Chinese expert consensus on the clinical application of the Chinese modified triplet combination with irinotecan, oxaliplatin and continuous infusional 5-fluorouracil/leucovorin for colorectal cancer / 中华胃肠外科杂志

Colorectal cancer is the second most common malignant tumor in China. The FOLFOXIRI regimen, which combines 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan, is a high-intensity and highly effective chemotherapy regimen. However, the original regimen is poorly tolerated in Chinese patients. In order to promote the standardized and rational application of FOLFOXIRI regimen by clinicians in China, "

Huge recurrent gastric neuroendocrine tumor: a second-line chemotherapeutic dilemma

Chemotherapy is considered "state of the art" for the treatment of poorly differentiated neuroendocrine neoplasms. Unfortunately, there is no standard effective post-first-line treatment for relapsing high-grade gastroenteropancreatic neuroendocrine neoplasms. We report the case of a patient with a gastric neuroendocrine carcinoma stage IV, with massive gastrointestinal bleeding at diagnosis. After the first line of platin-based chemotherapy a major tumoral response was documented, but the patient relapsed after 4 months. A second line of chemotherapy treatment was given, with the FOLFOX regimen, and the patient has been free of progression for almost 2 years. There is no second-line standard treatment accepted for this type of carcinoma, but 5-fluorouracil combined with oxaliplatin showed interesting antitumor activity.

Primary Adenocarcinoma with Focal Choriocarcinomatous Differentiation in the Sigmoid Colon / 대한소화기학회지

Primary colorectal choriocarcinoma is a rare neoplasm. Only 19 cases have been reported worldwide, most of which involved adenocarcinomas. The prognosis is usually poor, and the standard therapy for this tumor has not been established. A 61-year-old woman presented with constipation and lower abdominal discomfort. She was diagnosed with primary adenocarcinoma with focal choriocarcinomatous differentiation in the sigmoid colon and liver metastasis. Because the serum beta-human chorionic gonadotropin level was not significantly elevated, and because only focal choriocarcinomatous differentiation was diagnosed, we selected the chemotherapy regimen that is used for the treatment of metastatic colorectal adenocarcinoma. The patient survived for 13 months after the initial diagnosis. This is the first case in Korea to assess the suppressive effects of the standard chemotherapy for colorectal adenocarcinoma against coexisting colorectal choriocarcinoma and adenocarcinoma.

Efficacy and Safety of FOLFIRI as Second-line Chemotherapy in Advanced Gastric Cancer / 대한소화기학회지

No abstract available.

Compostos coordenados híbridos de platina no tratamento do câncer / Platinum hybrid coordinated compounds in cancertreatment

O câncer, ou neoplasia, é uma doença caracterizada pela propagação descontrolada de formas anormais das próprias células corporais e corresponde à segunda doença que mais causa mortes no mundo. A história da platina no tratamento do câncer teve início com a descoberta da sua atividade, em 1965, com a aprovação para uso clínico acontecendo apenas após 10 anos. Atualmente, os fármacos com platina estão entre os mais bem sucedidos agentes anticancerígenos, onde se destacam cisplatina (1), carboplatina (2) e oxaliplatina (3). Seus mecanismos de ação são similares: estes fármacos formam adutos com o DNA, impedindo a sua síntese e reparo, levando à morte celular. Contudo, os efeitos adversos desencadeados pelo tratamento e o desenvolvimento de resistência ao medicamento têm limitado suas aplicações. Uma das principais estratégias para a diminuição de tais efeitos consiste em alterar a estrutura destas moléculas, levando à formação de compostos híbridos, que se caracterizam pela presença de pelo menos dois fragmentos funcionais distintos em uma mesma molécula e podem apresentar maior espectro de atividade antitumoral. Dentre as alterações mais comuns encontram-se a modificação da solubilidade, através da inserção de grupos abandonadores mais ou menos hidrofóbicos e a introdução de ligantes com atividade biológica própria. Dessa forma, esta revisão visa verificar os avanços mais recentes na síntese de compostos híbridos de platina, bem como as melhorias na atividade anticâncer dos novos compostos platinados...

