TERT gene harbors multiple variants associated with pancreatic cancer susceptibility.

A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.

Chemotherapy in the last 30 days of life of advanced cancer patients.

PURPOSE: Chemotherapy near the end of life is an issue frequently discussed nowadays, but literature is generally poor. We analyzed patients with cancer who received chemotherapy in their last month of life. METHODS: The study involved all patients treated in our oncological department between 2010 and 2012; our attention focused on patients receiving chemotherapy in their last month of life. The hematologic malignancies are excluded. RESULTS: During the covered period, 2164 pts received chemotherapy, 162 received chemotherapy in their last month of life (24.3 %). The median age of this subgroup was 67.8 years, and median Eastern Cooperative Oncology Group (ECOG) performance status was 2. One hundred and five patients (64.8 %) were males. All patients presented a metastatic disease. Causes of death are as follows: 64.8 % progressive disease, sudden death in 4.9 %, toxicity in 3.1 %, and not available in 27.2 %. CONCLUSIONS: Twenty-four percent of patients treated with chemotherapy received their last regimen within 1 month of death. Percentage is in line with existing results. It is commonly acknowledged that age, performance status, tumor sensitivity, survival prognosis, and comorbidities should be considered in every chemotherapy decision-making; nevertheless, some studies show that age is not a crucial factor. At present, individual clinician is the only predictor for continuing chemotherapy in the last 4 weeks of life. Although appropriateness criteria were applied, patients were submitted to chemotherapy within 1 month of life; we hope that development of simultaneous care could help in end-life decision-making.

Prognostic factors in gemcitabine-cisplatin polychemotherapy regimens in pancreatic cancer: XPD-Lys751Gln polymorphism strikes back.

The use of platinated agents in combination chemotherapy regimens for advanced pancreatic cancer is controversial owing to the lack of an outstanding impact on the outcome and a substantial increase in hematologic and extra-hematologic toxicities. Pharmacogenetic studies to identify patients who could benefit most from such therapies are urgently needed. The Xeroderma-Pigmentosum group-D polymorphism at codon-751 (XPD-Lys751Gln) emerged as the most significant independent predictor for death- and progression-risk in our previous study on functional polymorphisms in 122 advanced pancreatic cancer patients treated with cisplatin-docetaxel-capecitabine-gemcitabine and cisplatin-epirubicin-capecitabine-gemcitabine (or EC-GemCap). To confirm the prognostic role of this variable, we further evaluated the correlation of XPD-Lys751Gln with outcome in another 125 patients treated with the same regimens, and 90 treated with gemcitabine monotherapy. Genotyping was successfully carried out in the vast majority of DNA samples. Genotype frequencies followed Hardy-Weinberg equilibrium, and XPD-Lys751Gln was associated with differential progression-free and overall-survival. Multivariate analysis confirmed its prognostic significance in platinum-based regimens. In particular, XPD-Gln751Gln was significantly associated with risk of death (hazard ratio, HR = 1.7, 95% confidence interval [CI], 1.1-2.6, p = 0.011) and risk of progression (HR = 1.7, 95% CI, 1.1-2.5, p = 0.013). No correlation was observed in gemcitabine monotherapy-treated patients. The analysis of DNA damage using extra-long-PCR in lymphocytes supported the association of XPD-Gln751Gln with greater resistance to cisplatin-induced damage. The increasing evidence of XPD-Lys751Gln impact on the outcome of gemcitabine-cisplatin-based polychemotherapy leads to plan prospective studies to validate the role of this polymorphism as a new tool for optimization of the currently available treatments in pancreatic cancer.

Gemcitabine-capecitabine plus intra-arterial epirubicin-cisplatin in pretreated pancreatic cancer patients: a phase I study.

BACKGROUND: Gemcitabine plus capecitabine are active in patients (pts) with advanced pancreatic cancer (APC). Intra-arterial chemotherapy showed activity and low toxicity. Combination of systemic and intra-arterial chemotherapy was investigated. PATIENTS AND METHODS: Patients with APC, progressed after a first-line chemotherapy, were included. Fixed doses of epirubicin 35 mg/m(2) and cisplatin 42 mg/m(2) intra-arterially every 28 days, and capecitabine 650 mg/m(2) twice a day on days 2-15; gemcitabine systemically in increasing doses on day 2. The purpose was to find maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT). RESULTS: Fifteen patients were enrolled. DLT occurred at 1300 mg/m(2) of gemcitabine and consisted of myelotoxicity (grade 4 febrile neutropenia and grade 4 thrombocytopenia). CONCLUSION: Limiting toxicity was hematological. For further studies intra-arterial epirubicin 35 mg/m(2) and cisplatin 42 mg/m(2); systemic gemcitabine at 1,000 mg/m(2) on day 2, and capecitabine at 650 mg/m(2) twice a day PO on days 2-15 are suggested.

