Biomedical subjects

R Rosso

Publications and source records attributed to R Rosso.

464 records · Page 26Linked to original sources

PubMedDate not supplied

Treatment of metastatic colorectal carcinoma with lymphoblastoid interferon and 5-fluorouracil: data of a phase II study.

Many clinical trials have tested the combination of 5-fluorouracil and recombinant alpha-interferons in metastatic colorectal carcinoma. The efficacy of 5-fluorouracil and lymphoblastoid interferon was evaluated in a phase II study in which 31 patients with advanced colorectal carcinoma were enrolled. 5-Fluorouracil was administered at the dose of 600 mg/sqm bolus weekly and lymphoblastoid interferon was given intramuscularly at 3 million units every two days. All patients were evaluable for toxicity. Thirty patients were available for response: no complete response was recorded, three patients reached a partial response (10%), three a minor response (10%) and 18 progressed (59.4%). Overall median survival was 8 months. No grade IV toxicity was observed: in 2 patients grade III occurred and in 8 patients grade III fever and fatigue attributable to interferon developed. It appears that this combination does not yield better results than 5-fluorouracil alone.

Adult↗

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Heterogeneity of the alpha-interferon-mediated overexpression of class-I and class-II major histocompatibility complex molecules in primary cultured cancer cells.

Human alpha- and gamma-interferons (IFNs) have the capability of enhancing the expression of major histocompatibility complex-class I and class II (MHC-I and MHC-II) as well as other surface tumor associated antigens (TAA) on cancer cell lines. This capability, associated to the anti-proliferative effect observed both in vitro and in vivo, was the basis of the extended use of IFN in cancer patients. Despite the great expectations, several solid neoplasms resulted resistant to treatment with IFNs. In order to analyze the actual effects of IFNs on cancer, we treated primary cultures of different histotypes of cancer cell, which are well known to differ significantly from established cell lines, with escalating doses of alpha-IFN. In this paper, we demonstrate that a variable proportion of culture was able to potentiate the expression of MCH-I and MCH-II molecules on the surface. This finding suggests that a clear functional heterogeneity was present in primary cultures of cancer cells, that strictly reflected the in vivo situation. In addition, it is of note that in some histotypes, "natural" lymphoblastoid alpha-IFN was more effective than recombinant human alpha-IFN in the induction of this capability.

Histocompatibility Antigens Class I↗

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Suramin and serum insulin-like growth factor levels in metastatic cancer patients.

Suramin, a polysulphonated naphthylurea, inhibits the activity of several growth factors in in vitro experiments and clinical responses have been reported in human solid tumors. We decided to investigate the relationship between suramin treatment and serum levels of insulin-like growth factor I (IGF-I) and II (IGF-II) in advanced breast, prostate and lung cancer patients. The serum IGF-I, IGF-II levels were determined by radioimmunoassay. A significant decline of IGF-I and IGF-II serum levels was demonstrated in suramin treated patients. Our results suggest that suramin-induced IGF suppression could be one of the possible mechanisms of suramin action.

Aged↗

PubMedDate not supplied

[Tropisetron versus ondansetron in the prevention and control of emesis in patients undergoing chemotherapy with FAC/FEC for metastatic or surgically treated breast carcinoma].

UNLABELLED: OBJECTIVE. To compare the efficacy and tolerability of standard dosage of tropisetron and ondansetron in controlling emesis induced by chemotherapeutic regimen not containing cisplatin. DESIGN. Open, comparative, parallel-group, randomized study. SETTING. Day hospital to which patients were admitted only on the day on chemotherapy when the antiemetic was given intravenously. PATIENTS: Forty adult women with metastatic or operated breast cancer who could benefit by adjuvant treatment. EXCLUSION CRITERIA: pregnancy, breast-feeding, symptoms of intracranial hypertension, current medical conditions which could put the patient at risk (e.g. severe cardiac insufficiency, uncontrolled infection, etc.), abnormal bowel rhythm, and treatment with antitumoral drugs in the previous 6 months. TREATMENT. During three cycles of chemotherapy with FAC/FEC (600 mg/m2 5-fluro-uracil, 600 mg/m2 cyclophosphamide and 50 mg/m2 adriamycin or 60 mg/m2 epidoxorubicin) antiemetic treatment was given as follows: tropisetron 5 mg/day (in intravenous infusion before chemotherapy and then orally for 4 days) or ondansetron 8 mg x 3/day (the first dose intravenously before chemotherapy and the subsequent doses orally until the end of the fourth day after chemotherapy). OUTCOME MEASURES: Severity of nausea and number of vomiting episodes each day during antiemetic treatment; ECG; vital signs and blood tests before each cycle and at the end of the study; side effects. RESULTS: On the worst day of the three cycles complete control of emesis was obtained in 50, 75 and 84.6% of the patients treated with tropisetron and in 60, 58.8 and 66.7% of those who received ondansetron, the differences being not significant (p > 0.05). The only side effects were headache (in 1 patient given tropisetron) and skin rash (1 given ondansetron). CONCLUSIONS: The efficacy and tolerability of 5 mg/day of tropisetron and 24 mg/day of ondansetron were almost identical.

