Tacrolimus (FK506)-based dual versus triple therapy following liver transplantation.
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Adolescent↗
Biomedical subjects
E Baldini
Publications and source records attributed to E Baldini.
Brequinar sodium and liver hemoperfusion in xenotransplantation.
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Animals↗
Primary chemotherapy in locally advanced breast cancer (LABC): effects on tumour proliferative activity, bcl-2 expression and the relationship between tumour regression and biological markers.
The rate of tumour cell proliferation evaluated by the [3H]-thymidine labelling index ([3H]-dT-LI) is known to be an independent prognostic factor in patients with operable breast cancer and significantly predicts the response to chemotherapy in patients with advanced disease. In locally advanced breast cancer (LABG), we examined whether chemotherapy induced modifications in [3H]-dt-LI, and bcl-2 expression and their relationship with tumour regression and prognosis. 70 LABC patients received three courses of primary chemotherapy (FEC: 5-fluorouracil 600 mg/m2, epidoxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2, followed by surgery and subsequent adjuvant chemotherapy consisting of three courses of FEC alternated with three courses of CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, 5-fluorouracil 600 mg/m2). Tumour biological markers were evaluated on diagnostic biopsy, before primary chemotherapy and at surgery. Tumour cell proliferation was determined by [3H]-dT-LI, whilst bcl-2 expression was examined by immunohistochemical staining. The overall response rate to primary FEC was 74.3% (95% confidence interval 57.6-83.2%). The response rate correlated with high [3H]-dT-LI: 88% (29/33) of patients with high [3H]-dT-LI achieved an objective response compared with 62% (23/37) of patients with low [3H]-dT-LI (P = 0.014). The 3 patients achieving a pathological complete response after induction treatment had high proliferative tumours. The highest 2-year relapse free survival (66.6%) was observed in patients with low [3H]-dT-LI after primary chemotherapy. The median bcl-2 expression values before and after primary chemotherapy were 0% (range 0-80) and 30% (range 0-90), respectively (P = 0.03). Our data indicate that primary chemotherapy can modulate tumour cell kinetics and apoptosis-related genes. Pretreatment proliferative activity correlated with tumour response, whilst post-treatment [3H]-dT-LI correlated with relapse free survival.
Adult↗
Epirubicin/vinorelbine as first line therapy in metastatic breast cancer.
This study was aimed at investigating the toxicity and activity of the combination epirubicin and vinorelbine in chemotherapy-naive patients with metastatic breast cancer. Fifty-one patients with measurable or evaluable metastatic breast cancer entered the study. The regimen consisted of epirubicin 90 mg/m2 as a slow i.v. infusion on day 1, followed by vinorelbine 25 mg/m2 by 30-minute intravenous infusion on days 1 and 8; the courses were repeated every 21 days for a maximum of 8 cycles. All the patients were assessable for toxicity and 47 were evaluable for response according to the World Health Organization (WHO) criteria. Objective responses were observed in 33 out of 47 evaluable patients (70.2%; 95% C.I. 55.1%-82.6%) with 4 complete (8.5%) and 29 partial responses (61.7%); 11 patients had stable disease (23.4%) and 3 patients progressed while on treatment. The median time to progression was 10 months (range 1-21) and the median overall survival was 23 months (range 2 - 32+). Neutropenia was the most frequent toxicity: a grade 4 neutropenia (WHO) was reported in 70% of 252 courses with a median duration of 3 days (range 1-6). Seventeen episodes of febrile neutropenia were observed but only 1 patient required hospital admission. Other hematologic toxicities were negligible. One patient experienced a paralytic ileus requiring hospitalization; no peripheral neuropathy such as muscle weakness or paresthesia was observed. No treatment-related cardiotoxicity was reported. The encouraging response rate achieved with epirubicin/vinorelbine, the easily manageable toxicities of the combination, and its feasibility in an outpatient setting make this combination worthy of further comparative trials with standard regimens.
Adult↗
Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung cancer (NSCLC): a FONICAP randomized phase II study. Italian Lung Cancer Task Force (FONICAP).
