Effect of FOLFOX6 chemotherapy on serum VEGF expression in advanced colorectal cancer patients

SUMMARY OBJECTIVE: To explore the effect of FOLFOX6 chemotherapy on serum vascular endothelial growth factor (VEGF) expression in advanced colorectal cancer patients. METHODS: A retrospective analysis of 81 patients with advanced colorectal cancer who visited our hospital from March 2014 to February 2016 was performed. All the patients were treated with FOLFOX6 chemotherapy. On day 1, patients received oxaliplatin 100 mg/m2 ivgtt (2h), calcium folinate 200 mg/m2 ivgtt (2h), 5 fluorouracil 400 mg/m2 iv bolus and 5 fluorouracil 2500 mg/m2 ivgtt (5h). The treatment course was 2 weeks, and 4 treatment courses were required. The changes in the levels of VEGF and CRP and quality of life before and after 4 courses of chemotherapy were observed and therapeutic effects and adverse reactions after chemotherapy were evaluated. RESULTS: After treatment, the total efficiency of chemotherapy was 82.72% (67/81) with 24 cases in complete remission, 25 cases in partial response, 18 cases in stable disease and 14 cases in progressive disease. The levels of CRP and VEGF after the treatment were significantly lower than those before treatment (5.69±0.77) mg/L vs. (7.99±1.36) mg/L; (443.26±21.55) pg/mL vs. (542.83±20.44) pg/mL] (P<0.05). The KPS grade after treatment was significantly higher than that before treatment (57.84±4.6) point vs. (50.99±3.73) point] (P<0.05). Among them, 3 cases developed a rash, 5 cases experienced hair loss, and 9 cases developed nausea and vomiting. CONCLUSION: FOLFOX6 chemotherapy can decrease serum VEGF expression in patients with advanced colorectal cancer and enhance the curative effect with high safety, which is good for the improvement of patients' survival.

RESUMO OBJETIVO: Explorar o efeito da quimioterapia Folfox6 na expressão do fator de crescimento endotelial vascular sérico (VEGF) em pacientes com câncer colorretal avançado. MÉTODOS: Uma análise retrospectiva de 81 pacientes com câncer colorretal avançado que visitaram nosso hospital de março de 2014 a fevereiro de 2016 foi realizada. Todos os pacientes foram tratados com quimioterapia Folfox6. No dia 1, os doentes receberam oxaliplatina 100 mg / m2 ivgtt (2h), folinato de cálcio 200 mg/m2 ivgtt (2h), 5 fluorouracil 400 mg/m2 iv bolus e 5 fluorouracil 2.500 mg/m2 ivgtt (5h). O curso de tratamento foi de duas semanas e foram necessários quatro cursos de tratamento. Foram observadas as alterações nos níveis de VEGF e CRP e qualidade de vida antes e após quatro cursos de quimioterapia e avaliados os efeitos terapêuticos e reações adversas após a quimioterapia. RESULTADOS: Após o tratamento, a eficácia total da quimioterapia foi de 82,72% (67/81), com 24 casos em remissão completa, 25 casos em resposta parcial, 18 casos em doença estável e 14 casos em doença progressiva. Os níveis de CRP e VEGF após o tratamento foram significativamente inferiores aos do tratamento (5,69 ± 0,77) mg / L vs. (7,99 ± 1,36) mg / L; (443,26 ± 21,55) pg / mL vs. (542,83 ± 20,44) pg / mL] (P < 0,05). O grau de KPS após o tratamento foi significativamente maior do que antes do tratamento (57,84 ± 4,6 pontos) vs. (50,99 ± 3,73 pontos)] (P < 0,05). Entre eles, três casos desenvolveram erupção cutânea, cinco casos sofreram perda de cabelo e nove casos desenvolveram náuseas e vômitos. CONCLUSÃO: A quimioterapia Folfox6 pode, obviamente, diminuir a expressão de VEGF no soro em pacientes com câncer colorretal avançado e melhorar o efeito curativo com alta segurança, o que é bom para a melhoria da sobrevivência dos pacientes.

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.