Cancer, or neoplasm, is a disease characterized by the uncontrolled propagation of abnormal cells of the body and is the second leading death-causing disease. The history of platinum in cancer treatment goes back to the discovery of its activity in 1965 and its approval for clinical use just 10 years later. Some of the most successful anticancer agents are Pt-based chemotherapeutics, among which cisplatin (1), carboplatin (2), and oxaliplatin (3) stand out. They have similar mechanisms of action: they form adducts with DNA, preventing its synthesis and repair and leading to cell death. However, adverse effects triggered by treatment and the development of resistance to these drugs have limited their application. One of the most important strategies to reduce such effects is to carry out structural modifications of these molecules, leading to hybrid compounds that are characterized by the presence of at least two distinct functional fragments on the same molecule and can exhibit a broader antitumor activity spectrum. Among the most typical modifications are changes to the solubility pattern, created by the insertion of leaving groups with high or low hydrophobicity, and the introduction of biologically active ligands as non-leaving groups. The purpose of these strategies is to obtain compounds capable of reducing systemic toxicity and/or overcoming acquired resistance factors to cisplatin. Therefore, the aim of this review is to discuss the most recent advances in the synthesis of hybrid platinum compounds, as well as improvements in the anticancer activity of Pt-compounds...

Use of microRNAs in directing therapy and evaluating treatment response in colorectal cancer / Utilização dos microRNAs no direcionamento da terapia e na avaliação da resposta ao tratamento do câncer colorretal

Colorectal cancer is the third most common cancer worldwide. Survival and prognosis depend on tumor stage upon diagnosis, and in more than 50% of cases, the tumor has already invaded adjacent tissues or metastasis has occurred. Aiming to improve diagnosis, clinical prognosis and treatment of patients with colorectal cancer, several studies have investigated microRNAs as molecular markers of the disease due to their potential regulatory functions on tumor suppressor genes and oncogenes. This review aimed to summarize the main topics related to the use of microRNAs in diagnosis, clinical prognosis and evaluating treatment response in colorectal cancer.

O câncer colorretal é o terceiro tipo de câncer mais comum em todo o mundo. A sobrevivência e o prognóstico dependem do estágio do tumor no diagnóstico, momento em que, em mais de 50% dos casos, o tumor já invadiu tecidos adjacentes ou ocorreu metástase. Objetivando-se melhorar o diagnóstico, o prognóstico clínico e o tratamento de pacientes com câncer colorretal, vários estudos investigaram microRNAs como marcadores moleculares da doença, devido à sua função reguladora potencial sobre genes supressores de tumor e oncogenes. Esta revisão procura resumir os principais tópicos relacionados ao uso de microRNAs no diagnóstico, na determinação do prognóstico clínico e na avaliação de resposta ao tratamento do câncer colorretal.

Prognostic impact of epithelial cell adhesion molecule in ovarian cancer patients / 부인종양

No abstract available.

Prognostic Factors for Metastatic Colorectal Cancer after First-line Chemotherapy with FOLFOX-4 or FOLFIRI Regimen / 대한소화기학회지

BACKGROUND/AIMS: Information on prognostic factors for metastatic colorectal cancer is an important basis for planning the treatment and predicting the outcomes of the patients; however, it has not been well established. The aim of this study was to identify factors that predict results of chemotherapy and to establish a plan for treatment of patients whose tumors are inoperable due to metastatic colorectal cancer. METHODS: We conducted a retrospective review of records from 75 patients treated for colorectal cancer in Kosin University Gospel Hospital, from October 2004 to September 2008. Patients with inoperable tumors due to metastasis at the time of diagnosis who were treated with oxaliplatin or irinotecan as the first-line treatment were included in this study. We investigated the factors that might have an effect on overall survival. RESULTS: A total of 75 patients were included in this study. Results of univariate analysis showed that hemoglobin (Hb) > or =10 g/dL at the time of diagnosis, no increase in CEA on the follow-up examination after chemotherapy, chemotherapy plus surgery, and better response to chemotherapy were significant prognostic factors. Results of multivariate analysis showed that Hb > or =10 g/dL at the time of diagnosis (p or =10 g/dL at the time of diagnosis, surgery after chemotherapy, and better response to chemotherapy were significant prognostic factors for metastatic colorectal cancer.