In the present multicentre randomized phase II trial, the activity and toxicity of three platinum-based combination regimens for the treatment of advanced non-small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP (mitomycin-C 6 mg m(-2) on day 1, vindesine 3 mg m(-2) on days 1 and 15, and cisplatin 80 mg m(-2) on day 1 every 28 days), PIN (cisplatin 80 mg m(-2) day 1, ifosfamide 3 g m(-2) day 1 and vinorelbine 25 mg m(-2) day 1 and 8 every 21 days) and CaN (carboplatin 350 mg m(-2) day 1 and vinorelbine 25 mg m(-2) days 1 and 8 every 28 days). A total of 140 chemotherapy-naive patients entered the study; 49 patients were treated with MVP, 48 with PIN and 43 with CaN. Sixty-seven per cent of the patients had stage IV disease. Response rates, calculated on an 'intention to treat' basis, were as follows: MVP, 14.3% (95% CI 5.94-27.2%); PIN, 16.7% (95% CI 7.4-30.2%); and CaN, 14% (95% CI 5.3-27.9%). The overall median survivals were 256, 269 and 243 days for patients treated with MVP, PIN and CaN respectively. Myelosuppression was the most frequent toxicity: grade 3-4 leucopenia was observed in 14.3%, 25% and 18.6% of patients treated with MVP, PIN and CaN respectively. This multicentre phase II randomized trial shows that MVP, PIN and CaN can be administered on an outpatient basis with acceptable toxicities. Unfortunately, the three regimens showed an activity significantly lower than that reported in previous single-institution phase II trials.
Adult↗
Protein-bound male urinary pheromones: differential responses according to age and gender.
The attractive properties of male urinary pheromones were tested on adult or prepubertal male and female mice. An androgen-dependent protein is present in adult male urine (major urinary protein, MUP) which has been suggested to be a pheromone-binding protein. We tested the pheromonal properties of the protein-bound volatiles in a test of attractiveness. These molecules, that co-purify with MUP, attract females and repel adult males. In prepubertal animals, females are repelled and males are attracted by the same stimuli. These results are similar to those obtained by others with adult male whole urine. Therefore MUP binds molecules with a pheromonal activity, and these molecules are sufficient to act as male signals.
Age Factors↗
Outcome of laparoscopic transabdominal preperitoneal inguinal hernia repair.
The long-term efficacy of laparoscopic inguinal hernia repair is unknown. This retrospective study was conducted to determine the efficacy of this operation in comparison with the open technique and to evaluate the possible factors of recurrence. We have evaluated the clinical outcome in a group of patients who underwent laparoscopic procedures between January 1995 and December 1996, with the aim of assessing the incidence of recurrence and of long-term complications. Sixty-three patients underwent laparoscopic transabdominal preperitoneal repair by use of a large mesh. We were able to examine 58 of these patients at a median follow-up time of 15 months since their operation. Four patients had developed a recurrence, and two patients had significant symptoms consistent with nerve damage. The recurrence rate of 7% is similar to that reported for open operations but higher than that reported for early follow-up after laparoscopic operations. Our study illustrates the value of long-term follow-up for the assessment of efficacy following laparoscopic inguinal hernia surgery.
Adolescent↗
[Primary neuroendocrine tumor in the intrahepatic bile ducts: a rare finding in an asymptomatic patient].
Neuroendocrine tumors of the biliary tree are rare. In all cases except one, diagnosis was made in symptomatic patients. We report a case of an asymptomatic intrahepatic bile duct neuroendocrine tumor in a 74-year old man. To our knowledge, this is the second reported case of an asymptomatic intrahepatic bile duct neuroendocrine tumor. Diagnosis was only made by anatomopathological examination of the tumor after resection. Systemic and immunohistochemical hormonal screening was negative. Twenty months after surgery, the patient was asymptomatic and there was no recurrence.
Aged↗
Filgrastim and lack of support of intensive adjuvant chemotherapy for high-risk breast cancer patients.
