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Purpose Adjuvant chemotherapy improves survival of patients with gastric cancer. Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) was a phase III study comparing sequential FOLFIRI followed by docetaxel/cisplatin versus 5-fluorouracil monotherapy. The intensive regimen was not superior in terms of disease-free survival (DFS) and overall survival (OS). Methods The treatment was to be started within 8 weeks from surgery. This analysis evaluates the impact of time from surgery to chemotherapy start (TSC) on outcomes. Results Out of 1,106 randomized, 1,072 patients without major violations of eligibility criteria and receiving at least one treatment cycle were analyzed. Median TSC was 50 days. Chemotherapy was interrupted in 201 (18.8%) cases, whereas it was completed without or with modifications in 277 (25.8%) and 594 (55.4%), respectively. At a median follow-up of 56.9 months, 513 progressions and 472 deaths occurred. A longer TSC was significantly associated with longer DFS (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.89-1.00; p = 0.05) and OS (HR 0.91; 95% CI 0.86-0.97; p = 0.004), after adjustment for treatment arm, age, sex, primary tumor site, number of resected nodes, and tumor stage. Better treatment compliance was associated with improved survival. Conclusions Our findings suggest that longer TSC had at least no detrimental effect on DFS and OS, whereas treatment completion had a protective effect. Our findings need to be confirmed prospectively.

Environmental and electrical stress phases are commonly applied to automotive devices during manufacturing test. The combination of thermal and electrical stress is used to give rise to early life latent failures that can be naturally found in a population of devices by accelerating aging processes through Burn-In test phases. This paper provides a methodology to evaluate and compare the stress procedures to be run during Burn-In; the proposed method takes into account several factors such as circuit activity, chip surface temperature and current consumption required by the stress procedure, and also considers Burn-In flow and tester limitations. A specific metric called Stress Coverage is suggested summing up all the stress contributions. Experimental results are gathered on an automotive device, showing the comparison between scan-based and functional stress run by a massively parallelized test equipment; reported figures and tables quantify the differences between the two approaches in terms of stress.

Gemcitabine is considered the gold standard treatment for unresectable pancreatic adenocarcinoma. Intra-arterial drug administration had shown some interesting results in small phase II studies. In this study, patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or FLEC: 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arterially into celiac axis at a 3-week interval 3 times or 5-fluorouracil 400 mg/m2 plus folinic acid 20 mg/m2 for 5 days every 4 weeks for 6 cycles. The primary endpoint was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=0.036). Survival at 1 year increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=0.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both groups (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, the FLEC regimen given intra-arterially improved survival in patients with unresectable pancreatic adenocarcinoma.

Background: Some trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer. Patients and methods: Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m 2 day 1, LV 100 mg/m 2 as 2 h infusion and 5-FU 400 mg/m 2 as bolus, days 1 and 2 followed by 600 mg/m 2 /day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m 2 day 1, cisplatin 75 mg/m 2 day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm). Results: From February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85–1.17; P= 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82–1.18; P= 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively. Conclusions: A more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy. Clinical trial registration: ClinicalTrials.gov Identifier: NCT01640782.

Aims and Background The role of chemotherapy in locally advanced or metastatic gastric cancer has been controversial, but chemotherapy has recently been shown to relieve tumor-related symptoms, improve quality of life and prolong survival when compared with best supportive care. Furthermore, palliative chemotherapy is also cost-effective. “Second-generation” combination chemotherapy regimens were developed in the 1980s with high activity in advanced or metastatic gastric cancer (EAP, FAMTX, PELF, ECF). In randomized studies, EAP demonstrated no difference in activity but a significantly higher overall toxicity and toxic death rate than FAMTX, and the ECF (epirubicin, cisplatin, 5-fluorouracil) regimen gave a survival and response advantage, tolerable toxicity, better quality of life and was more cost-effective than FAMTX. Methods Sixty patients with locally advanced or metastatic gastric cancer were treated with the ECF regimen (21 weeks of 5-fluorouracil given by continuous infusion through a central line at 200 mg/m2 for 24-hr combined with cisplatin at 60 mg/m2 iv and epirubicin at 50 mg/m2 iv beginning on day 1 and repeated every 3 weeks for 8 courses). There were 42 males and 18 females, with a median age of 64 years (range, 40-74). The median performance status was 1. The histologic type was adenocarcinoma in 44 patients and undifferentiated carcinoma in 16 (27%). Three patients had locally advanced disease (5%) and 57 had metastatic disease (95%). Seven patients (12%) had received prior chemotherapy for advanced disease. Results All patients were assessable for toxicity and 55 for response (5 had insufficient treatment). Toxicity was mild or moderate, and there was no toxic death. Incidence of WHO toxicity ≥ 2 was nausea and vomiting in 3%, mucositis in 3%, leukopenia in 7%, anemia in 3%, and thrombocytopenia in 2%. Port-a-Cath toxicity was thrombosis in 4, dislocation in 2 and infection in 3 patients. Seven complete responses and 13 partial responses (overall response rate, 36%) were achieved, with a response rate of 39% in untreated and 17% in pretreated patients. Nine patients (16%) had stable disease and 26 (47%) progressive disease. Most patients felt symptomatically improved on ECF. Conclusions Our study confirms that the ECF regimen has a favorable pattern of toxicity and is feasible on an outpatient basis. However, it did not confirm the high response rate reported in other phase II trials.

