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Biomedical subjects

V Lorusso

Publications and source records attributed to V Lorusso.

At least 73 records · Page 4Linked to original sources
PubMed1999

The utility of a growth factor: r-HuEPO as a treatment for preoperative autologous blood donation in gynecological tumor surgery.

The use of r-HuEPO and sodium ferrous gluconate has been shown to be a safe and effective treatment which can be used by transfusional centers and surgeons to avoid allogeneic blood transfusions and to schedule short-term selective surgery. In this study the authors submitted 20 patients scheduled to undergo surgery for gynecological tumors to a program of pre-operative autologous blood donation. All the patients received both r-HuEPO and sodium ferrous gluconate in the pre- and post-donation period. r-HuEPO was administered subcutaneously in a dose of 200 IU/kg thrice weekly during the week before and after autologous blood donation (400 ml). Sodium ferrous gluconate was administered intravenously shortly before the first and fourth administration of 125 mg of r-HuEPO. Surgery was scheduled to be performed 10-15 days after the last r-HuEPo administration, i.e. within 15-20 days from blood donation. All the patients were tested for the following blood chemistry parameters: hematocrit, hemoglobin, sideremia and ferritin at treatment start, prior to donation, at treatment end, prior to autologous blood infusion and on the third and seventh day after surgery. No patient receiving r-HuEPO required allogeneic blood transfusion as both the hematocrit and hemoglobin values remained normal. r-HuEPO was observed to be a safe and effective treatment to be used in autologous blood donation programs in all patients scheduled to undergo surgery. It limits the decrease of hematocrit values following autologous blood donation thus enabling all the patients who for a variety of reasons to refuse allogeneic blood infusion to predeposit autologus blood shortly before the date scheduled for surgery.

Adult↗
PubMed1998

Combined carboplatin plus ifosfamide and cisplatin in patients with advanced ovarian carcinoma. A phase I-II study. GOCS (Gynecological Oncology Cooperative Study).

Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.

Adult↗
PubMed1998

A phase II study of gemcitabine in patients with transitional cell carcinoma of the urinary tract previously treated with platinum. Italian Co-operative Group on Bladder Cancer.

The aim of this study was to evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite, in the treatment of advanced transitional cell carcinoma of the urinary tract. 35 patients with unresectable or metastatic transitional cell carcinoma of the urinary tract previously treated with a platinum-based regimen were studied. Gemcitabine was administered at a dosage of 1200 mg/m2 as a 30-min intravenous infusion on days 1, 8 and 15, repeated every 28 days. 31 patients were evaluable for efficacy. 4 patients achieved a complete response (12.9%), 3 a partial response (9.6%) and 13 (42%) were stable for at least 4 weeks (overall response 22.5%; 95% confidence interval 8-37%). The median response duration was 11.8 months (range 3.6-17.7 + months) and median survival for all patients entered was 5 months (range 2-21 + months). 2 patients with complete response are still alive with no evidence of disease after 14 and 21 months. Gemcitabine also provided subjective symptomatic relief from pain, cystitis, dysuria, haematuria and peripheral oedema. Patients experienced little WHO grade 3-4 toxicity, with anaemia in 8 patients (23%), thrombocytopenia in 5 (14.2%), leucopenia in 4 (11.4%) and neutropenia in 7 (20%). WHO grade 3-4 hepatic toxicity occurred in 4 patients (11.4%) and transient elevations of transaminase was noted in 3 (8.6%). No patient had WHO grade 3-4 elevation of serum creatinine level. There was no WHO grade 4 symptomatic toxicity and no alopecia was noted. Transient influenza symptoms with gemcitabine occurred in 18 patients (51.4%) with 13 patients (37.1%) experiencing fever (2.9% WHO grade 3). In conclusion, gemcitabine is an new active agent for the treatment of transitional cell carcinoma of the urinary bladder with a mild toxicity profile; it warrants further investigation in combination with cisplatin in chemotherapy naive patients.

Adult↗
PubMed1998

Double modulation of 5-fluorouracil by methotrexate and high-dose L-leucovorin in advanced colorectal cancer.