The capacity of filgrastim to reduce the myelotoxicity of a 16-week intensive chemotherapy regimen has been investigated in 24 operable breast cancer patients with > or = 10 metastatic axillary nodes. Five patients were treated with chemotherapy alone (control group); 19 patients were treated with chemotherapy and filgrastim, 5 microg/kg/day s.c. Six patients in the latter group were treated from day 4 to day 7 (level 1), seven from day 10 to day 13 (level 2), and six from day 4 to day 7 and day 10 to day 13 (level 3). A total of 135 courses were administered: neutropenia was the most severe toxicity, and the prophylactic use of filgrastim does not reduce its severity. Moreover, the dose intensities of antiblastic drugs actually received by the patients were not significantly different in the four study groups. Among the patients treated at level 3, there were three toxic deaths: one patient died because of febrile neutropenia and sepsis, two patients because of ischemic colitis. At a median follow-up of 15 months, 17 patients were alive, and 15 patients were disease free. The use of filgrastim does not ameliorate myelotoxicity and does not allow the administration of the planned doses of antiblastic drugs of a 16-week intensive chemotherapy regimen.
Adult↗
Dose-finding study and pharmacokinetics of epirubicin and paclitaxel over 3 hours: a regimen with high activity and low cardiotoxicity in advanced breast cancer.
PURPOSE: To determine the maximum-tolerated dose (MTD) of paclitaxel over 3 hours with a fixed dose of epirubicin, to investigate the plasma pharmacokinetics of this combination, and to evaluate the toxicity and the activity in previously untreated metastatic breast cancer patients. PATIENTS AND METHODS: Fifty patients with metastatic breast cancer, measurable disease, and normal left ventricular ejection fraction (LVEF) were eligible. Epirubicin was administered as an intravenous (I.V.) bolus at the fixed dose of 90 mg/m2 before the infusion of paclitaxel over 3 hours. The initial dose of paclitaxel was 135 mg/m2 and was increased by 20 mg/m2 in subsequent cohorts of six patients until dose-limiting toxicity (DLT). Plasma pharmacokinetics of paclitaxel and epirubicin was performed at cycle 1 in at least two patients per dose level of paclitaxel (175 up to 225 mg/m2). RESULTS: The DLT of this combination was febrile neutropenia in two of eight patients who received paclitaxel at 225 mg/m2. The mean peak plasma concentration of paclitaxel ranged between 5.1 and 6.2 micromol/L at doses of 175 to 225 mg/m2. The concentration of epirubicinol decreased from 47.3 +/- 9.4 to 37.9 +/- 7.5 ng/mL in patients treated with paclitaxel 175 and 225 mg/m2. The most relevant toxicity was grade 4 neutropenia (61% of all courses). The pharmacokinetic data of paclitaxel, in particular the time above the threshold level of 0.05 micromol/L, were not significantly related to myelosuppression. Cardiac toxicity was mild: three patients (6%) developed mild congestive heart failure that was responsive to therapy. Among 49 assessable patients, 41 responses (84%; 95% confidence interval [CI], 70% to 92%) were observed, and nine (18%) of these were complete. CONCLUSION: Our study demonstrates that (1) the MTD is epirubicin 90 mg/m2 and paclitaxel 200 mg/m2; (2) no clear relationship exists between pharmacokinetic data of paclitaxel and myelosuppression, while the increase in the dose of paclitaxel is associated with a reduction in epirubicinol plasma levels; and (3) the association is feasible, with low cardiotoxicity, and has a high activity in metastatic breast cancer.
Adult↗
A rare laparoscopic diagnosis in acute abdominal pain: torsion of epiploic appendix.
Torsion of an epiploic appendix is seldom diagnosed preoperatively because of the difficult differential diagnosis with other diseases causing acute abdominal pain, particularly appendicitis. The classic McBurney approach overlooks many infarcted epiploic appendixes. The use of diagnostic laparoscopy in acute abdominal pain can show an infarcted epiploic appendix to be at the origin of pain. Four patients were admitted for acute abdominal pain and moderate tenderness in lower quadrants and were operated on for suspected acute appendicitis. In all cases laparoscopy found the torsion of an epiploic appendix, which was resected, and a normal cecal appendix. Postoperative course was uneventful. In case of acute abdominal pain in the lower quadrants of suspected appendiceal origin, laparoscopy should be routinely performed not only in women but also in men to avoid overlooking other intraperitoneal diseases that can be the cause of symptoms.
