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Biomedical subjects

V Lorusso

Publications and source records attributed to V Lorusso.

At least 91 records · Page 5Linked to original sources

CEOP-B alternated with VIMB in intermediate-grade and high-grade non-Hodgkin's lymphoma: a pilot study.

PURPOSE: To improve response and toxicity in treatment of non-Hodgkin's lymphomas (NHLs), a prospective single-arm trial was initiated using cyclophosphamide, epirubicin, vincristine, prednisone, and bleomycin (CEOP-B) alternated with etoposide (VP-16), ifosfamide, mitoxantrone, and bleomycin (VIMB). PATIENTS AND METHODS: From December 1988 to April 1992, 60 consecutive previously untreated patients with intermediate- or high-grade NHL were admitted to the study and were assessable. Patient characteristics were as follows: 32% greater than 60 years of age, 63% with stage III to IV disease, 42% with a performance status (PS) of 2 or 3, 23% with high lactate dehydrogenase (LDH) levels, and 22% with two or more extranodal disease sites. Stage I and II patients received three cycles of CEOP-B/VIMB plus radiotherapy (RT) to involved fields; stage III and IV patients received four cycles of chemotherapy alone. RESULTS: The complete remission (CR) rate was 77%; actuarial 48-month overall survival (OS) and time to treatment failure (TTF) rates were 70% and 59%, respectively. With univariate analysis, CR, OS, and TTF rates were significantly influenced by serum LDH levels (P = .0485, P = .0017, and P = .0064, respectively) and performance status (P = .0005, P < .00005, and P = .0001, respectively). The actuarial 48-month disease-free survival (DFS) rate was 83% and was negatively influenced only by high-grade histology (P < .004). Toxicity was mild. A lower epirubicin dose-intensity (DI) was found in patients older than 60 years of age, with a borderline P value. Patients were divided into four groups according to the International Prognostic Factor Project; low-risk and low-intermediate-risk groups had similar OS and TTF rates; when considered together, they showed superior, but not statistically significant, OS and TTF rates as compared with the high-intermediate-risk group, which in turn had significantly superior OS and TTF rates when compared with the high-risk group. CONCLUSION: CEOP-B/VIMB compares favorably with third-generation regimens and results in lower toxicity.

Actuarial Analysis↗

Solitary plasmacytoma of bone and extramedullary plasmacytoma: two different nosological entities?

BACKGROUND: The relationship between solitary plasmacytoma and multiple myeloma is still unclear, but they can be distinguished by their different clinical course. Indicators of disease activity and extension, and of a possible evolution to multiple myeloma, have not been identified as yet. METHODS: Two cases of solitary plasmacytoma are described: one of the mandible and one extramedullary plasmacytoma (EMP) of the rhinopharynx. Pathologic data included immunohistochemical staining for heavy and light Ig chains, and for the proliferating cell nuclear antigen (PCNA). Analysis of the peripheral immunological status and serum parameters (beta 2 microglobulin, thymidine kinase, IL-2, IL-6 and soluble IL-2 receptor) was performed and correlation was made with the clinical status. Flow cytometry analysis of nuclear DNA content and S-phase cell fraction were also studied in both neoplasms. RESULTS: Solitary plasmacytoma of bone (SPB) showed important basal immunologic alterations and a marked increase in all serum parameters considered with respect to EMP. Ploidy analysis demonstrated an almost complete aneuploidy cell population for the SPB patient (80%), whereas in the EMP patient only 2% of the cells were aneuploid. The S-phase cells were 16% and 4%, respectively. PCNA index was 60% in SPB and 10% in EMP. CONCLUSIONS: Solitary plasmacytoma of the bone appeared to be a more aggressive form of plasmacellular neoplasia, distinct from EMP and similar to multiple myeloma. The study of serum parameters, together with analysis of PCNA, ploidy and S-phase fraction, can aid in better understanding disease activity, and in the choice of more adequate treatment. Moreover, serial analysis of some serum factors might be useful markers for monitoring the disease.

Aged↗

High-performance liquid chromatographic assay of the magnetic resonance imaging contrast agent gadobenate in plasma, urine and bile.