Single nucleotide polymorphisms and clinical outcome in patients with biliary tract carcinoma treated with epirubicin, cisplatin and capecitabine.

BACKGROUND: Biliary tract carcinoma (BTC) is a rare highly malignant neoplasia. Polymorphisms at the xeroderma pigmentosum group D (XPD), excision repair cross-complementing group-1 (ERCC1) and X-ray repair cross complementing group 1 (XRCC1) genes were evaluated and correlated with clinical outcome. PATIENTS AND METHODS: Thirty-three patients with BTC were treated with intravenous or intra-arterial cisplatin and epirubicin and oral capecitabine. The ERCC1-C118T, XPD-Asp312Asn, XPD-Lys751Gln and XRCC1-Arg399Gln polymorphisms were studied. RESULTS: A partial response (PR) occurred in 6 patients. The median progression-free (PFS) and overall survival (OS) were 4.8 and 18.9 months, respectively. No significant correlations were observed between response, PFS and OS in patients grouped according to all the studied polymorphisms. The analysis of survival starting from diagnosis resulted in a significant association of the XRCC1-Arg399Arg variant with a shorter survival. CONCLUSION: A role of the XRCC1-Arg399Gln polymorphism as a possible prognostic factor in patients affected by BTC is suggested.

Sociodemographic, clinical, and psychological characteristics identify groups of Italian cancer patients with high rates of unmet needs.

PURPOSE: Although an optimal goal remains the routine assessment of unmet needs of all patients with cancer, particular attention should be paid to those groups of patients with characteristics known to be more frequently associated with unmet needs in general or with specific areas of need. This report aims to describe the sociodemographic, clinical, and psychological characteristics associated with higher unmet needs in Italian cancer patients. METHODS: A total of 835 cancer patients from different care settings (ward, day hospital, follow-up ambulatory, rehabilitation unit, and palliative care) filled out the Needs Evaluation Questionnaire (NEQ), the Psychological Distress Inventory, and the Sense of Coherence Scale. Association of NEQ scores with the clinical and demographic variables were tested using analysis of variance. RESULTS: Higher NEQ total score was associated with lower educational level, inpatient care setting, radiotherapy treatment, psychological distress, and lower resilience trait sense of coherence. Different predictors were identified for different areas of unmet needs. Care setting, psychological distress, and resilience trait were the strongest indicators of unmet needs in every area: information/communication, assistance/care, material needs, relational needs, and psychoemotional support. CONCLUSIONS: Clinicians should consider that inpatients with a high distress and a low resilience trait sense of coherence represent a group of cancer patients to be investigated with particular attention regarding unmet needs.

Pet therapy effects on oncological day hospital patients undergoing chemotherapy treatment.

BACKGROUND: Pet therapy is utilised to improve the quality of life of patients with chronic diseases. The impact of AAA (animal-assisted activities), a kind of pet therapy, on oncological patients submitted to chemotherapy was evaluated. PATIENTS AND METHODS: Two groups of patients receiving chemotherapy with (experimental group) or without AAA (control group) were compared. The 2 participating dogs have been trained by a cynophilist behaviourist and examined by a veterinarian. Before and after chemotherapy both groups of patients were asked to fill out a A.De.Ss.O. test questionnaire, a simplified Italian version of Kellner's Symptom Questionnaire. Arterial blood pressure, heart rate and arterial oxygen saturation were recorded. RESULTS: Depression improved only in the AAA group (p=0.01). Arterial oxygen saturation increased in the experimental group (p=0.004), while it decreased in the controls. CONCLUSION: AAA during chemotherapy reduces depression of patients and increases their arterial oxygen saturation.

Capecitabine plus hepatic intra-arterial epirubicin and cisplatin in unresectable biliary cancer: a phase II study.

UNLABELLED: The aim of the present study was to evaluate the activity of hepatic intra-arterial infusion of epirubicin and cisplatin combined with oral capecitabine, in patients with unresectable biliary carcinomas. PATIENTS AND METHODS: Twenty patients were treated by bolus infusion of epirubicin 50 mg/m2 and cisplatin 60 mg/m2 in the hepatic artery on day 1, combined with oral capecitabine 1000 mg/m2 bid, from day 2 to day 15. RESULTS: Partial responses (PR) were observed in 6 patients (31.5%), stable disease (SD) in 9 (47.5%) and progression (PD) in 4 (21%). The median progression-free and overall survival periods were 11.6 and 18.0 months, respectively, and 1-year survival was 74%. One patient died after the first cycle because of G4 diarrhea. The other patients had good tolerance, with minimal hematological toxicity and only 1 G3 vomiting. CONCLUSION: This combined intra-arterial and oral approach to patients with biliary carcinomas was found to be active and safe and seems to produce an encouraging survival response.