Aims and background For the hospitalized cancer patient, time takes on a rhythm which is very different from the external reality. Based on the idea that time represents a fundamental dimension of human existence and is connected to future plans, time spent waiting and memories, we carried out this experience entitled “Life Sound” project. The objectives of the project were to experiment different and unusual ways of spending time in hospital in order to improve the quality of life of the hospitalized cancer patient, to help the patient adapt to the hospital environment, to encourage awareness of self and to give a different meaning to time spent in the hospital. In particular, we evaluated the reduction in the levels of anxiety, in psychological suffering and the improvement in communication. Methods We met with patients, family members, friends, volunteers and department personnel (doctors, psychologists, nurses) in a room in the Oncology and Hematology Department set aside specifically for recreation activities such as having a cup of tea while listening to music, talking, joking, listening to people's memories and celebrating birthdays, anniversaries and other special days. The study, which involved 109 patients, was carried out through the use of the questionnaire STAI-Y distributed before and after the event. Results The results showed a statistically significant difference in anxiety levels 2 hrs before participation (mean = 38.33) and 2 hrs after participation (mean = 34.77) in the program. This variation was also assessed based on gender, age, cancer stage, time since diagnosis and performance status but did not result in any statistically significant difference. Conclusions The “Life Sound” project encourages the emergence of positive feelings, of a renewed willingness to invest in personal and caring relationships, which are connected to the patient's ability to face this illness, and the opening of new channels of communication with family members and hospital staff.

We report a case of breast metastasis of signet ring cell gastric cancer clinically presented as a primary inflammatory carcinoma. Metastases to the breast are uncommon; review of the literature demonstrated only 300 cases. The clinical and radiographic features of the metastatic lesion were unlike those reported in the literature. Although a primary signet ring cell breast carcinoma was described, the pathologic patterns of the breast lesion, here reported, lead us to conclude this was a metastasis and not another primary tumor.

Gene therapy involves the introduction of foreign DNA into somatic cells to produce a therapeutic effect. The therapeutic gene is transferred into the tumor cells using a vector. Transfer may either be in vivo in which the DNA and vector are directly introduced into the body, or ex vivo, in which cells are removed from the body, transfected with DNA and then reintroduced into the patients. The mode of gene transfer can be classified into chemical, physical and viral (1). Viruses are the most popular vectors in clinical trials because they invade cells and manipulate the cell's machinery to make viral protein; but the immune response they provoke can rapidly destroy the viral vector or the infected cells, blocking production of the useful protein. Most nonviral vector fly under the radar of immune system, but most of them have not been as efficient as viruses in shuttling genes into cells and the genes that were delivered didn't remain active for long. Intra-arterial administration can have advantages over intravenous, and intralesion routes.

Unresectable biliary tract cancers have a very poor prognosis. No good systemic chemotherapeutic regimen is available. This study aimed to evaluated the activity and toxicity of a novel approach of combined loco-regional and systemic chemotherapy. Twenty four patients with advanced or metastatic biliary tumors were treated with epiadriamycin 50 mg/m2 and cisplatin 60 mg/m2 administered bolus in proper hepatic artery on day 1, combined with systemic continuous infusion of 5-fluorouracil 200 mg/m2/day, from day 1 to day 14, every 3 weeks. The overall response rate was 8/24 (33%), including one complete response and 7 partial responses (stable disease 46%, progression 21%). The treatment was well tolerated with a minimal hematological toxicity; the major clinical problem was the deep venous thrombosis related to central venous catheter, that occurred in 5 patients (21%). Median overall survival was 14,6 months and 1-year and 2-year survival were 54% and 38% respectively. Performance status improved in 33% of patients and weight gain more than 7% was observed in 17%. This novel combined loco-regional and systemic chemotherapeutic regimen is active and safe for advanced biliary tract cancer patients.