Gadobenate dimeglumine (Gd-BOPTA-Dimeg) is currently under evaluation as an intravascular paramagnetic contrast agent for magnetic resonance imaging. The anion Gd-BOPTA2- is the moiety of Gd-BOPTA-Dimeg responsible for contrast enhancement. An HPLC method for assaying gadobenate (Gd-BOPTA2-) in plasma, urine and bile samples is described. The analysis is based on the reversed-phase chromatographic separation of the ion pair Gd-BOPTA(2-)-tetrabutylammonium from the endogenous components of biological fluids and its detection by UV absorption at 210 nm. The mean accuracy and precision of the method were in the range -3.4 to +5.0% and 0.2-3.5%, respectively. The method detection limits for Gd-BOPTA2- in plasma (0.8 ml), urine (0.2 ml) and bile (1.0 ml) were 1.1, 7.6 and 1.7 microM (corresponding to 0.73, 5.1 and 1.1 micrograms/ml), respectively.

Animals↗

Pharmacokinetics and tissue distribution of iomeprol in animals.

The pharmacokinetics of iomeprol, a new triiodinated nonionic radiographic contrast agent, has been studied in rats, rabbits and dogs. Following intravenous administration, iomeprol did not bind measurably to plasma proteins and was rapidly excreted in unchanged form, mostly through the kidneys. The compound was rapidly distributed to the plasma and thence to the extracellular spaces. Iomeprol did not accumulate in specific organs or tissues except for those involved in its elimination, i.e. the kidneys and the liver. However, 24 h after administration, less than 1% of the injected dose remained in the tissues. The overall profile was very similar to the published profiles of other radiographic contrast agents used in uroangiography.

Animals↗

Preclinical safety assessment of iomeprol for injection as contrast medium for myelography.

A series of pharmaco-toxicological investigations were carried out in animals in order to assess the neurotolerance of iomeprol, a new nonionic iodinated contrast medium. After intrathecal administration iomeprol was completely eliminated from the cerebrospinal fluid, rapidly cleared from the plasma and excreted unchanged through the kidneys. When administrated intrathecally, iomeprol did not significantly alter the behavioural functions or the physiological activities of the brain. Unlike other contrast media, iomeprol was devoid of any epileptogenic activity. The acute neurotoxicity of iomeprol was comparable with that of iopamidol, but less than that of iohexol, iotrolan and iodixanol. Iomeprol was well tolerated in both rats and dogs following weekly intrathecal administrations for four weeks of doses up to three times higher than those foreseen for clinical use. High neurotolerance in animals and favourable physico-chemical characteristics make iomeprol particularly suitable as a contrast medium for both myelography and cerebral ventriculography.

Animals↗

Mitoxantrone in the treatment of recurrent ascites of pretreated ovarian carcinoma.

In this study we treated 19 patients with relapsed ovarian cancer with malignant peritoneal effusion. All patients were previously treated with cisplatin-containing regimens. Intraperitoneal mitoxantrone was administered at a dosage of 20-30 mg/mq repeated every 28 days if ascites was still present. No patient was treated with systemic chemotherapy during the study. In 15 of 19 patients progressive ascites reduction was obtained. Moreover, in 4 of 15 responsive patients, a progressive reduction of the quantity of ascites was observed even though the abdominal masses demonstrated an increase in volume. Serum concentrations of Mitoxantrone (MXN) were determined, in ten patients, by high performance liquid chromatography with spectrophotometric detection, and low serum levels (1-30 ng/ml) with a maximum at the first or second hour were revealed. In conclusion, in patients with ovarian carcinoma and recurrent neoplastic ascites, palliative treatment with mitoxantrone was effective and well tolerated. The reduction of ascites and frequency of paracentesis represents a marked advantage for these patients and improves their quality of life.

Adult↗

Solid-phase extraction of fluoropyrimidine derivatives on a copper-modified strong cation exchanger: determination of doxifluridine, 5-fluorouracil and its main metabolites in serum by high-performance liquid chromatography with ultraviolet detection.

A copper-modified strong cation exchange stationary phase was used for the solid phase extraction of the antineoplastic drug doxifluridine (5'-deoxy-5-fluorouridine) and some of its main metabolites from human serum. Sorption of fluoropyrimidine derivatives due to complex formation with copper(II) was maximal at pH values around neutrality. Analytes were eluted by ligand exchange with ammonia. The average recoveries ranged from 70% to 108%. Reversed-phase chromatography with ultraviolet detection was used for the separation and quantitation of the analytes. The overall procedure has been applied to serum samples from patients receiving doxifluridine chemotherapy, and a pharmacokinetic profile has been derived.

Adsorption↗

M-VECA (methotrexate, vinblastine, epidoxorubicin and carboplatin) in the treatment of advanced urothelial carcinoma.