Adjuvant intra-arterial 5-fluoruracil, leucovorin, epirubicin and carboplatin with or without systemic gemcitabine after curative resection for pancreatic adenocarcinoma.

BACKGROUND: The role of adjuvant therapy in pancreatic cancer remains controversial. Gemcitabine given systemically seems to be effective; intra-arterial chemotherapy (IAC) has a deep rationale. PATIENTS AND METHODS: The goal was to evaluate the impact of postoperative IAC followed or not by systemic gemcitabine in patients after curative resection for pancreatic adenocarcinoma. 5-fluoruracil 750 mg sq m(-1), leucovorin 75 mg sq m(-1), epirubicin 45 mg sq m(-1), carboplatin 225 mg sq m(-1) were administered every 3 weeks into celiac axis for three cycles (FLEC regimen), then gemcitabine at the dosage of 1 g sq m(-1) on days 1, 8 and 15 every 4 weeks for 3 months (FLECG regimen). RESULTS: Forty-seven patients entered the study. The first 24 received only IAC (FLEC regimen), the other 23 received the same intra-arterial regimen followed by systemic gemcitabine (FLECG regimen). After a median follow-up of 16.9 months, 29 patients recurred (61.7%). Median disease free survival (DFS) was 18 months and median overall survival (OS) was 29.7 months. One-year DFS was 59.4% and 1-year OS was 75.5%. Main grade 3 toxicity related to IAC was only nausea/vomiting in 4%; regarding gemcitabine, grade 3 toxicities were anaemia 8%, leukopenia 8%, thrombocitopenia 17%, nausea/vomiting 4%. CONCLUSIONS: FLEC regimen with or without gemcitabine is active with a very mild toxicity and results are very encouraging in an adjuvant setting.

Hepatic arterial chemotherapy with oxaliplatin, folinic acid and 5-fluorouracil in pre-treated patients with liver metastases from colorectal cancer.

BACKGROUND: Hepatic arterial chemotherapy (HAC) is an effective treatment of liver metastases from colorectal cancer (CRC). Phase I and II studies have already shown the feasibility and efficacy of intra-arterial oxaliplatin (OXA). PATIENTS AND METHODS: Twenty-one pre-treated patients with liver metastases who received HAC with OXA/folinic acid (FA)/5-fluorouracil (5-FU) at our Division between March 2000 and November 2003, were clinically examined. Most patients were heavily pre-treated with two or more systemic chemotherapeutic regimes. All patients received a percutaneously implanted catheter into the hepatic artery through femoral or transaxillary access. Treatment was administered every 14 days: OXA 100 mg/m2 as a 12-hour infusion on day 1; FA 100 mg/m2 as a 2-hour infusion on days 2 and 3; 5-FU 2600 mg/m2 as a continuous infusion on days 2 and 3. RESULTS: Grade 3-4 toxicities were: asthenia (2 out of 21), transaminase elevation (2 out of 21) and pain (2 out of 21), nausea and vomiting (1 out of 21), neutropenia (1 out of 21), thrombocytopenia (1 out of 21) and neurotoxicity (1 out of 21). Main dose limiting toxicity was right upper quadrant pain. Response rates were: 5% complete response, 19% partial response, 28% stable disease and 48% progressive disease. Two patients became operable and underwent complete resection of liver disease. The median overall survival was 36.1 months. Two-year and 3-year survival rates were 62% and 52%, respectively. CONCLUSION: This regimen is feasible with low toxicity and with an encouraging overall tumor growth control (52%) in a subset of heavily pre-treated patients. Intra-arterial OXA/FA/5-FU should be considered for the treatment of patients pre-treated with systemic chemotherapies with liver metastases from CRC.

Intra-arterial infusion of 5-fluorouracil, leucovorin, epirubicin and carboplatin (FLEC regimen) in unresectable pancreatic cancer: results of a ten-year experience.