Gemcitabine is considered the gold standard treatment for unresectable pancreatic adenocarcinoma. Intra-arterial drug administration had shown some interesting results in small phase II studies. In this study, patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or FLEC: 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arterially into celiac axis at a 3-week interval 3 times or 5-fluorouracil 400 mg/m2 plus folinic acid 20 mg/m2 for 5 days every 4 weeks for 6 cycles. The primary endpoint was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=0.036). Survival at 1 year increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=0.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both groups (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, the FLEC regimen given intra-arterially improved survival in patients with unresectable pancreatic adenocarcinoma.

Objectives: This study evaluated the clinical activity and toxicity of combination chemotherapy with irinotecan and oxaliplatin in patients with advanced pancreatic cancer that had progressed despite ≧1 course of a gemcitabine-containing regimen. Methods: Thirty patients with metastatic pancreatic cancer and Karnofsky performance status ≧70 received oxaliplatin 60 mg/m2 on days 1 + 15 and irinotecan 60 mg/m2 on days 1 + 8 + 15 every 4 weeks. Patients were assessed on the basis of clinical benefit response, changes in serum tumour marker CA 19-9, objective tumour response, time to progressive disease (TTP), and survival. Results: Six patients (20%) had clinical benefit response (median duration of 7.2 months). CA 19-9 levels were reduced ≧50% from baseline in 8 patients (26%) and remained stable in 8 patients. CT scans revealed that 3 patients (10%) had a partial response and 7 (23%) had stable disease. Two patients (7%) were down-staged and underwent surgery. Median TTP was 4.1 months, median survival was 5.9 months and the 1-year survival rate was 23.3%. The most serious adverse events were grade 3–4 leukopenia in 2 patients (6%), grade 3 neuropathy in 2 (6%) and grade 3 diarrhoea in 1 (3%). Conclusion: Chemotherapy with irinotecan and oxaliplatin is an active and well-tolerated combination in patients with advanced pre-treated pancreatic cancer.

Aims and Background ocular melanoma tends to metastasize to the liver, sparing for a long time the rest of the organism. Therefore, a regional treatment is especially indicated. Methods eight patients with ocular melanoma metastatic to the liver were treated with intraarterial hepatic carboplatin-based chemotherapy at the dose of 300 mg/m2 once every two weeks at an outpatient clinic. All the patients were submitted to laparotomy with surgical implantation of an arterial port device through the gastroduodenal artery. Results the overall response rate was 38% with a median survival time of 15 months. The regimen was well tolerated and the principle toxicity was myelosuppression; any instance of hepatic and/ or cholangitic damage was reported. Conclusions Carboplatin seems suitable for intraarterial hepatic chemotherapy and active in ocular melanoma metastic to the liver.

Results: In results of genotyping groups of patients with breast cancer by allelle specific polymerase chain reaction in the real time mode, were observed in 3 patients have heterozygote mutation of BRCA1 5382insC (4.5%) presented possible “founder” mutation. Among them 1 patient had primary multiple form of breast cancer and 2 patients had hereditary disease history. Mutation of BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G and BRCA2 6174delT gene were not detected in all cases. Studied mutation was not observed in control group. Conclusion: Result of our study confirmed contribution of mutation 5382insC gene BRCA1 in developing of breast cancer in Uzbek population. Considering high penetration of disease in carrier of mutation BRCA1, is expedient include testing 5382insC mutation in screening program in breast cancer prophylactics in Uzbekistan.

Mastocytosis is a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells in skin, bone marrow, bone, gastrointestinal tract, liver, spleen and lymph nodes. Today, regarding its biological features, mastocytosis (with or without myeloid accompanying disorders) is considered to be a hematologic disease. The classification proposed by Metcalfe in 1991 is the most useful in caring for patients with mastocytosis. In this classification 4 groups are described: 1) indolent mastocytosis with or without extracutaneous involvement; 2) systemic mastocytosis with an associated hematologic disorder; 3) aggressive mastocytosis; 4) mast-cell leukemia. Cutaneous mastocytosis typically presents as urticaria pigmentosa or diffuse cutaneous mastocytosis and these patients usually have a benign course. On the contrary, systemic mastocytosis is a disease with an increased risk to develop an aggressive hematologic disorder. In these patients a second hematologic process, such as myeloproliferative or myelodysplastic syndrome or acute leukemia, may occur. These patients often present without skin involvement and they have a very poor prognosis. Mast cell is a medium-sized granulated cell releasing chemical mediators (histamine, heparin, protease and cytokines). Mast cells originate from pluripotent hemopoietic progenitor cells that express the CD34 antigen. Mast cells are present in the bone marrow and are distributed throughout the connective tissues. Recently a mast-cell growth factor (MGF) has been identified. Clinical symptoms occur from the release of chemical mediators and the pathologic infiltration of cells. Although no effective therapy for patients with Mastocytosis is known, some patients may benefit from corticosteroid and interferon alpha treatment. The present article gives an overview of current knowledge about the biology, heterogeneity and treatment of human mastocytosis.