Respuesta histológica completa a la neoadyuvancia en carcinoma gástrico avanzado: A propósito de un caso y revisión de la literatura / Histological complete response to neoadjuvant therapy in advanced gastric carcinoma: A case report and review of literature

La presente comunicación, describe el primer caso en el Instituto Regional de Enfermedades Neoplásicas "Luis Pinillos Ganoza" IREN Norte en la que una paciente con carcinoma gástrico avanzado ha mostrado respuesta histopatológica completa a neoadyuvancia. Se presenta una paciente mujer de 70 años con diagnóstico histopatológico de adenocarcinoma gástrico tubular moderadamente diferenciado, localmente avanzado con imágenes de adenopatías perigástricas asociadas y pérdida de la interfase entre tumoración gástrica, hilio hepático y vesícula biliar. Luego de 6 cursos de quimioterapia neoadyuvante con esquema FOLFOX - 4 al 80%, se obtiene una respuesta casi completa desde el punto de vista tomográfico; por ello a la paciente se le realiza gastrectomía subtotal distal más linfadenectomía D2 más gastroyeyunoanastomosis Billroth II término lateral tipo Hofmeister Finsterer, verificándose, al examen microscópico de la pieza operatoria, sólo gastritis crónica y aguda con áreas mucosas y cambios reactivos. No se observa neoplasia maligna viable. Ganglios linfáticos: 0/33. Paciente evoluciona favorablemente. A propósito del caso se hace una revisión de la literatura médica relevante actualizada

This communication describes the first case in the Regional Institute of Neoplastic Diseases "Luis Pinillos Ganoza" IREN North in which a patient with advanced gastric carcinoma showed complete response to neoadjuvant histopathologic. We describe the case of a patient woman of 70 years old with histopathologic diagnosis of moderately differentiated tubular gastric adenocarcinoma, locally advanced associated with images of perigastric lymphadenopathy and loss of the interface between gastric tumor, hepatic hilum and gallbladder. After 6 courses of neoadjuvant chemotherapy with FOLFOX scheme - 4 to 80%, an almost complete response from the point of tomographic view is obtained, so the patient is underwent to distal subtotal gastrectomy lymphadenectomy D2 more gastrojejunoanastomosis Billroth II termino lateral type Hofmeister Finsterer verifying on microscopic examination of surgical specimen only acute and chronic gastritis with mucous areas and reactive changes. No feasible malignancy is observed. Lymph nodes: 0/33. Commenting on the case, a review of recent relevant literature is realized

Establishment of patient-derived tumor xenograft (PDTX) models using samples from CT-guided percutaneous biopsy

This study aimed to investigate the feasibility of the establishment of a human cancer xenograft model using samples from computed tomography (CT)-guided percutaneous biopsy. Fresh tumor tissues obtained from 10 cancer patients by CT-guided percutaneous biopsy were subcutaneously inoculated into NOD-Prkdcem26Il2rgem26Nju (NCG) mice to establish human patient-derived tumor xenograft (PDTX) models. The formation of first and second generation xenografts was observed, and tumor volume was recorded over time. Tumor tissue consistency between the PDTX model and primary tumors in patients was compared using H&E staining and immunohistochemistry. Pharmacodynamic tests of clinically used chemotherapeutic drugs were conducted on second generation xenografts, and their effects on tumor growth and body weight were observed. CT-guided percutaneous biopsy samples were successfully collected from 10 patients with advanced cancers. The PDTX model was established in mice using tumor samples obtained from 4 cancer patients, including one small cell carcinoma sample, two adenocarcinoma samples, and one squamous cell carcinoma sample. The success rate was 40%. The obtained PDTX model maintained a degree of differentiation, and morphological and structural characteristics were similar to primary tumors. The pharmacodynamic test of chemotherapeutic drugs in the PDTX model revealed a therapeutic effect on tumor growth, as expected. CT-guided percutaneous biopsy samples can be effectively used to establish a PDTX model, and test these chemotherapy regimens.

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...

Farmacogenómica del tratamiento de primera línea en el cáncer gástrico: avances en la identificación de los biomarcadores genómicos de respuesta clínica / Pharmacogenomics of the first-line treatment for gastric cancer: advances in the identification of genomic biomarkers for clinical response to chemotherapy