UNLABELLED: The final results of a new regimen given intra-arterially for unresectable pancreatic cancer (UPC) are presented. PATIENTS AND METHODS: From January 1994 to January 2006, 5-fluorouracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2 and carboplatin 300 mg/m2 were administered every 3 weeks into the celiac axis (CA) angiografically (FLEC regimen) to 211 patients with UPC. RESULTS: Seven hundred and sixty-four cycles were administered. Grade 3-4 hematological toxicity was observed in 24%; ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%; grade 3 alopecia in 15%. One sudden death, a pre-infarction angina and a transitory ischemic attack were observed. No complications related to the angiographic procedure took place, but three tunica intima dissections of the iliac artery occurred; 7.6% of patients with partial responses and 50.7% with stable disease were observed. Two hundred and one patients have died; median overall survival was 9.2 months: 10.5 and 6.6 for stage III and IV, respectively. CONCLUSION: The FLEC regimen given intra-arterially is well-tolerated and effective in patients with UPC.

Intra-arterial chemotherapy: a safe treatment for elderly patients with locally advanced breast cancer.

UNLABELLED: The feasibility, toxicity and local response rates of intra-arterial chemotherapy with 5-fluorouracil, epirubicin and mitomycin in patients over 75 years with locally advanced breast cancer was evaluated. PATIENTS AND METHODS: Ten patients were treated by the transfemoral Seldinger technique, with the catheter tip placed into the internal mammary artery. In order to evaluate the vessels perfusing the tumor, blue dye solution was infused before drug administration. The patients received 5-fluorouracil 750 mg/m2, epirubicin 30 mg/m2 and mitomycin 7 mg/m2 by bolus infusion. RESULTS: All patients were evaluated for toxicity and response. Twenty-two cycles were administered. The toxicity was mild and did not influence the patients' quality of life; the compliance was excellent. A response rate of 80% (8 out of 10) was obtained; the median overall survival was 33.5 months; no patient had local recurrence. CONCLUSION: Intra-arterial chemotherapy is an effective and safe treatment for locally advanced breast cancer in the elderly.

Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk.

The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk.

AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients.

Pancreatic ductal adenocarcinoma (PDAC) patients have the highest risk of developing cachexia, which is a direct cause of reduced quality of life and shorter survival. Novel biomarkers to identify patients at risk of cachexia are needed and might have a substantial impact on clinical management. Here we investigated the prognostic value and association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia in PDAC. Genotyping was performed in DNA from blood samples of a test and validation cohorts of 151 and 152 chemo-naive locally-advanced/metastatic PDAC patients, respectively. The association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia as well as the correlation between cachexia and the candidate polymorphisms and overall survival were analyzed. Akt expression and phosphorylation in muscle biopsies were evaluated by specific ELISA assays. SELP-rs6136-AA and AKT1-rs1130233-AA/GA genotypes were associated with increased risk of developing cachexia in both cohorts (SELP: p = 0.011 and p = 0.045; AKT1: p = 0.004 and p = 0.019 for the first and second cohorts, respectively), while patients carrying AKT1-rs1130233-GG survived significantly longer (p = 0.002 and p = 0.004 for the first and second cohorts, respectively). In the multivariate analysis AKT1-rs1130233-AA/GA genotypes were significant predictors for shorter survival, with an increased risk of death of 1.7 (p = 0.002) and 1.6 (p = 0.004), in the first and second cohorts, respectively. This might be explained by the reduced phosphorylation of Akt1 in muscle biopsies from patients harboring AKT1-rs1130233-AA/GA (p = 0.003), favoring apoptosis induction. In conclusion, SELP and AKT1 polymorphisms may play a role in the risk of cachexia and death in PDAC patients, and should be further evaluated in larger prospective studies.

A polymorphism in the promoter is associated with EZH2 expression but not with outcome in advanced pancreatic cancer patients.

AIM: EZH2 expression is a prognostic marker in radically resected pancreatic ductal adenocarcinoma (PDAC) patients. Here we investigated its role in locally advanced/metastatic patients, as well as candidate polymorphisms. MATERIALS & METHODS: EZH2 expression and polymorphisms were evaluated by quantitative reverse transcription PCR in 32 laser microdissected tumors, while polymorphisms were also studied in blood samples from two additional cohorts treated with gemcitabine monotherapy (n = 93) or polychemotherapeutic regimens (n = 247). RESULTS: EZH2 expression correlated with survival and with the rs6958683 polymorphism in the first cohort of patients, but this polymorphism was not associated with survival in our larger cohorts. CONCLUSION: EZH2 is a prognostic factor for locally advanced/metastatic PDACs, while candidate polymorphisms cannot predict clinical outcome. Other factors involved in EZH2 regulation, such as miR-101, should be investigated in accessible samples in order to improve the clinical management of advanced PDAC.