Adult↗

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Intraperitoneal infusion of recombinant human tumor necrosis factor and mitoxantrone in neoplastic ascites: a feasibility study.

In cancers limited to the abdominal cavity the intraperitoneal administration of antineoplastic drugs could be the treatment of choice because of both the limited systemic toxicity and the pharmacokinetic advantage. Preclinical studies suggest that the combination of Tumor Necrosis Factor (TNF) and mitoxantrone have a synergistic effect. On this basis, we conducted a study to verify the feasibility of the intraperitoneal administration of these drugs in patients with malignant ascites. Cohorts of three patients were treated with a fixed dose of mitoxantrone (6 mg/m2) and escalating doses of TNF (from 60 up to 200 mcg/m2), intraperitoneally, given for two hours once a week for at least four weeks. Seventeen patients with malignant ascites entered into the study. All but two patients received the planned four cycles. Sixty-six cycles were given. The most common side effects were fever (21-44% of cycles), chills (8-44%), fatigue (19-33%), loss of appetite (17-57%), malaise (25-43%), myalgia (33%), pain injection (25-83%), nausea/vomiting (33-64%). Severe fatigue, malaise and anorexia were observed only at doses of 200 mcg/m2 of TNF. Weekly intraperitoneal administration of mitoxantrone (6 mg/m2) and TNF (200 mcg/m2) is a feasible regimen with acceptable toxicity. The activity of this combination should be studied in properly designed phase II trials.

Aged↗

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Mitoxantrone in elderly women with advanced breast cancer: a phase II study.

Comorbidity has important implications in older breast cancer patients. Whether elderly patients are more likely to have a decreased tolerance to antineoplastic agents is still a question of debate. Chemotherapy-naive women with metastatic or locally advanced breast cancer aged > or = 68 years entered a phase II trial of Mitoxantrone given day 1 q 21 days. The dose of the drug was dependent on performance status (PS) and number of "minor" comorbid conditions: patients with ECOG PS = 2 and/or > or = 2 comorbid conditions received 10 mg/m2 and those with PS < 2 and < 2 comorbid conditions received 14 mg/m2. Twenty-seven patients, median age 77 years (range 68-86), received a median number of 5 courses (range 1-9). All 27 patients were evaluable for toxicity and 23 cases (patients receiving at least 3 courses) were evaluable for response. Partial response was observed in 6/23 cases (26%) and median duration of response was 6 months (range 3-9). Median overall survival was 8 months (range 2-34). Among cases receiving 10 mg/m2, 4 PR, 4 SD and 2 P were observed and in cases treated with 14 mg/m2, 2 PR, 5 SD and 6 P occurred. Treatment was well tolerated and no grade 4 toxicity was encountered. Mitoxantrone is an effective and well-tolerated regimen in elderly breast cancer patients presenting with comorbid conditions.

Aged↗

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Efficacy of the association of 13-cis-retinoic acid (13cRA) and alpha-interferon 2a (alpha-IFN 2a) in moderate-severe cervical intraepithelial neoplasia (CIN II-III): a pilot study.