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and L-leucovorin (L-LV) in patients with advanced recurrent (inoperable) or metastatic colorectal carcinoma (ACC). Between July 1993 and October 1995, 41 patients with ACC received a regimen that consisted of MTX 150 mg/m2 i.v., infused over a 20-minute period at hour 0, followed 19 hours later by L-LV 250 mg/m2 in a 2-hour i.v. infusion. 5-FU, 900 mg/m2, was administered by i.v. push injection at hour 20. Beginning 24 hours after MTX administration, all patients received four doses of L-LV, 15 mg/m2 i.m., every 6 hours. Cycles were repeated every 15 days. Two patients were not assessable for response. Objective regression was observed in 11 of 39 (28%) patients, [95% confidence interval (CI), 14-42%]. One (2%) patient achieved complete response (CR) and 10 (26%) partial response (PR). No change was recorded in 15 (39%) patients and progressive disease was noted in 13 (33%) patients. The median time to treatment failure was 6 months and the median survival time was 10 months. Toxicity was within acceptable limits, but one therapy-related death due to severe leukopenia was observed. The dose-limiting toxicity was mucositis. Eight episodes of grade 3 or 4 stomatitis were observed, and were responsible for dosage modifications of MTX and 5-FU. In conclusion, further in experimental and clinical studies are clearly necessary in order to design the best modulatory strategy of 5-FU.

Adult↗
PubMed1998

Neoadjuvant chemotherapy with accelerated CNF plus G-CSF in patients with breast cancer tumors larger than three centimeters: a pilot study.

From February 1992 to November 1993, forty patients with operable breast cancer tumors larger than three centimeters were enrolled in this study of accelerated neo-adjuvant chemotherapy. Thirty-seven patients are evaluable: one patient was excluded from the protocol and two refused to continue treatment after the first cycle. Chemotherapy consisted of three presurgical cycles of CNF [cyclophosphamide at 600 mg/m2, mitoxantrone (Novantrone) at 10 mg/m2 and 5-fluorouracil at 600 mg/m2] administered every 2 weeks, plus G-CSF (5 microg/kg s.c./day on days 7-12). Twenty-six of 37 patients (70%) achieved objective tumor response and were submitted to quadrantectomy. Toxicity was easily manageable. After a median 55-month follow-up (range 48-70), no locoregional recurrences were observed. Distant metastases occurred in 12/37 (32%) patients. The five-year disease-free (DFS) and overall (OS) survival were 58% and 80%, respectively. Accelerated CNF plus G-CSF proved to be a safe and tolerable regimen yielding a good clinical response thereby increasing the possibility of breast conservation surgery for patients otherwise candidates for mastectomy.

Adult↗
PubMed1998

Serological diagnosis of respiratory viral infections. A five-year study of hospitalised patients.

The results of a five-year study of paired sera from 410 hospitalised patients-mainly children-with respiratory illness are reported. Samples were divided into groups based on clinical diagnosis. The data of each group were analysed in relation to patient age (under or over 1 year of age). The percentage of positive serological diagnoses ranged from 29.4% in the respiratory viral illness group to 46.2% in the bronchiolitis group. Each group showed a prevalent serological diagnosis. Respiratory viral illness patients over 1 year were diagnosed mainly with Influenza virus infection (73.8% positive diagnosis), pharyngotonsillitis patients with Adenovirus infection (72.2%), laryngitis patients with Parainfluenza virus infection (100%), pneumonia patients with Mycoplasma pneumoniae infection (56.7%), and bronchiolitis patients with Respiratory Syncytial virus infection (100%). The serological diagnosis patterns of each group or subgroup were statistically significant with respect to the other groups (chi 2 or Fisher exact tests). Unlike previous reports, none of the patients under 1 year in our study was diagnosed with Influenza virus infection or Parainfluenza virus type 3. Conversely, Respiratory Syncytial virus infection data were in line with previous reports, being the most frequently diagnosed infection in the bronchiolitis group and in the subgroups of patients under 1 year of age. The present report provides new information on patterns of respiratory infections.

