following progression on first-line treatment in initially HER2-negative advanced gastric cancer (AGC) patients. @*Materials and Methods@#We enrolled 177 patients with baseline HER2-negative AGC and performed HER2 re-assessment after progression on first-line treatment from February 2012 to June 2016 at Asan Medical Center, Seoul, Korea. The re-assessed HER2 status was analyzed with baseline HER2 status and clinical characteristics. @*Results@#The median age was 54 years (range, 24 to 80 years), and 123 patients (69.5%) were men. Seven patients (4.0%) were HER2-positive on the re-assessment. Patients with baseline HER2 negativity confirmed by a single test (n=100) had a higher HER2-positive re-assessment rate compared to those who had repeated baseline testing (n=77) (5.0% vs. 2.6%). Among the patients with single baseline HER2 testing, the rate was higher in patients with baseline HER2 immunohistochemistry (IHC) 1+ compared to those with IHC 0 (13.4% vs. 3.6%). @*Conclusion@#Overall, 4.0% of patients with baseline HER2-negative AGC were HER2-positive on re-assessment, and the HER2-positive re-assessment rate was higher among patients who had a single test at baseline. HER2 re assessment may be considered for initially HER2-negative patients to determine their eligibility for HER2-directed therapy, particularly if their HER2 negativity was determined by a single test, especially if they had a single baseline HER2 IHC 1+ test.
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Purpose@#This study aimed to report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors. @*Materials and Methods@#In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of maximum tolerated dose determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer. @*Results@#A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥ 3 adverse events were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The objective response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in two out of six patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%. @*Conclusion@#The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile (NCT01497704 and NCT02711969).
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Purpose@#This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns. @*Materials and Methods@#A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000–2003 (period 1), 2004–2007 (period 2), 2008–2011 (period 3), and 2012–2015 (period 4). @*Results@#There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The OS rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% CI, 15.5–20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8–11.6). @*Conclusion@#The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2–targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.
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Purpose@#This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns. @*Materials and Methods@#A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000–2003 (period 1), 2004–2007 (period 2), 2008–2011 (period 3), and 2012–2015 (period 4). @*Results@#There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The OS rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% CI, 15.5–20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8–11.6). @*Conclusion@#The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2–targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.
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OBJECTIVE: To evaluate the effectiveness, safety, and feasibility of intraoperative radiofrequency ablation (IORFA) under ultrasound guidance for the treatment of liver metastases from gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS: From August 2009 to February 2017, 24 patients with liver metastases of GISTs underwent IORFA, 14 underwent concurrent IORFA and primary GIST resection, and 10 underwent IORFA to treat hepatic recurrence after previous primary GIST resection. Seventy-six hepatic metastases were treated, of which 47 were surgically resected and 29 underwent IORFA. All included patients received imatinib therapy as standard treatment before and after IORFA or surgical resection. A retrospective medical record review was conducted, and follow-up data were collected. Technical success and effectiveness, overall and GIST-specific survival, and complications were assessed. RESULTS: The mean follow-up duration was 50.7 ± 34.7 months. The technical success rate of IORFA was 100%. New metastases developed in three of the 24 patients (12.5%) following a complete response 16, 51, and 95 months after IORFA, respectively. The cumulative one-, three-, and five-year overall survival rates were 100, 94.4, and 87.7%, respectively. The one-, three-, and five-year GIST-related survival rates were 100, 94.4, and 94.4%, respectively. Two major complications (biliary stricture and hepatic abscess) were observed. CONCLUSION: IORFA appears to be a feasible and safe treatment option for liver metastasis in patients with primary GISTs. In addition, IORFA and surgical resection may be complementary, helping to obtain complete response in cases of otherwise inoperable liver metastases secondary to GISTs.