Overexpression of the epithelial cell adhesion molecule is associated with a more favorable prognosis and response to platinum-based chemotherapy in ovarian cancer / 부인종양

OBJECTIVE: Epithelial cell adhesion molecule (EpCAM) has experienced a renaissance lately as a binding site for targeted therapy as well as a prognostic marker in epithelial malignancies. Aim of this study was to study EpCAM as a potential prognostic marker in epithelial ovarian cancer (EOC). METHODS: EpCAM expression was assessed by immunohistochemistry on paraffin-embedded primary EOC-tissue samples. EpCAM overexpression was defined as an expression of EpCAM of 76% to 100%. Tissue samples and clinical data were systematically collected within the international and multicenter "Tumorbank Ovarian Cancer" network. RESULTS: Seventy-four patients, diagnosed with EOC between 1994 and 2009, were included in the study (median age, 56 years; range, 31 to 86 years). The majority of the patients (81.1%) presented with an advanced stage International Federation of Gynecology and Obstetrics (FIGO) III/IV disease. Histology was of the serous type in 41 patients (55.4%), endometrioid in 19 (25.6%), and mucinous in 14 (19%). EpCAM was overexpressed in 87.7%. Serous tumors overexpressed EpCAM significantly more often than mucinous tumors (87.8% vs. 78.6%, p=0.045); while no significant difference was noted between the other histological subgroups. EpCAM overexpression was significantly associated with a better progression free survival and higher response rates to platinum based chemotherapy (p=0.040 and p=0.048, respectively). EpCAM was identified as an independent prognostic marker for overall survival (p=0.022). CONCLUSION: Our data indicate a significant association of EpCAM overexpression with a more favorable survival in EOC-patients. Serous cancers showed a significant EpCAM overexpression compared to mucinous types. Larger multicenter analyses are warranted to confirm these findings.

Usefulness of Carcinoembryonic Antigen for Monitoring Tumor Progression during Palliative Chemotherapy in Metastatic Colorectal Cancer

PURPOSE: To evaluate the efficacy of carcinoembryonic antigen (CEA) measurement for monitoring tumor progression during palliative chemotherapy in metastatic colorectal cancer. MATERIALS AND METHODS: Forty-eight patients with initially unresectable metastatic colorectal cancer (n=26, 54.2%) or recurrent unresectable metastatic colorectal cancer (n=22, 45.8%) received FOLFOX-4 chemotherapy for palliation. Serum CEA levels and carbohydrate antigen 19-9 levels were measured and computed tomography (CT) studies were performed prior to chemotherapy and after 3 cycles of chemotherapy. From the CT images, tumor responses were evaluated according to the Response Evaluation Criteria in Solid Tumors criteria and categorized as complete response, partial response, stable disease, and progressive disease. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of tumor marker assessments for determining tumor response were calculated. RESULTS: The sensitivity, specificity and diagnostic accuracy of CEA assessment for prediction of disease progression were 50%, 77% and 69%, respectively. When the patients were dichotomized according to baseline CEA level, the initially elevated CEA group showed higher sensitivity and higher diagnostic accuracy compared to the initially normal CEA group (sensitivity=67% vs. 20%; diagnostic accuracy=71% vs. 62%). CONCLUSION: CEA assessment could be useful for monitoring tumor progression during palliative chemotherapy in only patients with initially elevated CEA level.

FOLFOX (oxaliplatin and 5fluorouracil/leucovorin) in patients with untreated metastatic gastric adenocarcinoma Phase II study.

Background: Oxaliplatin has shown promising activity in metastatic gastric cancer (MGC) and has synergism with 5 fluorouracil. This phase II study was performed to evaluate the efficacy and safety of FOLFOX4 regimen in MGC. Materials and Methods: Patients with MGC, aged 18-70 years, performance status ≤2, no prior chemotherapy, received FOLFOX4 regimen every 2 weeks as oxaliplatin 85 mg/m 2 IV infusion on day 1 and leucovorin 200 mg/m 2 IV infusion followed by fluorouracil 400 mg/m 2 IV bolus and 600 mg/m 2 22-hour continuous infusion on days 1 and 2. Treatment was administered until progression, unacceptable toxicity, patient's refusal or for a maximum of 12 cycles. Results: From August 2007 to June 2010, 34 patients were prospectively enrolled. The median age was 52 years (28-69). In total, 293 cycles were administered with a median of 8 cycles per patient (range 1-12 cycles) and 33 of 34 patients were assessable for treatment response. The overall response rate were 53% with one patient(3%) had complete response, 17 patients (50%) had partial responses and 6 patients (18%) had stable disease. The median survival of all patients was 12.1 months and the median time to progression was 9.4 months. The most common grade 3/4 toxic effects were neutropenia in four patients (12%), diarrhea in three patients (9%), vomiting in two patients (6%) and peripheral neuropathy occurred in three patients (9%). Conclusions: The FOLFOX4 combination chemotherapy showed a very promising antitumor activity and was generally well-tolerated as a first-line treatment of patients with MGC.