AIMS AND BACKGROUND: Urothelial cancer is a chemosensitive disease. However, cisplatin or anthracycline-containing regimens still provoke severe toxicity mainly due to reduced renal function and poor performance status (PS) of 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. METHODS: Twenty patients with advanced urothelial tract tumors were treated with a chemotherapeutic regimen composed of methotrexate (30 mg/mq iv on days 1, 15, 22), vinblastine (3 mg/m2 iv on days 2, 15, 22), epidoxorubicin (35 mg/m2 iv on day 2) and carboplatin (250 mg/m2 iv on day 2) every four weeks (M-VECA). All patients had bidimensionally measurable disease. RESULTS: Of the 18 evaluable patients, 3 (17%) obtained complete response and 7 (33%) obtained partial response (50% overall response). The median duration of response was 50 weeks (range, 28-88+). Grade III-IV toxicity (leukothrombocytopenia and mucositis) was observed in 20% of cases. Nevertheless, recovery was prompt in all but 2 patients with poor PS who died of nadir sepsis. CONCLUSIONS: M-VECA was an effective regimen for the treatment of patients with metastatic urothelial tumors and was safely employed in patients with a good PS. However, the possibility of substituting carboplatin for cisplatin as neoadjuvant therapy for less advanced stages needs further investigation in randomized studies.

Aged↗

Prospective randomised trial comparing fluorouracil versus doxifluridine for the treatment of advanced colorectal cancer.

Doxifluridine (dFUR) is a fluoropyrimidine derivative that has shown activity on a variety of solid tumours. The purpose of this study was to compare its therapeutic effect with a standard fluorouracil (FU) regimen in patients with locally advanced or metastatic colorectal cancer. 222 previously untreated patients were randomised to receive dFUR (4000 mg/m2) or FU (500 mg/m2) daily for 5 days every 28 days. The primary tumour originated in the colon in two-thirds of the cases in both groups; approximately 90% of patients had metastatic extension, and liver involvement was present in 69% of the patients in the dFUR and FU groups. A good performance status (ECOG 0-1) was recorded in 90% of cases in both arms. A median of five cycles was administered to the patients (range 1-12). Only one partial response among 110 patients in the FU arm and one complete response and five partial responses out of 112 evaluable patients in the dFUR group were observed. Time to progression was significantly longer in the dFUR group (P = 0.02); overall survival, while longer in the dFUR arm (48 weeks vs. 39 weeks), was not significantly so (P = 0.08). Toxicity was acceptable in both arms, although grade 3-4 neurological side-effects and leukopenia were more common after dFUR infusion. Despite the low response rate, our results indicate that dFUR may be a superior alternative to FU. The possibility of enhancing significantly the activity of dFUR with biochemical modulators should be further investigated.

Adult↗

Carboplatin plus ifosfamide as salvage treatment of epithelial ovarian cancer: a pilot study.

PURPOSE: This study aimed to evaluate the activity and toxicity of carboplatin (PPL) and ifosfamide (IFO) in patients with epithelial ovarian cancer previously treated with cisplatin (CDDP)-containing regimens. PATIENTS AND METHODS: From July 1989 to December 1991, 35 patients with epithelial ovarian cancer relapsed or refractory to CDDP as first-line chemotherapy were treated. PPL was administered at a dose of 300 mg/m2 intravenously (IV) on day 1 and IFO at a dose of 1,500 mg/m2 IV on days 1 to 3 every 3 to 4 weeks. Criteria for evaluating previous response to CDDP were strictly defined. RESULTS: The overall response rate was 43% (complete response [CR], 6%; partial response [PR], 37%) and the median duration of response was 7 months (range, 3 to 16). In potentially platinum-sensitive (PPS; relapsed) patients, the overall response rate was 56%. None of the primary platinum-resistant (PPR) patients obtained a clinical response to PPL plus IFO, whereas one of five secondary platinum-resistant (SPR) patients obtained a PR. The regimen was easily manageable. CONCLUSION: PPL plus IFO is useful and well-tolerated combination in salvage treatment of patients with advanced ovarian cancer. However, clear synergism between PPL and IFO that could overcome intrinsic or acquired CDDP resistance was not observed. The advantage of PPL plus IFO as compared with CDDP-containing regimens is represented by the increased tolerability and the reduced neurotoxicity, nephrotoxicity, and ototoxicity as compared with CDDP-containing regimens. It is essential that the patient population be defined according to their previous response to platinum therapy in trials involving second-line therapy of ovarian cancer.