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Humanos , Ablação por Cateter , Constrição Patológica , Seguimentos , Tumores do Estroma Gastrointestinal , Mesilato de Imatinib , Fígado , Prontuários Médicos , Metástase Neoplásica , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , UltrassonografiaRESUMO
PURPOSE: The purpose of this study was to evaluate the efficacy and safety of induction chemotherapy with docetaxel, capecitabine, and cisplatin (DXP) plus bevacizumab (BEV) on initially unresectable locally advanced gastric cancer (LAGC) or paraaortic lymph node (PAN) metastatic gastric cancer (GC). MATERIALS AND METHODS: Patients with LAGC or unresectable PAN metastatic GC received six induction chemotherapy cycles (60 mg/m2 docetaxel intravenously on day 1, 937.5 mg/m2 capecitabine orally twice daily on days 1-14, 60 mg/m2 cisplatin intravenously on day 1, and 7.5 mg/kg BEV intravenously on day 1 every 3 weeks), followed by conversion surgery. The primary endpoint was R0 resection rate. RESULTS: Thirty-one patients with invasion to adjacent organs but without PAN metastasis (n=14, LAGC group) or with PAN metastasis regardless of invasion (n=17, PAN group) were enrolled between July 2010 and December 2014. Twenty-seven patients (87.1%) completed six chemotherapy cycles. The most common grade ≥ 3 toxicities were neutropenia (71%), neutropenia with fever/infection (22.6%/3.2%), and stomatitis (16.1%). The clinical response and R0 resection rates were 64.3% (95% confidence interval [CI], 46.6 to 82.0) and 64.5% (LAGC group, 71.4%; PAN group, 58.8%), respectively. The pathological complete regression rate was 12.9%. After a median follow-up of 44.5 months (range, 39.4 to 49.7 months), the median progression-free survival and overall survival were 13.1 months (95% CI, 8.9 to 17.3) and 38.6 months (95% CI, 22.0 to 55.1), respectively. CONCLUSION: Induction chemotherapy with DXP+BEV displayed antitumor activities with encouraging R0 resection rate and manageable toxicity profiles on patients with LAGC or PAN metastatic GC.
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Humanos , Bevacizumab , Capecitabina , Cisplatino , Intervalo Livre de Doença , Tratamento Farmacológico , Seguimentos , Gastrectomia , Quimioterapia de Indução , Linfonodos , Metástase Neoplásica , Neutropenia , Neoplasias Gástricas , EstomatiteRESUMO
PURPOSE: The aim of this study was to confirm the efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors (GISTs) reported in the GRID phase III trial in Korean patients. MATERIALS AND METHODS: Fifty-seven Korean patientswith advanced GISTwho experienced both imatinib and sunitinib failure were enrolled in the management access program between December 2012 and November 2013 and treated with regorafenib (160 mg orally once daily in a 3 weeks on/1 week off). RESULTS: None of the patients achieved a complete or partial response while 25 patients (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 12.7 months (range, 0.2 to 27.6 months), the median progression-free survival and overall survival were 4.5 months (95% confidence interval [CI], 3.8 to 5.3) and 12.9 months (95% CI, 8.1 to 17.7), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of their cancer-related symptoms (abdominal pain in eight and abdominal distension in five) during the rest period for regorafenib, but all were ameliorated upon the resumption of regorafenib. The most common grade 3 or 4 adverse event was a hand-foot skin reaction (25%). The regorafenib dose was reduced in 44 patients (77%) due to toxicity, which manifested mainly as a hand-foot skin reaction (n=31). CONCLUSION: This study confirmed the efficacy and safety of regorafenib for advanced GIST after imatinib and sunitinib failure in Korean patients. Considering the exacerbation of the cancer-related symptoms observed during the rest periods, further exploration of the continuous dosing schedule of regorafenib is warranted in future clinical trials.
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Humanos , Agendamento de Consultas , Intervalo Livre de Doença , Seguimentos , Tumores do Estroma Gastrointestinal , Mesilato de Imatinib , PeleRESUMO
Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.