Adenoviridae↗
PubMed1997

Gadolinium chelates with weak binding to serum proteins. A new class of high-efficiency, general purpose contrast agents for magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The authors assess the effect of weak protein binding on the efficacy of gadolinium chelates as contrast agents for magnetic resonance imaging (MRI). METHODS: Chelates with no (gadopentetate dimeglumine), weak (gadobenate dimeglumine), and strong (B-21326/7) protein binding were compared by in vitro MRI at 2T (spin echo [SE]: repetition time [TR]/echo time [TE] 350/8 mseconds) on solutions in 0.5 mM bovine serum albumin and in rat whole blood, and by in vivo MRI at 2T on rat models of brain tumors (SE TR/TE 350/10 mseconds) and of focal blood-brain barrier disruption (SE TR/TE 400/15 mseconds) after injection of MPP+. Relaxation rate enhancement in the blood of normal rabbits was measured in vivo after administration of contrast agents using IR-Snapshot FLASH. RESULTS: Signal intensity enhancement measured in vitro for whole rat blood 0.1 mM in gadobenate was 142% relative to the same concentration of gadopentetate. Peak signal intensity enhancement in brain tumors was 87% +/- 8% and 64% +/- 5% after 0.1 mmol/kg intravenous administration of gadobenate and gadopentetate, respectively; in MPP+ lesions, the peak signal intensity enhancement was 22% +/- 9%, 32% +/- 7%, and 64% +/- 14% after 0.2 mmol/kg intravenous of gadopentetate, gadobenate, and B-21326/7, respectively. In rabbits, the relaxation enhancement of blood 5 minutes after B-21326/7 and gadobenate administration was 323% and 182%, respectively, relative to the same dose (0.1 mmol/kg intravenous) of gadopentetate. CONCLUSIONS: Weak protein binding can substantially increase the efficacy of gadolinium chelates as general purpose contrast agents for MRI.

Animals↗
PubMed1997

Revertant and potentiating activity of lonidamine in patients with ovarian cancer previously treated with platinum.

PURPOSE: Lonidamine (LND) is an energolytic derivative of indazol-carboxylic acid that has been shown to enhance cisplatin (CDDP) activity in both sensitive (A2780) and resistant (A2780/Cp8) ovarian cancer cell lines. The aim of this study was to confirm the potentiating or reverting activity of LND on CDDP activity obtained in experimental models in a phase II study of advanced ovarian cancer patients previously treated with platinum-based regimens. PATIENTS AND METHODS: Twenty-seven consecutive women with histologically proven and measurable ovarian cancer previously treated with platinum compounds were treated with CDDP plus LND. CDDP was administered at 1 mg/kg intravenously (IV) once weekly for 6 weeks and every 3 weeks thereafter until disease progression or toxicity. LND was administered at 450 mg daily (1 tablet every 8 hours) for the entire period of therapy starting 3 days before the first CDDP administration. In addition, a higher LND dosage was provided on the day of CDDP administration in an attempt to maximize the synergy of this drug with CDDP. RESULTS: Ten patients achieved a complete response (CR) or partial response (PR) for an overall response rate of 37% (95% confidence interval [CI], 19% to 55%). In particular, responses were observed in five of 18 (28%) refractory or early relapsed patients (one CR and four PRs) and in five of nine patients (55%) in the late-relapsed group (two CRs and three PRs). Grade 3 or 4 anemia, leukopenia, and thrombocytopenia were observed in 19%, 15%, and 11% of patients, respectively, whereas seven of 27 patients (26%) showed LND-related myalgia. Grade 3 renal toxicity was observed in two patients (8%). Neurotoxicity, often concealed by LND-related myalgia, was recorded as grade 1 or 2 in six patients (22%) and as grade 3 in one (4%). CONCLUSION: The 37% response rate observed in this study (28% in refractory or early-relapsed patients), suggests that the synergism between CDDP and LND observed in vitro against ovarian cancer cell lines can be clinically confirmed. However, larger series and randomized studies are needed to assess definitely the revertant activity of LND on CDDP-refractory patients.

Adult↗
PubMed1997

Hepatocyte-directed MR contrast agents. Can we take advantage of bile acids?

A series of gadolinium complexes conjugated to bile acids was prepared and investigated as possible hepatospecific MR imaging contrast agents. In the design of such compounds, features such as the nature of the bile acid, the site of conjugation on the bile acid skeleton, and the global charge of the conjugate were taken into account. Relaxivity measurements carried out in human serum indicate interaction of the conjugates with human serum proteins; even small structural variations significantly affect relaxivity in human serum. Pharmacokinetic data (biliary elimination in the range of 18.4-45.6%) show that bile acids can be used as address moieties to transport gadolinium complexes through hepatocytes. For a homogeneous series of compounds, differing only in the bile acid residue conjugated, it was unexpectedly found that cholic acid is twice as efficient an address moiety as cholylglycine or cholyltaurine. Preliminary results show that none of the conjugates is transported through the basolateral membrane of hepatocytes by the Na+/taurocholate carrier.