Comparison of the Toxicities and Efficacies of the Combination Chemotherapy Regimens in Advanced Gastric Cancer Patients Who Achieved Complete Response after Chemotherapy / 대한소화기학회지

BACKGROUND/AIMS: We retrospectively analyzed comparative toxicities and efficacies of chemotherapy regimens in advanced gastric cancer (AGC) patients who achieved complete response (CR) after chemotherapy. METHODS: We reviewed the medical records of 1,203 patients, who were pathologically diagnosed as AGC in a single center between January 2001 and October 2007. On the basis of the Response Evaluation Criteria in Solid Tumors, CR was evaluated with abdominal computed tomography. Toxicities were evaluated using the National Cancer Institute's common toxicity criteria before each chemotherapy cycle. RESULTS: Among the 1,203 AGC patients enrolled in this study, 568 received chemotherapy and 635 received best supportive care. The major chemotherapy regimens were 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), docetaxel, cisplatin and 5-fluorouracil (DCF) and 5-fluorouracil, leucovorin and irinotecan (FOLFIRI). Among the 568 patients, 51 (9.0%) achieved CR (49 [8.6%] with FOLFOX [n=12], DCF [n=26], or FOLFIRI [n=11] and 2 [0.3%] with etoposide, leucovorin and 5-fluorouracil). For patients administered FOLFOX, DCF, and FOLFIRI, the median time to disease progression was 4 months (range, 1.8-59.5), 15 months (range, 2.9-31.2) and 10 months (range, 2.0-39.5), and the median survival times were 48 months (range, 5.9-74.0), 37 months (range, 14.0-86.0), and 30 months (range, 6.0-50.0), respectively. Grades 3-4 mucositis occurred mostly in patients administered DCF (n=8, 30.8%). Grades 3-4 leucopenia were observed in 1 (8.3%), 11 (42.3%), and 4 (36.4%) patients administered FOLFOX, DCF and FOLFIRI, respectively. No statistically significant differences were observed in the 3 regimens. CONCLUSIONS: All 3 regimens (FOLFOX, DCF and FOLFIRI) were active and tolerable. Their efficacies and toxicities were not significantly different.

Second Line Chemotherapy for Pancreatic Cancer / 대한소화기학회지

Pancreatic cancer is a very lethal cancer. It is the 5th most common cause for cancer related mortality in Korea. Most of patients have unresectable pancreatic cancer, and systemic chemotherapy remains the only treatment option for them. Gemcitabine has been adopted as the standard first-line agent for advanced pancreatic cancer, but the progression free survival with gemcitabine is short. Many of patients need further treatment. We reviewed the clinical trials of second line chemotherapy for gemcitabine refractory pancreatic cancer and tried to show currently available treatment options.

Oxaliplatin and Leucovorin Plus Fluorouracil Versus Irinotecan and Leucovorin Plus Fluorouracil Combination Chemotherapy as a First-line Treatment in Patients with Metastatic or Recurred Gastric Adenocarcinoma / 대한소화기학회지