Adult↗

Salvage treatment after r-interferon alpha-2a in advanced neuroendocrine tumors.

The use of inteferon (IFN) in neuroendocrine advanced tumors has achieved control of hormonal symptoms but low objective tumor response rate. In patients resistant to, or failing on, IFN a second line treatment may be required. Seventeen patients having received recombinant IFN alpha-2a as last treatment entered the study. There were 12 carcinoids, 3 medullary thyroid carcinomas, one Merkel cell carcinoma, and one neuroendocrine pancreatic tumor. Two different treatments were used: one radiometabolic therapy with metaiodobenzylguanidine (MIBG) in 3 patients with high MIGB uptake and one polychemotherapy regimen, including streptozotocin 500 mg/m2 intravenously days 1, 2, 3 and epirubicin 75 mg/m2 intravenously day 1, in the remaining 14 patients. Stable disease with relief of symptoms and tumor marker reduction was obtained in two patients receiving MIGB therapy, whereas the third patient had progressive disease. In the chemotherapy group only one partial response was obtained and neither tumor marker reduction nor subjective improvement were seen. Our second-line treatment was not especially effective but may be considered for rapidly progressive and/or symptomatic disease. The radiometabolic therapy appears promising in symptomatic patients with small tumor burden whereas our chemotherapy regimen appears ineffective.

3-Iodobenzylguanidine↗

Metastatic involvement of the stomach secondary to breast carcinoma. A case report.

The Authors describe a case of gastric metastases from breast cancer. The staging procedures in breast cancer do not usually include the endoscopic examination of the gastroenteric tract; nevertheless the complaint of persistent gastric disorders in patients affected by metastatic breast cancers must not be underestimated. In this case the finding of gastric neoplastic involvement led to effective treatment of the above mentioned disorders and consequently to an improvement in the patient's quality of life. Moreover, the evaluation of this clinical case shows that chemotherapeutic treatment of this metastatic localisation does not differ from that of metastases in other sites.

Bone Neoplasms↗

Krukenberg tumor. A report of six cases.

The Authors present six cases of ovarian neoplasm with histological characteristics of typical Krukenberg tumor. Usually, Krukenberg Tumor is bilateral and often secondary to gastrointestinal carcinomas. Secondary ovarian neoplasms often become evident a short time after the diagnosis of primary tumor. Moreover, the post ovulatory rearrangement of the ovarian surface could favour the metastatic spread of cancerous cells. In four cases TAG 72 serum levels were useful in the monitoring of relapsing disease.

Adenocarcinoma↗

Prognostic factors in epithelial ovarian cancer.

In the present study the Authors have statistically evaluated the influence of the main prognostic factors in 160 women affected by epithelial ovarian cancer. They were sequentially observed at Oncologic Institute of Bari, Italy from december 1981 to december 1989. The prognostic factors (age, stage, grading, histological type, performance status and residual disease), have been evaluated through an actuarial analysis of survival and compared with those reported by many authors in literature. Our data confirm the relevance, among all, of the grading, the clinical stage and residual disease as traditional parameters. Furthermore it is proposable the use of new prognostic factors such as nuclear ploidy and proliferative activity (S-phase, labeling index).

Adult↗

Total circulating B lymphocyte abnormalities in a primary cerebral localization of non-Hodgkin lymphoma: a case report.

The authors describe a case of primary central nervous system lymphoma in a 43-year-old male. Interest in this rare form of B-lymphocyte non-Hodgkin's lymphoma is due to its increasing incidence in the last decade, especially in immunodeficient patients. Extraneural involvement was excluded by staging examinations: bilateral bone marrow biopsy from the posterior iliac crest, bipedal lymphography, abdominal CT scan, skeletal, thoracic and gastrointestinal X-rays, spinal puncture, ORL and clinical examination. The peripheral immunologic state was particularly interesting: there was a substantial decrease in total circulating B-lymphocytes at diagnosis (4.4% = 80/mmc; nv 13 +/- 4% = 287 +/- 130/mmc) and a further decrease after 2 and 4 months of therapy (0.16% = 2/mmc). Three months after completion of therapy, the B-lymphocyte level returned to the base level at diagnosis (7% = 88/mmc). At 10 months after diagnosis and 3 months after completion of chemotherapy, the patient is alive and in good health except for the after-effects of a left hemiparesis. The etiologic and possible pathogenic factors are considered.