A single nucleotide polymorphism in EZH2 predicts overall survival rate in patients with cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a deadly disease arising from the malignant transformation of cholangiocytes. Enhancer of zeste homolog 2 (EZH2) is overexpressed in poorly differentiated CCA. Functional single nucleotide polymorphisms (SNPs) in this gene may affect the role of EZH2 in cholangiocarcinogenesis and chemoresistance. The aim of the current study was to evaluate the correlation between EZH2 SNPs and clinical outcome. Using PROMO3.0, GeneCard and MicroSNiper, 4 EZH2 SNPs with functional relevance in CCA were selected in silico. These SNPs were studied in genomic DNA extracted from the blood samples of 75 patients with advanced CCA, who were treated with epirubicin-cisplatin-xeloda (ECX regimen). SNP genotyping was performed with specific PCR assays. The rs887569 TT genotype was correlated with a significantly longer overall survival (OS; TT vs. CT-CC, P=0.026). Moreover, the TT genotype revealed a trend toward a significant association with a reduced risk of mortality (HR, 0.59; 95% CI, 0.33-1.05; P=0.075), by multivariate analysis. These results support future studies on the role of rs887569 EZH2 SNP as a possible predictive marker of OS in advanced CCA patients.

Genetic susceptibility to pancreatic cancer and its functional characterisation: the PANcreatic Disease ReseArch (PANDoRA) consortium.

Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n=86), chronic pancreatitis (n=272) and 3847 healthy controls have been collected. As a collective effort of the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going.

Association between DNA-repair polymorphisms and survival in pancreatic cancer patients treated with combination chemotherapy.

AIM: This multicenter study evaluated the association of 11 candidate polymorphisms in eight genes with outcome of pancreatic cancer patients treated with the equivalent polychemotherapeutic regimens: cisplatin/epirubicin/capecitabine/gemcitabine, cisplatin/docetaxel/capecitabine/gemcitabine and gemcitabine/capecitabine plus epirubicin/cisplatin intra-arterial infusion. PATIENTS & METHODS: Towards this end, polymorphisms were assessed in DNA from 122 pancreatic cancer stage-III/IV patients, and their associations with toxicity/response and progression-free survival (PFS) and overall survival were evaluated using Pearson-χ(2) and log-rank test. RESULTS: Patients harboring XPD Gln751Gln, XPD Asp312Asn + Asn312Asn or XRCC1 Arg399Gln + Gln399Gln genotypes had a worse prognosis. XPD Gln751Gln (hazard ratio: 1.9; p = 0.003), as well as a combination of over two risk genotypes (hazard ratio: 2.7; p < 0.001), emerged as independent predictors for death risk at multivariate analysis. No correlations were observed with toxicity. Conversely, XPD Gln751Gln was associated with shorter PFS, while the lack of association with overall survival/PFS in gemcitabine monotherapy-treated patients suggested its role only for platinum-based regimens. CONCLUSION: Polymorphisms of DNA-repair genes appear to be candidate biomarkers of primary resistance to gemcitabine/cisplatin-based polychemotherapeutic regimens. The relatively small sample size, coupled with the retrospective and exploratory design of the present study, imply that these results should be considered as hypothesis generators, and should be further evaluated in larger and adequately designed retrospective/prospective studies.

Prognostic factors in patients with advanced pancreatic adenocarcinoma treated with intra-arterial chemotherapy.

OBJECTIVES: The aim of this study is to identify the prognostic factors of a large group of patients with pancreatic cancer who underwent the same regimen of intra-arterial chemotherapy. METHODS: 5-fluorouracil (1000 mg/m2), leucovorin (100 mg/m2), epirubicin (60 mg/m2), and carboplatin (300 mg/m2) were administered every 3 weeks into celiac axis (FLEC regimen). Kaplan-Meyer survival curve for univariate analysis and Cox regression model for multivariate one were used to determine factors predictive of survival. RESULTS: Data of 211 patients with advanced pancreatic cancer who underwent FLEC regimen were analyzed. Eighty-nine had locally advanced disease, and 112 had distant metastases. Median overall survival was 9.2 months. In both univariate and multivariate analyses, pain reduction after treatment (< or =30% of baseline level vs >30%; overall survival, 7.6 vs 11.5 months), stage of disease (III vs IV; overall survival, 10.5 vs 6.6 months), and number of administered cycles (< or =3 vs >3; overall survival, 5.9 vs 12.3 months) were significant and independent predictors of survival. CONCLUSIONS: Pain reduction, stage of disease, and number of administered cycles are independent prognostic factors of overall survival in a multivariate analysis of patients with advanced pancreatic cancer receiving FLEC regimen intra-arterially.