Recent in vitro studies have suggested a possible therapeutic synergism between alpha-IFN 2a and 13cRA in certain neoplasias, while encouraging in vivo findings strongly support the enhanced effectiveness of the two agents when used in combination. The specific aim of our study was to evaluate the efficacy and the toxicity of the association of 13cRA and alpha-IFN 2a in patients with CIN II and CIN III who refused surgical treatment. Twenty-one patients (aged between 25 and 58 years), of which 14 were CIN II and 7 CIN III, entered the study. 13cRA (orally at 0.5-1 mg/Kg/day) and alpha-IFN 2a (intramuscular at 3x10(6) I.U./day for the first 15 days, then 3 times/week for the following four weeks) were administered simultaneously for eight consecutive weeks. 13/21 (62%) histologically verified objective responses (6 complete and 7 partial) were achieved. We also obtained 8 stable diseases. Compliance was generally good and no delays in therapy due to toxicity were recorded (except for two patients presenting WHO degree III cutaneous and mucosal toxicity which regressed one week after suspending treatment). Human Papilloma Virus (HPV) was initially detected in 16/21 (76%) patients, while HPV negativization after treatment was observed in 3/16 (19%). Although preliminary and requiring long-term assessment, the encouraging results of this study confirm the need for further investigation on the role of systemic medical therapy in the treatment of CINs.

Adult↗

PubMedDate not supplied

Splenic marginal zone cell lymphoma involving liver and bone marrow. Report of a case with protracted follow-up, showing progressive disappearance of the lymphoma after splenectomy.

We report the case of a 42-year-old man who presented with B-symptoms, moderate splenomegaly and multiple nodules in the liver. Histologically, lymphocytic infiltrates were seen in the portal spaces and sinusoids of the liver and in the paratrabecular areas of the bone marrow. After excision, the spleen showed minimal disturbance of architecture with an expansion of the follicular marginal zones. These findings were considered inconclusive for lymphoma and the patient was treated only with non-steroidal anti-inflammatory drugs for persisting fever. Five months after splenectomy, a bone marrow biopsy still showed diffuse lymphoid infiltrates. From then on, the patient's condition improved with no further evidence of disease. Ten years after splenectomy the case was reconsidered as a splenic marginal cell lymphoma, indolent variant. Immunohistochemical and gene rearrangement studies demonstrated the monoclonality of the splenic proliferation, supporting the diagnosis. A further bone marrow biopsy did not detect residual lymphoid infiltrates. This case confirms that splenic marginal zone cell lymphoma may have a deceptively favorable course, even when presenting at an advanced stage. Moreover, it indicates that extrasplenic localizations of the lymphoma may persist for a long while after splenectomy but may vanish over time without therapy.

Adult↗

PubMedDate not supplied

[Mobilization of peripheral blood stem cells with conventional chemotherapy].

Autologous peripheral blood progenitor cells (PBPC) rescue after high-dose chemotherapy has been used progressively as a form of treatment in some solid and hematologic tumors. This increasing use can be explained by both advantages of PBPC rescue over bone marrow rescue (decrease in the duration of marrow aplasia, reduction of platelet transfusions, earlier discharge from hospital, potential use in patients with inadequate bone marrow reserve) and the low number of aphereses (one or two) needed to collect a sufficient number of progenitor cells for autografting. High-dose chemotherapy is likely to be increasingly used after the results of two recently reported studies in which treatment with high-dose compared with standard-dose chemotherapy increases overall survival in metastatic breast cancer patients and relapsed lymphoma patients. After the initial use of unselected mobilizing regimens regardless of the patient characteristics and the tumor type, now it seems more useful to optimize this approach. Mobilization of PBPC can be obtained by several approaches. Moderate or high doses of single agent alone (e.g. cyclophosphamide 4-7 g/m2) or some hematopoietic growth factors alone (e.g. G-CSF, GM-CSF) have been proven to be adequate mobilizing agents. However, the use of hematopoietic growth factors alone may disadvantageously delay the start of an effective chemotherapy. An efficient mobilizing regimen requires the use of both chemotherapy and hematopoietic growth factors: the efficiency of mobilization was greater and with less side effects than chemotherapy alone. It was postulated that PBPC mobilization could be achieved only at hematopoietic recovery following myeloablative chemotherapy. Recently, it has been demonstrated that some standard-dose chemotherapy regimens associated with hematopoietic growth factors are efficient priming agents. We reported that standard-dose CEF chemotherapy plus filgrastim is a disease specific regimen (breast cancer) allowing PBPC mobilization without any relevant toxicity. The maximum release of PBPC has been observed at day 11. The optimal time for PBPC collection is predictable and aphereses can be guided by WBC counts. In conclusion, both standard and high dose chemotherapy are effective priming regimens. So presently a mobilizing regimen should be an effective disease specific chemotherapy program and should contain a hematopoletic growth factor. The choice between standard and high-dose chemotherapy can be based on patients characteristic and disease status.

