A pilot study evaluating the safety and toxicity of epirubicin, cisplatin, and UFT (ECU regimen) in advanced gastric carcinoma.

BACKGROUND: Best response rates have been achieved with three-drug regimens containing 5-FU in the treatment of advanced gastric cancer (AGC) and oral fluoropyrimidines are the best alternatives as substitutes for infusional 5-FU. This study aimed to evaluate the safety and toxicity of epirubicin, cisplatin, and UFT (ECU regimen) regimens in AGC outpatients. MATERIALS AND METHODS: Forty-one patients with AGC received epirubicin, cisplatin, and oral UFT plus leucovorin. Epirubicin 50 mg/m(2) and cisplatin 60mg/m(2) were administered on Day 1. Three hundreds (300) mg/m(2)/day UFT was administered with leucovorin at a fixed oral dose of 90 mg/day for 21 days, followed by a 7-day rest period. Cycles were repeated every 4 weeks. Performance status was either as 0 and 1. RESULTS: Among the 41 patients enrolled, complete and partial response was achieved in 7.3% and 36.6% of patients, respectively, with an overall response rate of 43.9%. Stable disease was observed in 34.1% of patients and 22% showed disease progression. Median time to progression was 5.2 months and median survival was 12.3 months. A median of 4 cycles (range: 1-6) of chemotherapy were administered. The main grade III-IV toxicities were nausea/vomiting (19.4%) and neutropenia (12.1%). Grade IV toxicities were gastric perforation and renal failure. CONCLUSION: ECU appears to be an effective regimen in the treatment of AGC, with acceptable tolerability and manageable toxicity. In three-drug regimens, substitution of infusional 5-FU by UFT offers the possibility of increased AGC outpatient compliance.

Message-adjusted network (MAN) hypothesis in gastro-entero-pancreatic (GEP) endocrine system.

Several types of communication coordinate body functions to maintain homeostasis. Clarifying intercellular communication systems is as important as intracellular signal mechanisms. In this study, we propose an intercellular network model to establish novel targets in GEP-endocrine system, based on up-to-date information from medical publications. As materials, two physiologic events which are Pavlov's sham-feeding assay and bicarbonate secretion into the duodenum from pancreas were explored by new biologic data from the literature. Major key words used in Pub-Med were modes of regulations (autocrine, paracrine, endocrine, neurocrine, juxtacrine, lumencrine), GEP cells, hormones, peptides and neuro-transmitters. In these two examples of physiologic events, we can design a model of network to clarify transmission of a message. When we take a simple, unique message, we can observe a complete intercellular network. In our examples, these messages are "food is coming" and "hydrogen ions are increasing" in human language (humanese). We need to find molecular counterparts of these unique messages in cell language (cellese). In this network (message-adjusted network; MAN), message is an input which can affect the physiologic equilibrium, mission is an output to improve the disequilibrium and aim is always maintenance of homeostasis. If we orientate to a transmission of a unique message we can distinguish that different cells use different chemical messengers in different modes of regulations to transmit the same message. This study also supports Shannon's information theory and cell language theories such as von Neumann-Patte principles. After human genome project (HU-GO) and protein organisations (HU-PO), finding true messages and the establishment of their networks (in our model HU-MAN project) can be a novel and exciting field in cell biology. We established an intercellular network model to understand intercellular communication in the physiology of GEP endocrine system. This model could help to explain complex physiologic events as well as to generate new treatment concepts.

Prognostic features and survival of inoperable hepatocellular carcinoma in Turkish patients with cirrhosis.

BACKGROUND: Primary hepatocellular carcinoma (HCC) is common in Turkey and its prognosis is poor. In the current study the authors analyzed the prognostic factors and survival in Turkish patients with inoperable HCC with cirrhosis. METHODS: Clinical and demographic data of 91 patients consecutively admitted to the authors' institute from 1988 to 2000 were reviewed. A univariate analysis was performed using the Kaplan-Meier method to identify predictors of survival and were compared using the Mantel log-rank test. Independent factors correlated with survival were determined using the Cox regression analysis. RESULTS: Cirrhosis was diagnosed in all patients. Coinfections with HCV and HBV were not observed. Overall median survival was 16.9 months. On univariate analysis, poor performance status (Eastern Cooperative Group); high alpha-fetoprotein (AFP); low albumin; high bilirubin; high alkaline phosphatase; high lactic dehydrogenase; high alanine and aspartate aminotransferase; high gamma-glutamyl transpeptidase; high platelet count; low prothrombin activity; hepatitis B surface antigen positivity; the presence of ascites, encephalopathy, and portal vein thrombosis; poor differentiation and diffuse type of tumor; and no treatment were associated with shorter survival. Multivariate analysis showed that only independent risk factors were related to performance status (Eastern Cooperative Group) at initial presentation and with pathologic characteristic of the tumor: abnormal AFP level. CONCLUSION: HCC occurred only in patients with liver cirrhosis. Survival time can be predicted from information collected by the physician at the initial assessment.