Abdomen, Acute↗
[Hepatic resection and transplantation for hepatocellular carcinoma in patients with cirrhosis].
OBJECTIVES: Liver resection and liver transplantation are the only curative treatments for hepatocellular carcinoma in patients with cirrhosis. The aim of this retrospective study was to compare survival and tumor recurrence in patients with cirrhosis after hepatic resection or liver transplantation for hepatocellular carcinoma in patients with cirrhosis. METHODS: Between March 1988 and March 1995, 34 patients underwent liver resection and 30 patients with cirrhosis had liver transplantation for hepatocellular carcinoma. The probability of survival and recurrence were studied according to clinical, biological and pathological factors, defined in liver specimens. Comparisons were performed by the actuarial method and log rank test. RESULTS: Five-year survival after resection and transplantation was 13% and 32.6%, respectively, and 5-year recurrence was 92.6% and 40.9%, respectively (P < 0.01). The diameter of nodules was a significant predictive factor of recurrence in resected patients; the number of nodules was a significant predictive factor in transplanted patients. The combination of these two factors could be used to identify two groups: patients with large carcinoma (diameter > 5 cm and/or number of nodules > 3), and patients with small carcinoma (diameter < or = 5 cm and number of nodules < or = 3). The five-year survival rate of large hepatocellular carcinoma was 17.3% after resection and 0% after transplantation. The five-year survival rate of small hepatocellular carcinoma was 0% after resection and 69.3% after transplantation (P < 0.01). The five-year recurrence of large hepatocellular carcinoma was 72.3% after resection and 100% after transplantation. The five-year recurrence of small hepatocellular carcinoma was 82.6% after resection and 11.1% after transplantation (P < 0.01). CONCLUSIONS: Liver transplantation seems to be the best treatment for small hepatocellular carcinoma, mainly because of a lower recurrence rate. On the other hand, both treatments had a high recurrence rate in large hepatocellular carcinoma.
Carcinoma, Hepatocellular↗
[Volvulus of the gallbladder: a difficult diagnosis requiring urgent operation].
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Aged↗
Effects of primary chemotherapy on biological parameters of locally advanced breast cancer.
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Adult↗
Chemotherapy with or without estrogenic recruitment in metastatic breast cancer. A randomized trial of the Gruppo Oncologico Nord Ovest (GONO).
BACKGROUND: This phase III study was carried out to verify whether a kinetic recruitment induced with low doses of diethylstilbestrol (DES) could increase the antitumor activity of chemotherapy in patients with advanced breast cancer. PATIENTS AND METHODS: Two hundred fifty-eight women with metastatic breast cancer were randomized to receive chemotherapy consisting of cyclophosphamide 600 mg/sqm i.v., epidoxorubicin 60 mg/sqm i.v. and fluorouracil 600 mg/ sqm i.v. (CEF) on day 1 or DES-CEF (diethylstilbestrol 1 mg orally days 1-3 CEF on day 4) every 21 days. Patients were treated until progression or, if responsive, for a maximum of 10 courses. RESULTS: There were no significant differences between the two treatment arms in response rates (51.3% to CEF and 49.6% for DES-CEF); median progression-free survival (9.4 months for CEF and 11 months for DES-CEF group) or median overall survival (17.3 and 20 months for CEF and DES-CEF arms, respectively). Non-hematological toxicities were superimposable in the two arms, while DES-chemotherapy was more myelotoxic. CONCLUSIONS: This trial confirms that chemotherapy preceded by estrogenic recruitment is still in an experimental phase and that, at present, it has no role in clinical practice. Further research is needed to test the possibility of combining different mitogens in the light of new information about breast cancer cell growth.
Adult↗
Phase II study of vinorelbine/ifosfamide/cisplatin for the treatment of advanced non-small-cell lung cancer.