Antineoplastic Agents↗

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Vinorelbine as palliative therapy in advanced breast cancer.

Thirty advanced breast cancer patients received Vinorelbine (VNB) according to two different schedules: a weekly i.v. bolus of 30 mg/m (14 patients) or a continuous infusion (CI) schedule comprising 8 mg i.v. bolus on day 1 followed by 8 mg/m2/die CI day 1 to 4, q 21 days (16 patients). 36% of patients had received at least two prior chemotherapy regimens for advanced disease and 57% had been treated with anthracycline-based palliative therapy. The overall response rate (CR + PR) was 33% (soft tissue 57%, bone 17%, viscera 29%). The main toxicities were neutropenia and abdominal pain. Vinorelbine is effective in pretreated advanced breast cancer patients.

Adult↗

PubMedDate not supplied

[Use of erythropoietin in oncology].

UNLABELLED: Anemia is a common complication observed in cancer patients. Its etiology is multifactorial and its severity depends on patient characteristics, type and stage of neoplasia, type of used chemotherapy. Erythropoietin can be effective by counteracting two of the main causes of anemia in cancer patients undergoing chemotherapy: 1. Myelosuppression induced by chemotherapy. Almost all cytotoxic drugs induce this effect. In this circumstance erythropoietin can be effective by accelerating the recovery of the erythroid compartment spared by chemotherapy. For this effect, higher than physiologically normal levels of erythropoietin are required. 2. Endogenous erythropoietin deficiency secondary to renal impairment. Renal impairment is primarily induced by cisplatin and leads to a deficient renal production of erythropoietin. In this case, erythropoietin administration can be considered as a hormone replacement therapy. Possible indications for the use of erythropoietin in cancer patients are the following: 1. Prevention of anemia; 2. Treatment of anemia induced by either high dose chemotherapy and bone marrow transplantation (BMT) or standard dose chemotherapy. The preventive use of erythropoietin is still under investigation. Two randomized studies reported the erythropoietin ability to prevent the anemia development. Further trials are required to identify subsets of patients in which the preventive use of the drug could be cost-effective. One of the causes of anemia after allogeneic BMT is the endogenous production of erythropoietin inappropriately low for the degree of anemia. On the contrary, after autologous BMT the erythropoietin response to anemia is appropriate. Phase III randomized studies showed the efficacy of erythropoietin in the treatment of anemia after allogeneic but not after autologous BMT. After standard dose chemotherapy, phase III randomized studies showed that erythropoietin is able to correct anemia in 60-80% of patients receiving platinum-based chemotherapy and in nearly 40% of patients receiving chemotherapy without platinum. The correction of anemia leads to a significant reduction in transfusion requirement. In solid tumors erythropoietin is commonly administered at the schedule of 150 U/Kg subcutaneously three times per week. Normal levels of current iron supply should be guaranteed by oral iron support during erythropoietin treatment. Because the response to erythropoietin occurs after a median time of 5 weeks, it is necessary to start erythropoietin therapy at an hemoglobin level higher that that triggering transfusion. Various parameters, at baseline or after 2-4 weeks of erythropoietin therapy, have been evaluated as predictors of response. However, other parameters should be studied to identify stronger predictors. CONCLUSIONS: Erythropoietin treatment is recommended after allogeneic BMT. Erythropoietin is effective in 60-80% of anemic patients receiving platinum-containing chemotherapy and in approximately 40% of patients receiving chemotherapy without platinum. The preventive use of erythropoietin is still under investigation. Further studies should identify subsets of patients and types of chemotherapy in which the prevention of anemia could be cost/effective.

Anemia↗

PubMedDate not supplied

Activity of high dose 24 hour 5-fluorouracil infusion plus L-leucovorin in advanced colorectal cancer.