Animals↗
PubMed1996

Double biochemical modulation of 5-fluorouracil by methotrexate and levo-folinic acid in the treatment of advanced digestive tract malignancies.

The aim of this study was to evaluate the activity and toxicity of a double biochemical modulation of 5-fluorouracil (5-FU) by means of methotrexate (MTX) and levo-folinic acid (LFA) in patients with advanced carcinoma of the digestive tract, and to assess the prognostic significance of MTX serum concentrations achieved in these patients. 94 patients affected by advanced carcinoma of the colon-rectum, stomach or biliary tract (47 of them previously untreated) received a regimen consisting of MTX 500 mg/m2 as a 2-h i.v. infusion on day 1, followed by LFA 250 mg/m2 as a 2-h i.v. infusion and 5-FU 600 mg/m2 as an i.v. bolus on day 2. Cycles were repeated every 2 weeks. Treatment was administered until tumour progression or for a maximum of 24 courses. MTX serum level was assessed soon after and 24 h (24-h MTXs) after its infusion in 61 patients. One complete and 22 partial responses were obtained, giving an overall activity of 24% (95% confidence interval, 16-34%). Response rate was 30% in chemotherapy-naive patients (colorectal, 26%; gastric, 37%; and biliary-tract, 22%) and 19% in those previously treated (all with fluoropyrimidines). A poor performance status adversely affected the response and survival of patients. The toxicity of treatment was very mild, and occurrence of severe diarrhoea (11% of patients) and mucositis (3%) was lower than that reported with other modulations of 5-FU. A cut-off value of 24-h MTXs was identified as a strong prognostic indicator. Patients with 24-h MTXs > or = 2 microM had a significantly better probability of response (37% versus 5%; P = 0.032), longer progression-free survival (5.3 versus 2.3 months; P = 0.023) and overall survival (10.8 versus 8.3 months; P = 0.045) on multivariate analysis. In chemotherapy-naive colorectal cancer patients, those with 24-h MTXs > or = 2 microM had a response rate of 38% (3/8), with a 19.6-month median survival time, as compared to no responses (0/4) and a 9.9-month median survival in the group with a lower serum concentration. The achievement of such MTX serum levels yielded a 31% (4/13) response rate even in colorectal patients who had previously received a 5-FU-FA treatment.

Adenocarcinoma↗
PubMed1996

Treatment of advanced urothelial carcinoma with M-VECA (methotrexate, vinblastine, epirubicin and carboplatin).

Transitional cell carcinoma of the urinary tract is actually considered very sensitive to cisplatin-containing regimens. Nevertheless, the generally impaired renal function and poor performance status of these patients are responsible for the severe toxicity usually occurring when cisplatin, either alone or in combination with other agents, is administered to these patients. The aim of this study was to verify the possibility of substituting carboplatin for cisplatin, and epirubicin for doxorubicin in the M-VAC regimen in order to reduce toxicity and improve patient tolerance. Thirty-five patients with advanced urothelial tract carcinoma were treated with a chemotherapeutic regimen composed of methotrexate (30 mg/m2 iv on days 1, 15, 22), vinblastine (3 mg/m2 iv on days 2, 15, 22), epirubicin (35 mg/m2 iv on day 2) and carboplatin (250 mg/m2 iv on day 2) every 4 weeks (M-VECA). All patients had bidimensionally measurable disease. Of the 32 evaluable patients, 5 (16%) obtained a complete response and 10 (31%) a partial response (response rate: 47% C.I. = 30%-64%). Grade III-IV leuko-thrombocytopenia was observed in 25%, and mucositis in 19% of cases. Nevertheless, recovery was prompt and opportune dosage reductions avoided severe toxicity in subsequent cycles in most patients. In conclusion, M-VECA is a safe and effective regimen for the treatment of patients with metastatic urothelial tumors.

Adult↗
PubMed1995

An on-line semi-automated solid-phase extraction procedure for high-performance liquid chromatographic determination of lonidamine in serum.