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Humanos , Inibidores da Angiogênese , Bevacizumab , Intervalo Livre de Doença , Junção Esofagogástrica , Oncologia , Metástase Neoplásica , Prognóstico , Estudos Prospectivos , Proteínas Tirosina Quinases , Neoplasias Gástricas , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
PURPOSE: The incidence of gastrointestinal stromal tumors (GISTs) harboring platelet-derived growth factor receptor alpha (PDGFRA) mutations is low, therefore further investigation of the efficacy of imatinib in this subgroup was needed. MATERIALS AND METHODS: Patients with PDGFRA-mutant GISTs who received imatinib as primary therapy for advanced disease between January 2000 and June 2012 were identified from the GIST registry of Asan Medical Center, Seoul, Korea. RESULTS: KIT and PDGFRA genotyping in 823 patients identified 18 patients (2%) with PDGFRA mutations who were treated with first-line imatinib. Exon 18 D842V substitution, non-D842V exon 18 mutations, and exon 12 mutations were detected in nine (50%), four (22%), and five (28%) patients, respectively. Objective response rate differed significantly between patients with the D842V mutation and those with non-D842V mutations (0% [0/5] vs. 71% [5/7], p=0.03). In all patients, median progression-free survival (PFS) and overall survival (OS) was 24.8 months (95% confidence interval [CI], 0.0 to 57.2) and 51.2 months (95% CI, 37.1 to 65.3), respectively. Significantly, poorer PFS was observed for patients with D842V-mutant GISTs than those with non-D842V PDGFRA-mutant GISTs: median 3.8 months (95% CI, 1.4 to 6.3) versus 29.5 months (95% CI, 18.3 to 40.7) (p < 0.001). Patients with the D842V mutation had poorer OS than those with non-D842V PDGFRA mutations: median 25.2 months (95% CI, 12.7 to 37.8) versus 59.8 months (95% CI, 43.0 to 76.5) (p=0.02). CONCLUSION: Imatinib is active against non-D842V PDGFRA-mutant GISTs, whereas GISTs harboring the D842V mutation are primarily resistant to imatinib.
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Humanos , Intervalo Livre de Doença , Éxons , Tumores do Estroma Gastrointestinal , Incidência , Coreia (Geográfico) , Fator de Crescimento Derivado de Plaquetas , Receptores do Fator de Crescimento Derivado de Plaquetas , SeulRESUMO
PURPOSE: Cancer clinical trials in Korea have rapidly progressed in terms of quantity and quality during the last decade. This study evaluates the current status of cancer clinical trials in Korea and their associated problems. MATERIALS AND METHODS: We analyzed the clinical trials approved by the Korea Food and Drug Administration (KFDA) between 2007 and 2013. A nationwide on-line survey containing 22 questions was also performed with several cooperative study groups and individual researchers in 56 academic hospitals. RESULTS: The number of cancer clinical trials approved by the KFDA increased almost twofold from 2007 to 2013. The number of sponsor-initiated clinical trials (SITs) increased by 50% and investigator-initiated clinical trials (IITs) increased by almost 640%. Three hundred and forty-four clinical trials were approved by the KFDA between 2012 and 2013. At the time of the on-line survey (August 2013), 646 SITs and 519 IITs were ongoing in all hospitals. Six high volume hospitals were each conducting more than 50 clinical trials, including both SITs and IITs. Fifty-six investigators (31%) complained of the difficulties in raising funds to conduct clinical trials. CONCLUSION: The number of cancer clinical trials in Korea rapidly increased from 2007 to 2013, as has the number of multicenter clinical trials and IITs run by cooperative study groups. Limited funding for IIT is a serious problem, and more financial support is needed both from government agencies and public donations from non-profit organizations.