BACKGROUND: Modulation of 5-fluorouracil (5-FU) by leucovorin (L-LV) in patients (pts) with advanced colorectal cancer has been demonstrated to produce a highly significant benefit over single-agent 5-FU in terms of tumor response rate, but this advantage does not translate into an evident improvement of overall survival. To improve the clinical efficacy of the 5-FU plus L-LV regimen a phase II study of weekly 24-hour high-dose 5-FU infusion with L-LV was undertaken. PATIENTS AND METHODS: Seventy advanced colorectal patients were enrolled and treated by a weekly outpatient combination regimen according to the following schedule: L-LV 100 mg/sqm by 4 hours i.v. infusion followed by 5-FU 2600 mg/sqm over a 24 hours infusion combined with a fixed dose of oral L-LV (50 mg) every 4 hours for 5 times. Forty-four pts did not receive any previous CT and 26 pts were pretreated with fluoropyrimidines. RESULTS: The overall objective response rate (OR) was 35.3%; 7 CR and 11 PR (42.8% OR) were observed in the group of untreated pts, and 6 PR (23% OR) were reported among previously treated pts. Major side effects were represented by diarrhoea (grade III: 26%, grade IV: 1%), hand-foot syndrome (grade III: 4%, grade IV: 1%) and mucositis (grade III: 4%); however, this did not significantly influence the therapeutic programme. Median 5-FU dose intensity was 100% and 80% at 4 weeks, 87% and 75% at 8 weeks in untreated and pretreated pts, respectively. CONCLUSIONS: L-Leucovorin modulation of weekly short-term continuous infusion of high-dose 5-fluorouracil appeared a well-tolerated outpatient regimen; it demonstrated a high activity in advanced colorectal cancer, both in untreated pts and in pts resistant to 5-FU-based chemotherapy.

Adult↗

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Hydration regimen and hematological toxicity of a cisplatin-based chemotherapy regimen. Clinical observations and pharmacokinetic analysis.

The administration of 100 mg/m2 Cisplatin (CDDP) in five 20 mg/m2 daily infusions together with bolus 5-Fluorouracil (5FU) allows patients with advanced head and neck cancer (HNC) to be treated with a rapidly alternating chemoradiotherapy regimen in an out-patient setting. Due to the extremely low rate of acute renal failure, the induction of forced diuresis is not mandatory, although hydration is usually performed at every CDDP administration. In this retrospective analysis of 73 homogenously treated HNC patients, the influence of hydration on hematological toxicity was studied. A lower incidence of grade II to IV acute myelosuppression (57% vs 92%; p < 0.005), together with a lower rate of anemia lasting two weeks or more (13% vs 46%; p < 0.009), were seen in the group of patients treated with CDDP along with a forced hydration scheme (2000 ml normal saline and 20 mg furosemide before the CDDP infusion) when compared to patients on a non-forced diuresis regimen (no furosemide and 1500 ml normal saline). The lower hematological toxicity translated into a better compliance to treatment. No differences in terms of other toxicities or response rate were evident between the two groups. A pharmacokinetic study with a cross over design was performed on 7 patients, and suggests that the first day Pt kinetics are not affected by the hydration scheme used, although a significantly lower Pt urinary concentration was found in the forced diuresis group. A further kinetic analysis performed on one additional patient over the entire five-day period of two consecutive cycles showed a marked increase in the AUC of filterable Pt and in the unbound Pt fraction (fu) from the second to the fifth day in the forced hydration course, while this was not the case in the non-forced hydration course. Results from this kinetic study support the hypothesis of a lowering of Pt reactive species after repeated CDDP-furosemide treatments and an influence of furosemide-induced diuresis on Pt binding to plasma proteins.

Adult↗

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[The perforation complication in diverticulitis: the evolution of the surgical procedure].

The ideal treatment for perforative complication in diverticular disease of the colon is still now rather controversial. Fundamental remains the simple and practical classification of Hinchey for perforated diverticulitis, especially for a meaningful evaluation of different experience. Without a common reference classification the percentage differences in mortality are completely devoid of scientific value. From a "three-stage" procedure the preferences are shifted towards a "two-stage procedure", thanks to the improvement of anesthetic and surgical modern facilities. The Hartmann procedure, performed not earlier than 4-6 months is the experience of the authors, but the ultimate choice is conditioned by the degree of peritoneal contamination.

Adult↗