PURPOSE: To evaluate the combination of vinorelbine, ifosfamide and cisplatin (VIP) in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Seventy-six untreated patients with stages IIIB-IV NSCLC; the chemotherapy regimen consisted of vinorelbine (25 mg/sqm on days 1 and 8), ifosfamide (3 g/sqm on day 1 with uroprotective mesna), and cisplatin (80 mg/sqm on day 1). The cycles were administered on an outpatient basis every 3 weeks. RESULTS: Leukopenia was the most frequent toxicity: grades 3-4 neutropenia was observed in 26% of the cycles and 19 episodes of febrile neutropenia were reported in 289 evaluable courses. Filgrastim 5 micrograms/kg was administered in 27% of the courses. Sixty-seven of 76 patients were evaluable for response: the overall response rate was 51% (95% confidence interval 35%-77%) with 2 complete responses (3%) and 32 (48%) partial responses. No significant differences in response rate were observed according to histology or stage of disease. The median time to progression was 6 months (range 1 to 29+) and the median overall survival 10 months (range 1-33+). CONCLUSION: The combination of vinorelbine, ifosfamide and cisplatin in the dose and schedule employed in this trial shows an interesting response rate with acceptable toxicities. This regimen should be tested in the multimodality therapy of stage IIIA/B NSCLC.
Adult↗
Paclitaxel and vinorelbine in anthracycline-pretreated breast cancer: a phase II study.
BACKGROUND: Paclitaxel and vinorelbine are active in advanced breast cancer pretreated with anthracyclines We therefore conducted a phase II study to define the toxicity and activity of paclitaxel and vinorelbine administered in combination. PATIENTS AND METHODS: Our patient population consisted of 37 patients with metastatic breast cancer, 35 of whom had received prior chemotherapy including anthracyclines. The treatment regimen included vinorelbine (25 mg/m2 i.v.) followed by paclitaxel (135 mg/m2 i.v. as a 3-hour infusion) on day 1; vinorelbine was repeated on day 8 in the first 14 patients and on day 3 in the remaining 23 patients. RESULTS: Because of grade 4 neutropenia, the second dose of vinorelbine was reduced or omitted in 88% of the courses on the days 1 and 8 schedule and in 48% of the courses on the days 1 and 3 schedule. As a consequence the administered dose intensity of vinorelbine was significantly higher on the days 1 and 3 schedule (13 mg/m2/wk versus 8.3 mg/m2/ wk, P = 0.005). The overall response rate was 38% (95% CI: 22-55); four responses have been observed in the ten patients with absolute anthracycline resistance. The median duration of response was 6.5 months. CONCLUSIONS: The combination of paclitaxel and vinorelbine is a feasible and active salvage regimen in advanced breast cancer patients pretreated with anthracyclines.
Adult↗
Phase II study of oral doxifluridine in elderly patients with advanced non-small-cell lung cancer.
Elderly patients with advanced non-small-cell lung cancer (NSCLC) are usually excluded from most clinical trials because of the toxicity associated with chemotherapy. About 50% of the new cases of lung cancer occur in patients older than 65 years. Doxifluridine is a fluoropyrimidine derivate which can be administered orally with very low toxicities. This phase II study evaluates the toxicity and activity of a home therapy with oral doxifluridine in elderly advanced NSCLC patients. Thirty-three advanced NSCLC patients, aged 70 years or more, entered the study; median ECOG performance status was 1 (0-2) and 22 patients (66.6%) had metastatic disease. Doxifluridine was given orally in three divided doses, for a total daily dose of 2,250 mg, for 4 consecutive days every week. The treatment was well tolerated; five patients (15%) experienced a grade 3 diarrhea which required doxifluridine dose reduction to 1,500 mg daily. Thirty-one patients are evaluable for response; four partial responses (12.9%) have been observed (95% confidence limit interval 3.6-29.8%); 17 patients (54.8%) had a stabilization of the disease. This study demonstrates that a home therapy with oral doxifluridine in elderly NSCLC patients is feasible and well tolerated and should encourage further studies.
Administration, Oral↗