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Humanos , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico , Administração Financeira , Apoio Financeiro , Órgãos Governamentais , Hospitais com Alto Volume de Atendimentos , Coreia (Geográfico) , Organizações sem Fins Lucrativos , Pesquisadores , United States Food and Drug AdministrationRESUMO
PURPOSE: This study evaluated the incidence of imatinib-associated skin rash, the interventional outcomes of severe rash, and impact of severe rash on the outcomes of imatinib treatment in gastrointestinal stromal tumor (GIST) patients. MATERIALS AND METHODS: A total of 620 patients were administered adjuvant or palliative imatinib for GIST at Asan Medical Center between January 2000 and July 2012. This analysis focused on a group of 42 patients who developed a severe rash requiring major interventions, defined as dose interruption or reduction of imatinib or systemic steroid use. RESULTS: Of the 620 patients treated with imatinib, 148 patients (23.9%) developed an imatinib-associated skin rash; 42 patients (6.8%) developed a severe rash requiring major intervention. Of these, 28 patients (66.8%) successfully continued imatinib with interventions. Serial blood eosinophil levels during imatinib treatment were associated with skin rash and severity. A significant association was observed between successful intervention and blood eosinophil level at the time of intervention initiation. In metastatic settings, patients with severe rash requiring major interventions tended to show poorer progression-free survival than patients who did not require major intervention and patients with no rash, although this finding was not statistically significant (p=0.326). CONCLUSION: By aggressive treatment of severe rash through modification of imatinib dose or use of systemic steroid, the majority of patients can continue on imatinib. In particular, imatinib dose intensity can be maintained with use of systemic steroid. Measuring the blood eosinophil levels may be helpful in guiding the management plan for skin rash regarding the intensity and duration of interventions.
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Humanos , Intervalo Livre de Doença , Eosinófilos , Exantema , Tumores do Estroma Gastrointestinal , Incidência , Pele , Resultado do TratamentoRESUMO
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries.
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Humanos , Povo Asiático , China , Consenso , Diagnóstico , Tumores do Estroma Gastrointestinal , Trato Gastrointestinal , Mesilato de Imatinib , Coreia (Geográfico) , OncologiaRESUMO
Although surgical resection remains the only curative treatment for gastric cancer, locoregional and distant recurrence are still common after surgical resection with curative intent underscoring the importance of a multimodal approach. In recent decades, there have been notable improvements in multidisciplinary treatments for gastric cancer that influence clinical decision and treatment algorithms; these include surgery, chemotherapy, and radiotherapy. Notably, multimodal and multidisciplinary approaches to gastric cancer have developed in various ways according to geographical regions in the context of variations in disease incidence, etiology/epidemiology, clinical features, and treatment outcome. Differences in surgical techniques, curative resection rate, survival outcomes after curative resection, and relapse patterns between the East and West lead to different perioperative multidisciplinary strategies. In Western countries, low rates of curative resection and high rates of locoregional recurrence following suboptimal surgery, in addition to systemic spread after surgery, provide a rationale for perioperative chemotherapy (preoperative and postoperative chemotherapy) and postoperative chemoradiation. In contrast, Eastern countries have focused on reducing systemic failures by emphasizing postoperative chemotherapy after curative resection. To further improve perioperative treatment in localized gastric cancer, more sophisticated risk stratification and novel therapeutic strategies such as molecularly targeted agents need to be investigated, based on an understanding of the molecular pathogenesis of the disease.
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Quimiorradioterapia , Tratamento Farmacológico , Incidência , Radioterapia , Recidiva , Neoplasias Gástricas , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Although surgical resection remains the only curative treatment for gastric cancer, locoregional and distant recurrence are still common after surgical resection with curative intent underscoring the importance of a multimodal approach. In recent decades, there have been notable improvements in multidisciplinary treatments for gastric cancer that influence clinical decision and treatment algorithms; these include surgery, chemotherapy, and radiotherapy. Notably, multimodal and multidisciplinary approaches to gastric cancer have developed in various ways according to geographical regions in the context of variations in disease incidence, etiology/epidemiology, clinical features, and treatment outcome. Differences in surgical techniques, curative resection rate, survival outcomes after curative resection, and relapse patterns between the East and West lead to different perioperative multidisciplinary strategies. In Western countries, low rates of curative resection and high rates of locoregional recurrence following suboptimal surgery, in addition to systemic spread after surgery, provide a rationale for perioperative chemotherapy (preoperative and postoperative chemotherapy) and postoperative chemoradiation. In contrast, Eastern countries have focused on reducing systemic failures by emphasizing postoperative chemotherapy after curative resection. To further improve perioperative treatment in localized gastric cancer, more sophisticated risk stratification and novel therapeutic strategies such as molecularly targeted agents need to be investigated, based on an understanding of the molecular pathogenesis of the disease.