A case of a 64-year-old man with eccrine carcinoma arising from hand skin is reported. At the time of diagnosis he showed bilateral pneumonic metastases. Although the patient underwent two systemic chemotherapy lines, he showed further progressive disease of the lung. For this reason a third chemotherapy line was started through thoracic stop-flow infusion. In this way, a five month stable disease had been achieved. The patient died 7 months later for progressive disease. The rarity of this disease, the uncertain treatment, the feasibility and efficacy of thoracic stop-flow infusion are underlined and further studies are suggested.

Intra-arterial hepatic chemotherapy (LAHC) results in significantly higher response rate than the best systemic treatment of liver metastases from colorectal cancer, but no survival advantage has to date shown because of extra-hepatic progression. From June 1991 to December 1994, twenty patients with hepatic metastases from colorectal cancer were enrolled. All patients underwent laparotomy for the placement of an intra-arterial catheter into the gastroduodenal artery connected with a subcutaneous port. All patients underwent cholecystectomy and biopsy of liver lesion to confirm metastatic disease. Locoregional schedule was: 5-fluorouracil (5FU) 500 mg/sqm, epirubicin (EPI) 13 mg/sqm, mitomycin-C (MMC) 7 mg/sqm, in bolus every 3 weeks. Systemic therapy consisted of leucovorin 500 mg/sqm, over 2 hours and 5FU 600 mg/sqm in bolus every week. Treatment was planned over a six month period. The complete response (CR) plus partial response (PR) rate was 50% of the entire group. The median survival was 18 months and 1- and 2- and 3-year survival rates were 71%, 38% and 20% respectively. Prior to chemotherapy, LDH value and % of liver involvement were the only significant prognostic parameters. Toxicity was absent or mild and no patient stopped treatment because of side effects. Combined systemic and IAHC is an effective treatment for liver metastases from colorectal cancer, with a mild or moderate toxicity. However, more trials are needed, to improve the control of the extrahepatic disease.

The authors describe five consecutive patients with testicular non Hodgkin lymphoma, evaluate the clinical and histological characteristics and underline the importance of a chemotherapy approach both at diagnosis and at relapse. A review of the literature is carried on and particularly about the prognostic factors, the correlation with Ebstein Barr virus and the more recent integrated therapeutical approaches.

The optimal management of primary gastric lymphomas has yet to be defined. In the past surgery was advocated as the optimal first step for patients with PGL. Recently, an increasing number of studies suggest that chemotherapy is as effective as surgery.Fourteen patients with PGL were treated with chemotherapy alone. For patients with low-grade lymphoma, chemotherapy consisted of mitoxantrone 5 mg/sqm on days 1 to 3. Treatment courses were administered every 3 weeks up to a maximum of 6 cycles. Patients with high-grade lymphoma received chemotherapy according to the CHOP schedule every 4 weeks up to a maximum of 6 cycles. Two patients with high-grade lymphoma were treated as low-grade lymphoma patients (one because of age and poor performance status, the other because she refused chemotherapy that would cause hair loss). Two patients with low-grade lymphomas who did not respond to mitoxantrone were crossed over to CHOP.All patients were evaluable for toxicity, 13 for response to therapy and survival. Toxicity was mild or moderate. Neither perforation nor hemorrhage was observed. Eleven patients achieved a complete remission (85%), 1 a partial remission (7.5%) and 1 underwent disease progression (7.5%). At a median follow-up of 12 months (range 4-44 months) all complete responders are alive and disease free.Although the number of evaluable patients is too small to draw any final conclusions, chemotherapy seems to be as effective as surgery in PGL, and stomach preservation improves the quality of life of the patients.