A semi-automated solid-phase extraction procedure on-line with gradient elution reversed-phase chromatography permits the determination of lonidamine and its metabolite in human serum. The average recovery from serum at the 2.5 micrograms ml-1 level was (92.8 +/- 3.4)%. The limit of quantitation for a 100 microliter sample size was 50 ng ml-1. The within-day (n = 5) and between-day (n = 5) relative standard deviations for lonidamine determination in serum samples spiked at the 2.5 micrograms ml-1 level were 2.7% and 4.5%, respectively.

Antineoplastic Agents↗
PubMed1995

Hepatic transport of the magnetic resonance imaging contrast agent gadobenate dimeglumine in the rat.

RATIONALE AND OBJECTIVES: Gadobenate dimeglumine is a new octadentate gadolinium (III) complex salified with meglumine. The compound is currently under evaluation as an intravenously administered paramagnetic contrast agent for magnetic resonance (MR) imaging. We investigated the mechanisms involved in the biliary excretion of gadobenate ion, the contrast-effective ion in gadobenate dimeglumine. METHODS: Biliary and urinary excretion of gadobenate ion injected intravenously to rats at 0.25 mmol/kg was studied following pretreatment with bromosulfophthalein (BSP) disodium salt, sodium taurocholate (TC), or oxyphenonium bromide (OP) and at various times after common bile duct ligation. Gadobenate ion was assayed by high-pressure liquid chromatography in bile and urine. Plasma bilirubin levels after duct ligation were measured by colorimetric assay. RESULTS: The 90-min excretion of gadobenate ion into bile accounted for 35.5 +/- 3.7% and excretion into urine for 45.7 +/- 3.5% of the injected dose (mean +/- SD). Pretreatment with BSP reduced recovery of the compound in bile to less than 1% and increased urinary excretion to 65.6 +/- 4.7%. Gadobenate dimeglumine had a substantial choleretic effect that was completely abolished by pretreatment with BSP. Pretreatment with TC and OP did not change the biliary or urinary excretion of gadobenate ion. Surgical cholestasis led to a massive increase in plasma bilirubin levels from 3.9 +/- 2.2 (day of surgery) to 129 +/- 37 mumol/L (4 days after common bile duct ligature) and decreased 6-hr cumulative biliary excretion of gadobenate ion from 45 +/- 16% to 5.3 +/- 4.2% of the injected dose. Urinary excretion increased correspondingly from 49 +/- 15% to 83 +/- 12%. CONCLUSION: The transport of gadobenate ion from plasma to bile occurs in the rat mainly through the BSP/bilirubin transport systems.

Analysis of Variance↗
PubMed1995

Long-term subcutaneous recombinant interleukin-2 as maintenance therapy: biological effects and clinical implications.

Several trials have evaluated the therapeutic efficacy of rIL-2 combined with more traditional treatments such as chemotherapy and radiotherapy, but the use of IL-2 as adjuvant therapy for minimal residual disease or to maintain clinical response obtained with other standard treatments has yet to be investigated. The aim of the present trial was to study the biological effects of maintenance long-term treatment (6 months) with subcutaneous low-dose IL-2 in 16 patients with different neoplasms previously treated with chemo-immuno therapeutic regimens or with surgery (7 metastatic renal cancers, 5 locally advanced renal cancers previously subjected to radical nephrectomy, 2 metastatic breast cancers, 1 small cell lung cancer, and 1 metastatic melanoma). Clinical tolerability, feasibility and therapeutic implications are also discussed. The IL-2 schedule was as follows: 4.5 million IU/day, 3 times weekly for 6 months. A total of 14 patients completed therapy without requiring dose modifications and are free of progression after a median duration of 8+ months (range: 7+ to 34+) while two patients progressed during therapy (one inflammatory breast cancer and one renal cancer). Important and persistent hemato-immunostimulating effects in both soluble (IL-2, sIL-2R, IL-6) and cellular (lymphocyte subsets, monocytes, eosinophils) parameters were noted during the entire treatment. The IL-2 related toxicity was quite low. Moreover, this long-term IL-2 therapy could control neoplastic growth and thus prolong clinical response obtained with standard treatments. Prospective randomized studies regarding the clinical efficacy have been initiated.

Aged↗