BACKGROUND/AIMS: We performed retrospective study in order to compare oxaliplatin, leucovorin, and fluorouracil (FOLFOX) versus irinotecan, leucovorin, and fluorouracil (FOLFIRI) in recurred or metastatic gastric adenocarcinoma. METHODS: We investigated 56 patients who were diagnosed with recurred or metastatic gastric adenocarcinoma in a single center during march, 2003 to march, 2008. The patients received either FOLFOX or FOLFIRI chemotherapy. RESULTS: There were no significant difference between the Oxaliplatin group (30 patients) and Irinotecan group (26 patients) in sex, age, and ECOG performance (p>0.05). Oxaliplatin group showed 1 case of CR (3.3%) and 12 cases of PR (40%), making the response rate 43.3%. Irinotecan group showed CR in 2 cases (7.7%) and PR in 10 cases (38.5%), making the response rate 46.2%. The median value of time to progression was 4 months in the oxlaplatin group and 4.5 months in the irinotecan group. The overall survival showed no significant difference (p=0.784), with the irinotecan group (9.7 months) being slightly longer than the Oxaliplatin group (8.3 months). Grade 3/4 neutropenia occurred similarly in both groups (4 cases in the oxalplatin group, 9 in the irinotecan group). CONCLUSIONS: Both combination treatment can be used safely and effectively in recurred or metastatic gastric adenocarcinoma.

Carcinoma de células acinares del páncreas: reporte de un caso / Acinar cell carcinoma of the pancreas: case report

Objetivo: Reportar el caso de una paciente con carcinoma de células acinares de páncreas como una entidad clinico-patológica infrecuente. Método: Presentación del caso clínico y revisión de la literatura. Ambiente: Servicio de Cirugía General del Hospital Universitario de Los Andes. Mérida. Estado Mérida. Venezuela. Resultados: Paciente femenino de 21 años de edad, que refiere enfermedad actual de 12 meses de evolución, caracterizada por aumento de volumen en epigastrio e hipocondrio izquierdo y sensación de plenitud postprandial. Por estudios imagenológicos se evidencia tumoración en cuerpo y cola pancreática. Se realiza laparotomía subcostal bilateral, encontrando tumoración de 20 x 15 x 10 cm en cuerpo y cola pancreática, encapsulada, con áreas sólidas y quísticas, no adherida a órganos vecinos y de 850 gr de peso; se realizó pancreatectomía corporocaudal, sin preservación esplénica. El reporte histopatológico fue carcinoma acinar de páncreas. Actualmente sin complicaciones de la función endocrina y sin evidencias de recidiva. Discusión: El carcinoma de células acinares es una entidad poco frecuente que representa del 1 al 2 por ciento de los tumores pancreáticos exocrinos. Ocurre con mayor frecuencia en hombres de edad media o mayores. Clínicamente cursan con dolor difuso y aumento del volumen abdominal. Por lo general afectan al cuerpo y cola del páncreas, son tumores encapsulados, de gran tamaño, que presentan distintos patrones de crecimiento. La supervivencia es variable, entre 1 y 3 años, dependiendo de la presencia o no de metástasis.

We report a 21 years old female presenting with a history of 12 months of a lump located in the epigastrium. An abdominal CAT scan showed a tumor located in the pancreatic body and tail. The patient was operated, and during the laparotomy an encapsulated tumor of the pancreas measuring 20 x 15 x 10 cm was found. The body and tail of the pancreas were excised and the pathological study of the surgical piece disclosed an acinar cell carcinoma. In the postoperative period the patient received chemotherapy with gemcitabine and oxaliplatin. After three years of follow up, she is in good conditions and without evidences of tumor relapse.

Chemotherapy for Colorectal Cancer / 대한소화기학회지

Recent advances in chemotherapy lead to improved survival outcomes in patients with colorectal cancer. The 5-fluorouracil (5-FU) is still one of the important chemotherapeutic agents since 1950s, but the introduction of newer cytotoxic agents, irinotecan and oxaliplatin, or targeted agents, bevacizumab and cetuximab, have changed treatment strategies for these patients. A deliberate choice should be made for adjuvant chemotherapy, because it has became complicated more than ever before. Oxaliplatin plus 5-FU seemed to be superior in terms of disease-free and overall survival than 5-FU alone after curative surgery for colon cancers. However not all of these patients seemed to receive benefit from this intensive adjuvant treatment, and some limitations are present according to the postoperative stage, tumor biology and clinical characteristics. For metastatic disease, there is no doubt that more complicated strategies are present because we have more abundant chemotherapeutic agents available for metastatic setting compared to adjuvant setting. Recently, targeted agents, such as bevacizumab or cetuximab, also took an important place in the treatment of metastatic colorectal cancer, and many efforts are also made to find the biomarkers for predicting treatment responses to these targeted agents. In this review, we intended to sort up the standard strategies of chemotherapy for patients with colorectal cancer according to the latest pivotal publications.