Primary bone non Hodgkin's lymphomas (PBL) are approximately 5% of extranodal lymphomas and 5% of all primary bone tumors. A standard treatment has not been codified yet. The most received only radiotherapy but recently it was introduced combined modality treatment with radiotherapy plus chemotherapy or chemotherapy alone. The authors describe two cases of high grade PBL that received combined treatment with chemotherapy (VACOP-B regimen and monochemotherapy with mitoxantrone respectively) and radiotherapy. The patients achieved complete remission and up to day are alive and disease free at 33 and 15 months from the diagnosis respectively.

Ovarian cancer is most frequently diagnosed at an advanced stage. In recent years there has been intense interest in the chemotherapy of this disease. About cisplatin, the most active agent in the treatment of advanced ovarian cancer, some questions are only partially answered, as the optimal dose, the duration of treatment, the role of ciplatin-based two-, three-, or four-drug regimens, the role of intraperitoneal therapy, the use of old and new drugs in cisplatin-resistant patients. Carboplatin is currently the most important cisplatin analogue with a toxicity pattern very different from that of the parent compound, but, up to date, the combination of these two drugs does not seem to be any better than standard chemotherapy. Among new drugs, three deserve particular attention: taxol, a natural produce from the bark of the Pacific yew Taxus brevifolia, taxotere, a taxoid obtained by semisynthesis from the needles of the European yew Taxus baccata and gemcitabine, a cytostatic agent with a close resemblance to cytosine-arabinoside. Anyway, new approaches must continue to be sought too: among these, probably gene therapy may offer the best mechanism to overcome both intrinsic and acquired drug resistance.

Thirty-three patients with microscopically verified primary or metastatic malignant pleural effusion were studied: 7 had malignant mesothelioma and 26 metastatic pleural disease. The treatment was based on biochemical and clinical studies which show a synergy between cytosine-arabinoside (Ara-C) and cisplatin. These drugs were instilled in the pleural cavity at the dose of 100 mg for Ara-C and 100 mg/m2 for cisplatin. The cavity was drained after 4 h. If it was possible, the treatment was repeated weekly for 3 times and, after a 6-week rest, it could be started again with the same schedule. The overall response rate (complete plus partial remissions) was 74%. Toxicity was mild or moderate. We conclude that the combination of Ara-C and cisplatin is well tolerated and produces a high response rate in the treatment of malignant pleural effusions.

38 patients with advanced breast adenocarcinoma were treated in a phase II study with 5-fluorouracil and high-dose folinic acid combined with cyclophosphamide and mitoxantrone. 6 patients had received prior chemotherapy for advanced disease, all with an anthracycline-containing regimen. Treatment was generally well tolerated. The most common side-effect was myelosuppression, with 1 toxic death due to leukopenia-related sepsis. 1 patient developed severe congestive heart failure 12 months from the end of therapy. 36 patients were evaluable for response. The overall response rate was 55%. Median duration of response was 8 months and median survival time was 16 months. This regimen warrants further investigations.

Two case reports and review of the literature. The authors describe one case of primary lymphoma and one case of secondary lymphoma of the bladder. They evaluate the differences, underline the rarity of the primitive type and make a review of the literature.

The authors describe two cases of nasopharynx and oropharynx carcinomas in treated non-Hodgkin lymphoma's patients. They evaluate pathogenetic hypotheses related to lymphoma, its treatment and some exogenous factors like smoke, alcohol, Epstein-Barr virus.

15 patients with primary or metastatic pleural effusion were studied: 2 had diagnosis of malignant mesothelioma and 13 of metastatic pleural disease. The treatment used was based on in vitro and in vivo studies which show a synergy between ARA-C and Cisplatin. These drugs were instilled in pleural cavity at the dose of 100 mg./m2 for Cisplatin and 100 mg. for ARA-C. The cavity was drained after 4 hours. The treatment was repeated weekly. All patients had not been previously treated with loco-regional therapy. The response rate was 93% with 10 loco-regional complete remissions (66%). The two patients with malignant mesothelioma achieved a complete remission. The overall toxicity was acceptable. We conclude that combination of Cisplatin and ARA-C is well-tolerated and produces a very high response rate in the treatment of malignant pleural effusions.