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Quimiorradioterapia , Tratamento Farmacológico , Incidência , Radioterapia , Recidiva , Neoplasias Gástricas , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Vasoactive intestinal polypeptide-secreting tumors (VIPomas) cause VIPoma syndrome, which is characterized by watery diarrhea, hypokalemia, and achlorhydria. The treatment options for metastatic VIPomas include somatostatin analogs, cytoreductive surgery, and chemotherapy. We report the case of a 54-year-old male who presented with a peripancreatic mass with multiple hepatic metastases on computed tomography. After resection, the peripancreatic mass was demonstrated pathologically to be a neuroendocrine tumor. Although the patient received systemic chemotherapy and somatostatin analogs for the hepatic metastatic masses, the tumor increased in size. The patient then experienced severe diarrhea, despite treatment with the somatostatin analogs. Elevated serum VIP levels (3,260 pg/mL) and typical symptoms confirmed the diagnosis of VIPoma. We performed hepatic artery embolization (HAE) to reduce the tumor volume and control his symptoms, which led to a very rapid symptomatic response. The patient has remained symptom-free for 18 months with repeated HAE.
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Humanos , Masculino , Pessoa de Meia-Idade , Acloridria , Diagnóstico , Diarreia , Tratamento Farmacológico , Artéria Hepática , Hipopotassemia , Fígado , Metástase Neoplásica , Tumores Neuroendócrinos , Somatostatina , Carga Tumoral , VipomaRESUMO
Gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the gastrointestinal tract, have represented an important advance in oncology field with the success of molecular targeted therapy. Since the approval of the tyrosine kinase inhibitor (imatinib) in 2002, the survival of patients with advanced GISTs has significantly increased. Accurate histopathologic diagnosis of GISTs and multidisciplinary approach has become more important for successful management of GISTs. Recently, imatinib has become a standard treatment even in adjuvant setting, and regorafenib has been approved for advanced GIST after failure of imatinib and sunitinib. This review presents here the updated results of relevant clinical studies for the further revision to the guideline of Korean GIST study group. We hope this review will help enhance the quality of diagnosis, treatment, and care of patients with GIST in Korea.
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Humanos , Benzamidas , Tumores do Estroma Gastrointestinal , Trato Gastrointestinal , Indóis , Coreia (Geográfico) , Terapia de Alvo Molecular , Compostos de Fenilureia , Piperazinas , Proteínas Tirosina Quinases , Piridinas , Pirimidinas , Pirróis , Mesilato de ImatinibRESUMO
Gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the gastrointestinal tract, have represented an important advance in oncology field with the success of molecular targeted therapy. Since the approval of the tyrosine kinase inhibitor (imatinib) in 2002, the survival of patients with advanced GISTs has significantly increased. Accurate histopathologic diagnosis of GISTs and multidisciplinary approach has become more important for successful management of GISTs. Recently, imatinib has become a standard treatment even in adjuvant setting, and regorafenib has been approved for advanced GIST after failure of imatinib and sunitinib. This review presents here the updated results of relevant clinical studies for the further revision to the guideline of Korean GIST study group. We hope this review will help enhance the quality of diagnosis, treatment, and care of patients with GIST in Korea.