Colorectal cancer in young patients: characteristics and outcome.

Colorectal cancer is predominantly a disease of the elderly population, but this disease is unusual in patients 40 years of age or under, and controversy persists as to prognosis in this subset of patients. The aim of this study was to determine the clinicopathologic features and their impact on patients survival of colorectal cancer in patients aged 40 years or younger, and to compare them with those of older patients. The records of 466 patients with non-metastatic colorectal adenocarcinoma who were referred between 1991 and 1999 to the University of Istanbul, Institute of Oncology, following curative surgery were retrospectively analysed. The clinicopathologic features of 84 (18%) colorectal cancers (group A; male:female ratio 48:36) which occurred in patients aged 40 years or younger were compared with 382 colorectal cancers in older patients (group B; male:female ratio 194:188). Patient gender, performance status, T stage, N stage, TNM stage, histologic grade, location of tumor, lymphatic invasion, serum levels of LDH and CEA, and survival rates were compared as prognostic factors. There was no statistically significant difference between group A and group B with respect to patient gender, performance status, T stage, N stage, TNM stage, histologic grade, location of tumor, serum levels of LDH and CEA, and survival rates of colorectal cancers. The proportion of lymphatic invasion was present in 27% of patients in group A vs. 12% in group B. With median follow-up of 69 months, the overall 5-year survival rate was 61% in group A and 56% in group B. In the univariate survival analysis according to age groups (group A and B), advanced TNM stage, location of rectal tumor, presence of lymphatic invasion, and presence of high serum LDH and CEA levels are predictors of poorer survival in young patients with colorectal cancer. In the Cox-Regression analysis, location of tumor and TNM stage were determined as independent prognostic factors for survival. This study revealed no difference in clinicopathologic characteristics in patients with colorectal cancer aged 40 years or younger compared with those aged above 40 years. However, in patients aged 40 years or younger, distal location of tumor and advanced stage should be considered as poor prognostic factors for overall survival.

Adjuvant intraperitoneal chemotherapy with cisplatinum, mitoxantrone, 5-fluorouracil, and calcium folinate in patients with gastric cancer: a phase II study.

Gastric carcinoma remains one of the leading causes of cancer-related death in the world. Clinical studies have revealed that approximately two thirds of the patients seek treatment for early recurrence within the abdominal cavity. The aim of this phase II study was to evaluate the toxicity, feasibility, and efficacy of adjuvant intraperitoneal chemotherapy (IPCT) with cisplatin, mitoxantrone, 5-fluorouracil (5-FU), and folinic acid in patients with stage II-III gastric cancer. Patients with stage II and III gastric cancer aged between 15 and 70 years, after curative resection, with adequate liver, renal, and cardiac function were included in the study. The chemotherapy regimen consisted of cisplatin 60 mg/m2, mitoxantrone 12 mg/m2, 5-FU 600 mg/m2, and folinic acid 60 mg/m2, delivered intraperitoneally, diluted in 2 l normal saline. Intraperitoneal fluid was not drained. Each course of IPCT was repeated every 4 weeks for a total 6 cycles. Thirty-nine patients were enrolled in the study. Twenty-eight of the 39 patients (71.8%) completed six courses of the planned schedule. One patient (2.6%) died after a fourth cycle of IPCT from an undetermined reason. The major nonhematologic toxicity from IPCT was grade I-III nausea and/or vomiting experienced by 27 patients (69.2%). Twenty-four (61.5%) patients reported abdominal discomfort. Median follow-up was 23 (range: 3-105) months. Twenty-five patients (64.1%) were dead. Median disease-free survival and overall survival were 12 (CI 95%; 8.3-15.7 months) and 19 months (CI 95%; 10.5-27.5 months), respectively. The cumulative 5-year disease-free survival and overall survival were 24.7% and 30.7%, respectively. The regimen was generally associated with acceptable toxicity. However, adjuvant IPCT has similar survival rates in comparison to no adjuvant treatment; thus, it cannot be currently recommended outside the context of a clinical trial.