4197 Background: The prognosis of advanced biliary tract cancer (ABTC) is very poor. Common systemic chemotherapy (CHT) have been reported to produce transient partial remission only in a small proportion of patients (PTS). Aim of this study is to evaluate the effectiveness of regional CHT combined with systemic CHT in PTS with ABTC. Methods: From January 2000 to May 2003, we treated 26 PTS with the combination of intra-arterial CHT (epirubicin 50 mg/sqm and cisplatin 60 mg/sqm, infused bolus by angiographic catheter introduced in proper hepatic artery, with Seldinger technique, on day 1) and e.v. continuous infusion of 5-FU 200 mg/sqm/day, from day 1 to day 14. Cycles were repeated every 3 weeks. 13 PTS were male; median age was 65 years (49–75); performance status was 0–1 in 17 PTS, 2 in 9 PTS; all had hystological confirmed ABTC; 21 PTS had cholangiocarcinoma and 5 PTS had gallbladder carcinoma, with liver involvement > 50% in 10 and < 50% in 16 PTS; three PTS ha peritoneal involvement, 3 had pleural m...

Doxifluridine (5-dFUR) is a fluoropyrimidine derivative with a better therapeutic index than FU (Bajetta, Eur J Cancer, 1993). This study independently evaluated the activity of two different schedules of oral or i.v. 5-dFUR plus levo-Ieucovorin. Between April 1993 and September 1994, a total of 130 untreated (in an adjuvant and metastatic setting) pts with measurable colorectal cancer were randomized to 5-dFUR 750 mg/m2 p.o. on days 1→4 and levo-leucovorin 25 mg/dose p.o. two hours before 5-dFUR, repeated every 12 days (Arm A); or 5-dFUR 3000 mg/m2 as a one hour i.v. infusion for 5 consecutive days combined with levo-leucovorin 25 mg/dose i.v. immediately before 5-dFUR every 21 days (Arm B). The first response evaluation was made after 2 mos of treatment. The two arms were well balanced in terms ofage (median 61 yrs, range 31–80), sex (M/F: 69/61) and disease extension. A preliminary intent-to-treat analysis was made of 126 adequately treated pts (4 too early to evaluate), of whom 67 were in Arm A and 59 in Arm B. The response rates were 15% in Arm A (2 CR, 8 PR, 29 SD, 28 PD) and 39% in Arm B (5 CR, 15 PR, 15 SD, 21 PD). Toxicity included WHO grade 3 and 4 diarrhea in respectively 16% and 7% of Arm A and 16% and 15% of Arm B respectively. Mucositis was mainly observed in Arm B (grade 3 in 13% and grade 4 in 1%). The preliminary data confirm the good tolerability profile of both the oral and the i.v. schedule. The oral route seems to be promising and is interesting, because it could be benefit for pts suitable for home treatment. Moreover, this study confirms the efficacy of i.v. doxifluridine as a fast line therapy in advanced colorectal cancer. Data management by I.T.M.O. (ltalian Trials in Medical Oncology) Scietific Service.

Background The very limited efficacy of current chemotherapeutic strategies in LAPC, the pattern of metastatic spread largely confined to the upper abdominal organs within the arterial supply of celiac axis induced us to design this phase II study of locoregional intra-arterial chemotherapy. Purpose The aim of the present study was to evaluate the feasibility, the toxicity, the response rate and the real impact on survival of a new combination of drugs administered intra-arterially in the treatment of LAPC. Patients and methods From January 1994 to March 1995, twenty-five consecutive patients with LAPC were given 2 intra-arterial cycles of chemotherapy through a catheter in celiac axis introduced via the femoral artery, on days 1 and 22. The schedule was FLEC: 5 fluoruracil (5FU) 1000 mg/sqm; leucoverin (LV) 100 mg/sqm, epirubicin (EPI) 60 mg/sqm and carboplatin (CP) 300 mg/sqm: each drug was infused over a period of 10 minutes and only one day of hospitalization was necessary for each cycle. After 2 cycles when we obtain a partial response (PR) or a stable disease (SD), other 2 cycles were planned. Results A total of 74 courses of chemotherapy were administered with a mean of 2.9 for each patient (1–5). 23 patients are evaluable for response: 10/23 patients had a PR (43%) evaluated by ct-scan, 14/23 had a decrease of Ca 19-9 (61%),14/23 had an improvement in quality of life (61%). Grade 3/4 hematological toxicity was observed in 5/23 (22%); grade 2/3 gastrointestinal toxicity in 2/23 (9%); alopecia in 2/23 (9%). One sudden death was observed in a patient on day 23 after the third cycle. No complications related to angiographic procedure was noted. At a median follow up of 4 months (1–13), the median survival is 5.6 months and 1-year survival rate is 51% and 9% for responders and non responders respectively. Conclusions This study showed that the FLBC combination given through a celiac axis infusion is well tolerated and active and may become an important strategy both in a palliative and in a preoperative setting in patients with pancreatic carcinoma.