Is there a positive effect of participation on a clinical trial for patients with advanced non-small cell lung cancer?

BACKGROUND: There is general belief that patients who enrolled on a clinical trial have better outcomes compared to those who are treated outside of a trial. We analyzed if there was a 'trial effect' for patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy. MATERIALS AND METHODS: A retrospective analysis of cohorts of patients with advanced NSCLC who received chemotherapy inside and outside of a clinical trial were analyzed for response rates (RR), progression free survival (PFS), overall survival (OS), 1 and 2 year survival. RESULTS: There were 194 patients who received chemotherapy of which, 54 were on a clinical trial and 140 outside of it. For the whole group, the RR, median PFS, OS, one and two-year survivals were 35.4%, six months (range, 2-70), seven months (range, 2-72), 29.8% and 9.7% respectively. The differences in RR and PFS of patients who were treated inside and outside of a clinical trial were not significant (P=0.6164, 0.0881). The differences in median OS and one-year survivals between the groups were significant (P=0.0052, 0.022). For the whole group, patients who received II line chemotherapy had better OS (P< or = 0.0001). More patients in the trial group received II line chemotherapy (P=0.0004).The difference in the median OS between the groups continued to be significant even after patients who received II line chemotherapy were censored (P=0.0437). CONCLUSION: Patients with advanced NSCLC who were treated inside of a clinical trial had better OS compared to those who were treated outside of it.

Capecitabine and Oxaliplatin (XELOX) for the Treatment of Patients with Metastatic Gastric Cancer and Severe Liver Dysfunction

Gastric cancer patients with severe liver dysfunction secondary to hepatic metastases have limited treatment options. Most cytotoxic drugs have a narrow therapeutic index. Although both capecitabine and oxaliplatin have been well tolerated as single agents for patients with severe hepatic dysfunction, the combination of these drugs has not been investigated. We report here on a case of successful treatment of a patient suffering with severe liver dysfunction and metastatic gastric cancer; the patient was treated with a combination of capecitabine and oxaliplatin (XELOX). The initial bilirubin level of the patient was 10.9 mg/dL. After two cycles of treatment, his bilirubin level decreased to 2.1 mg/dL. He has experienced an excellent radiological response and he has received six cycles of XELOX chemotherapy. XELOX chemotherapy is feasible and it can be associated with positive outcomes for the patients suffering with metastatic gastric cancer and severe liver dysfunction.

Irinotecan and oxaliplatin: an overview of the novel chemotherapeutic options for the treatment of advanced colorectal cancer

Colorectal cancer is one of the most frequent malignancies in humans and an important cause of cancer death. Metastatic colorectal cancer remains incurable with available systemic therapeutic options. The most active cytotoxic drug against this malignancy, the antimetabolite 5-fluorouracil, was developed more than forty years ago, and as a single agent produces responses in only 10 to 15 percent of patients which in general last less than one year. Efforts to ameliorate these poor results resulted in the 5-fluorouracil/leucovorin combination, which enhances response rates about two-fold, without, however, significantly improving survival rates. The recent emergence of a handful of new 5-fluorouracil analogues and folate antagonists, as well as the topoisomerase I inhibitor irinotecan, and the third-generation platinum compound oxaliplatin, is likely to alter this gloomy scenario. These agents are at least as effective as 5-fluorouracil in patients with advanced colorectal carcinoma, both untreated and previously treated with 5-fluorouracil-based regimens. This has led to the approval of irinotecan as second-line treatment for 5-fluorouracil-refractory disease, while the use of oxaliplatin has been suggested for patients having a defective 5-fluorouracil catabolism. Recently, FDA approved the combination of irinotecan with 5-fluorouracil and leucovorin for first-line treatment of advanced colon cancer. Based on the synergistic preclinical antitumor effects of some of these agents, their meaningful single-agent activity, distinct mechanisms of cytotoxicity and resistance, and only partially overlapping toxicity profiles, effective combination regimens are now being developed, which are likely to lead to a new, more hopeful era for patients suffering from advanced colorectal carcinoma