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Humanos , Benzamidas , Tumores do Estroma Gastrointestinal , Trato Gastrointestinal , Indóis , Coreia (Geográfico) , Terapia de Alvo Molecular , Compostos de Fenilureia , Piperazinas , Proteínas Tirosina Quinases , Piridinas , Pirimidinas , Pirróis , Mesilato de ImatinibRESUMO
Imatinib, the first-line treatment in patients with advanced gastrointestinal stromal tumors (GIST), is generally well tolerated, although some patients have difficulty tolerating the standard dose of 400 mg/day. Adjusting imatinib dosage by plasma level monitoring may facilitate management of patients who experience intolerable toxicities due to overexposure to the drug. We present two cases of advanced GIST patients in whom we managed imatinib-related toxicities through dose modifications guided by imatinib plasma level monitoring. Imatinib blood level testing may be a promising approach for fine-tuning imatinib dosage for better tolerability and optimal clinical outcomes in patients with advanced GIST.
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Idoso , Humanos , Masculino , Antineoplásicos/sangue , Benzamidas/sangue , Monitoramento de Medicamentos , Éxons , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Neoplasias Hepáticas/secundário , Mutação , Piperazinas/sangue , Tomografia por Emissão de Pósitrons , Proteínas Proto-Oncogênicas c-kit/genética , Pirimidinas/sangue , Tomografia Computadorizada por Raios XRESUMO
Despite their rarity in incidence and prevalence, gastrointestinal stromal tumors (GISTs) have emerged as a distinct and noteworthy pathogenetic entity. The clinical management of GISTs has rapidly evolved due to the recent elucidation of their oncogenic signal transduction pathway and the introduction of molecular-targeted therapies. Successful management of GISTs requires a multidisciplinary approach firmly based on an accurate histopathologic diagnosis. In 2007, the Korean GIST study group published the first guideline for optimal diagnosis and treatment of GISTs in Korea. The second version of the guideline was published in 2010. Herein, we provide the results of relevant clinical studies for the purpose of further revision to the guideline. We expect this new guideline will enhance the accuracy of diagnosis, as performed by members of the Korean associate of physicians involved in GIST patient care, thus improving the efficacy of treatment.
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Benzamidas , Tumores do Estroma Gastrointestinal , Incidência , Indóis , Coreia (Geográfico) , Terapia de Alvo Molecular , Assistência ao Paciente , Piperazinas , Prevalência , Pirimidinas , Pirróis , Transdução de Sinais , Mesilato de ImatinibRESUMO
BACKGROUND: The purpose of the present study was to investigate the clinico-hematological findings of bone marrow (BM) involvement and leukemic phase in Korean patients with non-Hodgkin lymphoma (NHL). METHODS: We included 791 patients with NHL that were classified with the WHO (2008) criteria. Laboratory data, bone marrow histomorphologic features and medical records were reviewed. Leukemic phase was defined as when the proportion of neoplastic lymphoid cells comprised more than 10% of leukocytes in the peripheral blood or more than 25% of nucleated cells in the BM. RESULTS: We found that 21.7% (172/791) of the patients had BM involvement, and 6.2% (49/791) developed leukemic phase of the disease. NHL subtypes showing high frequencies of leukemic phase development were mantle cell lymphoma (40%), angioimmunoblastic T cell lymphoma (40%), lymphoblastic lymphoma (36.4%), and Burkitt lymphoma (26.1%). Compared to B-cell type, T-cell type of NHL showed significantly higher frequencies of BM involvement (18.6% vs 30.9%; P=0.0004) and leukemic phase development (4.8% vs 10.3%, P=0.008). Complete remission rate was significantly lower in leukemic (55.6%) than in non-leukemic (85.9%) group of patients (P=0.0002), whereas relapse rate was not different between the two groups. Death rate was higher in leukemic (46.9%) than in non-leukemic (30.1%) group of patients, and the 5-yr overall survival probability was significantly lower in leukemic group (P=0.02). CONCLUSIONS: The incidence of leukemic phase development in NHL was lower in Korean patients than that reported for Western populations and higher in T-cell lymphoma. We confirmed that the presence of leukemic phase in NHL patients is associated with a poor prognosis.