Adult↗

Measurement of the ovarian cancer-associated antigen CA 125 in monitoring tumor burden and response to chemotherapy.

CA 125 serum levels were measured in 74 patients with ovarian carcinoma. Among 31 patients undergoing a second look laparotomy (SL) after chemotherapy pathologic complete response (PCR) was observed in 14 patients, residual disease (RD) less than 2 cm in 7 patients and RD greater than 2 cm in 10 patients. The disease status was compared to the CA 125 serum levels measured just before SL. Thirteen of the 14 patients with PCR had serum CA 125 values less than 35 U/ml (specificity: 93%). On the other hand, only 10 of the 17 patients with RD showed serum levels greater than 35 U/ml (sensitivity: 59%). Moreover, in the 43 patients receiving chemotherapy, CA 125 levels correlated with the course of the disease in 36 (84%). With regard to early detection of recurrence, in 9/14 patients with PCR, whose CA 125 levels were monitored monthly, by 1 to 7 months an increase of the tumor marker preceded clinical evidence of relapse in 9/9 relapses (100%). In conclusion, CA 125 assay can be helpful in the management of ovarian cancer patients, in monitoring the response to chemotherapy, in the early detection of tumor recurrence, and in predicting the SL findings, although the low sensitivity could be a major drawback in patients with RD before SL.

Adult↗

Ifosfamide plus mitoxantrone as salvage treatment in non-Hodgkin's lymphomas.

Twenty-two patients affected by relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated with a combination of ifosfamide (IFO) at the dose of 1.2 g/m2 intravenous (i.v.) (1 h infusion) for 5 consecutive days with mesna as uroprotector plus mitoxantrone (NOV) at the dose of 12 mg/m2 i.v. on day 1; both drugs were recycled every 3-4 weeks. Of 21 evaluable patients, overall response observed was 57% (38% complete response and 19% partial response with a median duration of response of 7 months (5-23+). Dose-limiting toxicity was represented by leukopenia (grade III-IV in 43% of cases); severe thrombocytopenia was observed less frequently (grade III-IV in 19% of cases). This hematologic toxicity prevented administration of therapy every 3 weeks as initially planned. However, the complete hematological recovery, usually observed at the fourth week, permitted therapy administration to all patients without dose reduction. Low-grade lymphomas responded to treatment as well as intermediate or high grade lymphomas. Moreover, patients treated with third- or fourth-line chemotherapy also responded. However, response was observed in 11/13 (85%) relapsed patients as compared to 2/8 (25%) refractory cases. The combination of IFO plus NOV is active in heavily pretreated patients with NHL. Nevertheless, the study of a larger number of patients is necessary to better define the exact role of this combination as "salvage" therapy for NHL.

Adolescent↗

Tumor-proliferative activity, progesterone receptor status, estrogen receptor level, and clinical outcome of estrogen receptor-positive advanced breast cancer.

The relations among pretreatment tumor-proliferative activity, progesterone receptor (PgR) status, estrogen receptor (ER) level, and clinical outcome were analyzed in a series of 45 ER-positive advanced breast cancer postmenopausal women treated with tamoxifen (20 mg/day) until disease progression. Tritiated thymidine ([3H]dThd) Labeling Index (LI) by autoradiographic assay was utilized for proliferative activity analysis, whereas the dextran-coated charcoal method was used for ER and PgR evaluation (cutoff value, 10 fmol/mg of protein cytosol). The median [3H]dThd LI value was 1.8%; 73% of cases were PgR positive, and 53% were highly ER positive (greater than 100 fmol/mg of protein cytosol). Clinical responses were more frequently observed in slowly than in quickly proliferating tumors (86% versus 60%; P less than 0.05) but were similar for PgR-positive and -negative cases, as well as for those with high and low ER positivity. Only [3H]dThd LI was found to individualize patients with different survival rates (at 40 mo of follow-up, 78% versus 40% in slowly and quickly proliferating tumors, respectively). The [3H]dThd LI, monitored in ten patients by a second tumor biopsy after 14 days of tamoxifen therapy, was found to have a significantly lower median value (P = 0.03). These data indicate that pretreatment [3H]dThd LI provides information, which is not available in a study of PgR and ER status, on the clinical outcome of ER-positive advanced breast cancer patients treated by hormone therapy.

Breast Neoplasms↗