Debido a la inespecificidad de los síntomas, el cáncer gástrico (CG) es diagnosticado frecuentemente en etapas avanzadas, lo que da cuenta de los altos índices de mortalidad debido a esta neoplasia a nivel mundial. El esquema de tratamiento adyuvante o neoadyuvante en los países occidentales incluye el uso de fluoropirimidinas citotóxicas y compuestos de platino formadores de aductos en el ADN. La respuesta clínica al tratamiento con estos fármacos depende principalmente de la sensibilidad del tumor, la cual a su vez está condicionada por el nivel de expresión de los blancos terapéuticos y de las enzimas de reparación del ADN. Sumado a esto, algunos polimorfismos de línea germinal en genes asociados al metabolismo y a la respuesta a estos fármacos, han mostrado asociación con respuestas pobres y con el desarrollo de eventos adversos, incluso con resultados fatales. La identificación de biomarcadores genómicos, en la forma de polimorfismos genéticos o la expresión diferencial de genes específicos asociados a la respuesta quimioterapeútica ha sido motivo de intensa investigación como base para la aplicación de la farmacogenómica en el establecimiento de una terapia farmacológica racional y personalizada del CG. Sin embargo, ante la eventual aplicación de la farmacogenómica en el ámbito clínico, es necesario establecer el valor pronóstico real de dichos biomarcadores mediante los estudios de asociación genotipo-fenotipo, así como su prevalencia en el contexto de cada población de pacientes. Estos aspectos son indispensables al evaluar la relación costo-efectividad de la introducción de los productos de la medicina genómica predictiva en el tratamiento del CG.

Gastric cancer (GC) is often diagnosed at later stages due to the lack of specificity of symptoms associated with the neoplasm, causing high mortality rates worldwide. The first line of adjuvant and neoadjuvant treatment includes cytotoxic fluoropyrimidines and platin-containing compounds which cause the formation of DNA adducts. The clinical outcome with these antineoplastic agents depends mainly on tumor sensitivity, which is conditioned by the expression level of the drug targets and the DNA-repair system enzymes. In addition, some germ line polymorphisms, in genes linked to drug metabolism and response to chemotherapy, have been associated with poor responses and the development of adverse effects, even with fatal outcomes in GC patients. The identification of genomic biomarkers, such as individual gene polymorphisms or differential expression patterns of specific genes, in a patient-by-patient context with potential clinical application is the main focus of current pharmacogenomic research, which aims at developing a rational and personalized therapy (i.e., a therapy that ensures maximum efficacy with no predictable side effects). However, because of the future application of genomic technologies in the clinical setting, it is necessary to establish the prognostic value of these genomic biomarkers with genotype-phenotype association studies and to evaluate their prevalence in the population under treatment. These issues are important for their cost-effectiveness evaluation, which determines the feasibility of using these medical genomic research products for GC treatment in the clinical setting.

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.

Trombosis venosa portal e hiperplasia nodular regenerativa hepática; posible efecto adverso asociado a bevacizumab y oxaliplatino / Portal vein thrombosis and nodular regenerative hyperplasia associated with the use of bevacizumab and oxaliplatin. Report of one case

Nodular regenerative hyperplasia (NRH) consists in diffuse transformation of the hepatic parenchyma into small regenerative nodules without fibrosis, secondary to vascular occlusion and flow alterations. This gives a nodular appearance to theliver, as there is atrophy and compensatory hypertrophy of hepatocytes. We reporta 69-year-old male who suffered of colon cancer and was treated with Oxaliplatin (OX) and Bevacizumab (B). During treatment with B the patient presented a partial thrombosis of the portal vein, that one year later became permeable. Esophageal varices were found in an upper digestive endoscopy. Hepatic tests were normal. Aliver biopsy was performed and informed nodular regenerative hyperplasia. Thus, the different factors that could explain this pathology are analyzed. B, a monoclonal antibody against vascular endothelial growth factor, reduces the anti-apoptotic, anti-inflammatory and survival effects produced by this factor, affecting the vascular protection of the endothelial cell. On the other hand, OX activates metalloproteinasesand depletes sinusoidal glutathione producing sinusoidal lesions. Thus, (OX) would be associated with sinusoidal obstruction and NRH sporadically. It is important to discuss the possible etiologic factors that can cause NRH reviewing the hepatotoxic effects caused by both drugs.

Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer

Cisplatin resistance remains one of the major obstacles when treating epithelial ovarian cancer. Because oxaliplatin and nedaplatin are effective against cisplatin-resistant ovarian cancer in clinical trials and signal transducer and activator of transcription 3 (STAT3) is associated with cisplatin resistance, we investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and wound healing assays, and Western blot analysis were used to compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming ability and greater inhibition on cell motility than cisplatin in ovarian cancer. Early in the time course of drug administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α, VEGF, survivin, and Bcl-XL, while oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3β. The STAT3 pathway responded early to platinum drugs associated with cisplatin resistance in epithelial ovarian cancer and provided a rationale for new therapeutic strategies to reverse cisplatin resistance.

Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: a pilot randomized clinical trial / Vitamina E na prevenção de neuropatia periférica induzida pela oxaliplatina: estudo clínico piloto randomizado

Oxaliplatin is one of the chemotherapy regimens most used for treating colorectal cancer. One of the main limitations to its use is induction of peripheral neuropathy. Previous studies have shown that vitamin E can reduce the incidence of peripheral neuropathy by 50%. This study aimed to assess the effectiveness of vitamin E for prevention of oxaliplatin-induced peripheral neuropathy.

Prospective, phase II, randomized pilot study developed at a university hospital in the Greater ABC region.

Patients were randomized five days before starting oxaliplatin treatment, to receive either vitamin E or placebo until the end of the chemotherapy regimen. The outcome was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 3, and specific gradation scales for oxaliplatin-induced peripheral neuropathy. Patients with colorectal and gastric cancer who had been scheduled to receive oxaliplatin-based chemotherapy were included. Both groups received calcium and magnesium supplementation before and after oxaliplatin infusions.

Eighteen patients were randomized to the vitamin E group and 16 to the placebo group. Cumulative incidence of 83% with peripheral neuropathy grades 1/2 was observed in the vitamin E group, versus 68% in the placebo group (P = 0.45). A trend towards more diarrhea was observed among patients who received vitamin E (55.6% vs. 18.8%; P = 0.06). There were no other significant differences in toxicity between the groups.

No significant decrease in the incidence of acute oxaliplatin-induced peripheral neuropathy was demonstrated through vitamin E use.

A oxaliplatina é um dos quimioterápicos mais utilizados no tratamento do câncer colorretal, sendo a indução da neuropatia periférica (NP) uma das principais limitações para o seu uso. Trabalhos anteriores demonstraram que a vitamina E poderia reduzir a incidência dessa neuropatia em 50%. Este estudo teve como objetivo avaliar a efetividade da vitamina E na prevenção da NP induzida pela oxaliplatina.

Estudo piloto prospectivo e randomizado de fase II desenvolvido em hospital universitário do Grande ABC.

Os pacientes foram randomizados para receber vitamina E ou placebo por cinco dias antes do início do tratamento com oxaliplatina e até o término do regime quimioterápico. O desfecho foi avaliado através dos Critérios Comuns de Toxicidade do Câncer versão 3 (CTCAE) e escalas específicas de gradação da NP induzida por oxaliplatina. Foram incluídos pacientes com câncer colorretal e gástrico programado para receber quimioterapia baseada em oxaliplatina. Ambos os grupos receberam suplementação de cálcio e magnésio antes e depois das infusões de oxaliplatina.

Dezoito pacientes foram randomizados para grupo da vitamina E e 16 para o grupo placebo. Observou-se incidência cumulativa de 83% das classes I/II de neuropatia periférica no grupo da vitamina E, contra 68% no grupo placebo (P = 0,45). Observou-se maior tendência à diarreia em pacientes que receberam vitamina E (55,6% versus 18,8%, P = 0,06). Não houve outras diferenças significativas quanto às toxicidades entre os grupos. ...

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.

Nuevas alternativas en el tratamiento del cancer gástrico avanzado / Treatment of advanced gastric cancer with oxaliplatin plus 5-fluorouracil/ leucovorin (FOLFOX-4 chemotherapy)

Background: Chemotherapy improves survival in advanced gastric cancer. However the most active combinations have a high level of toxicity that limits their use. Aim: To assess the response, toxicity and survival of patients with advanced gastric cancer, treated with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX-4 chemotherapy). Material and methods: Patients with stage IVgastric cancer, according to the American Joint Committee on Cancer or with relapsed disease and functional capacity 0-2 of the South West Oncology Group, were included. FOLFOX-4 chemotherapy was used as first or second line treatment. The response to treatment and survival were assessed. Results: Between 2003 and 2006, 29 patients (median age 52.5 years, 69 percent males) were treated. FOLFOX-4 was given as first line treatment in 65 percent patients and as second line in 35 percent. There was a complete response in 4.6 percent, partial response in 68 percent, stable disease in 20.6 percent and progression in 6.8 percent. Toxicity was observed in 51 percent of patients, that was hematological and non hematological grade 3/4 in 14 percent. Median survival was 12.5 months. Conclusions: FOLFOX-4 chemotherapy was active in advanced gastric cancer and had a low level of toxicity.

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