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Biomedical subjects

A Vigani

Publications and source records attributed to A Vigani.

31 records · Page 2Linked to original sources
PubMed1990

Effect of recombinant human TNF on human ovarian cancer cell lines.

Ovarian cancer is the second most common gynecologic malignancy. Standard therapeutic approaches to this disease, surgery followed by chemotherapy, have produced response rates of up to 80%. However, the five-year survival rate remains around 30%. Recently, Tumor Necrosis Factor (TNF) has received attention as either an alternative or an associated agent for chemotherapy of ovarian cancer. TNF is known to have direct cytotoxic and cytostatic effects on a variety of transformed cell lines "in vitro". Furthermore, TNF is known to enhance significantly the "in vitro" effects of a class of chemotherapeutic agents, specifically those targeted at DNA topoisomerase II. In this work we have investigated TNF-induced cytotoxicity in four established human epithelial ovarian cancer cell lines: A-2774; SV-626; SKOV-3 and Pa-1. TNF mediated cytotoxic activity was observed in a range of concentrations between 1 U/ml and 10-3 U/ml. A-2774 and SV-626 were the two most sensitive lines, especially when exposed to high concentrations of TNF.

Cell Survival↗
PubMed1989

[Duodenopancreatectomy with conservation of the pylorus].

The authors report on their initial experience with pylorus-preserving pancreatoduodenectomy. In the last three years 11 patients with neoplastic disease of the pancreatic head and ampullary region underwent the above mentioned procedure. The surgical technique carefully preserved the blood supply and innervation to the antro-pyloric region and duodenum was transected 2 cm distal to the pylorus. Postoperative mortality was 9%. Postoperative nasogastric suction was required for eight days (median). Long term results are quite good with a satisfactory restoration of intestinal function and a weight gain of 95% of pre-illness weight. At the present time preserving the pylorus appears an usefull modification of Whipple procedure.

Adenocarcinoma↗
PubMedDate not supplied

Carboplatin and etoposide as outpatient treatment of advanced non-small-cell lung cancer.

Twenty-four outpatients with locally advanced (inoperable or unsuitable for radical radiotherapy) or metastatic non-small-cell lung cancer were treated with carboplatin (300 mg/m2 day 1)+etoposide (120 mg/2 day 1-3), every 3 weeks. Two patients died of disease progression before completing at least 2 cycles of chemotherapy. Four patients (16.7%) obtained a partial response, 10 had disease stabilization (41.7%) and 8 progressed (33.3%). Median overall survival was 8 months (range 1-22). Toxicity was moderate, with no nephro-, neuro- or ototoxicity.

Aged↗
PubMedDate not supplied

Sequential high dose-density chemotherapy with two active regimens for advanced small cell lung cancer.

16 patients with advanced small cell lung cancer were treated with a combination of cyclophosphamide (1000 mg/m2 day 1), epidoxorubicin (60 mg/m2 day 1) and vincristine (1.4 mg/m2 day 1) every 14 days for six cycles followed by a combination of cisplatin (40 mg/m2 days 1 & 2) and etoposide (100 mg/m2 days 1-3) every 14 days for four cycles. Shortening of intervals was obtained with the prophylactic employment of granulocyte colony-stimulating factor (filgrastim, 300 mcg subcutaneously from day 5 to dsy 10). In 11 patients ratio between actually delivered dose intensity and planned dose intensity of > 80% was obtained. Toxicity was acceptable and no life-threatening toxicities were observed. An objective response (partial or complete) was observed in 11 patients. The new regimen, incorporating the concepts of dose-intensification and sequential administration of regimens, is feasible and may be considered for further studies.

Aged↗
PubMedDate not supplied

Radiotherapy plus carboplatin and teniposide in patients with brain metastases from non small cell lung cancer.

BACKGROUND: The role of chemotherapy alone or added to radiation treatment for the palliation of multiple, unresectable brain metastases from non small cell lung cancer (NSCLC), is not yet well defined. Carboplatin and teniposide, however, are an interesting combination in this setting since they are active in NSCLC and because of encouraging results against brain metastases in other tumor types. METHODS: Twenty patients with brain metastases from NSCLC were treated with whole brain irradiation (total dose of 45 Gy) and chemotherapy (carboplatin, 300 mg/sm on day 1 and teniposide, 60 mg/sm on days 1, 2 and 3). RESULTS: Nine patients (45%) showed a complete remission of neurologic symptoms, and 7 (35%) an improvement. Neurologic signs disappeared in 8 patients (40%) and improved in 7 (35%). Three patients (15%) had partial (50%) regression of brain metastases at CT scan, and also showed response in other tumor sites. One other patient had a response of chest and liver lesions, while the cerebral metastases remained stable. Median survival was 7 months with a range of 1-9 months. Toxicity was mild, with no toxic deaths. CONCLUSIONS: Aggressive treatment can be taken into consideration also in the case of NSCLC patients with brain metastases and negative prognostic features. Their participation in clinical trials should be encouraged, since this will allow definition of the contribution of combined radiotherapy, chemotherapy and supportive care to the quality and duration of the patient's life.

Aged↗
PubMedDate not supplied

Failure of vinorelbine to produce responses in pretreated non-small cell lung cancer patients.

Fifteen patients with advanced non-small cell lung cancer, already treated with first-line chemotherapy, entered a protocol of palliative second-line treatment with the hemysynthetic vinca alkaloid vinorelbine (25 mg/sm weekly for two months). No patient obtained an objective response and the trial was stopped. Toxicity was not as mild as expected, with one treatment-related death due to leukopenia. It is concluded that single-agent vinorelbine, although effective as front-line chemotherapy for non-small cell lung cancer patients, is probably not suitable for palliative treatment of pretreated patients.

Aged↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Granisetron-dexamethasone combination for multiple day cisplatin.

Thirty-four, patients being given polychemotherapy schedules including cisplatin at the dose of 20 mg/sm for 5 days entered an antiemetic protocol with granisetron and dexamethasone at the doses of 3 mg and 8 mg respectively, both administered i.v. before cisplatin. A complete response (no episodes of vomiting) and a major response (< or = 2 episodes of vomiting) were observed in 14 and 12 patients respectively; the toxicity of the antiemetics was mild. It is concluded that the granisetron dexamethasone combination is able to achieve a high rate of antiemetic control in the special set of multiple day cisplatin treated patients.

Adult↗
PubMedDate not supplied

Biochemical modulation of 5-fluorouracil with methotrexate in advanced colorectal cancer patients pretreated with adjuvant 5-fluorouracil and leucovorin.

PURPOSE: 5-fluoracil (5-FU) remains the standard treatment in advanced colorectal cancer patients. An increasing number of recurring patients, however, have already received this drug as adjuvant after surgery. An attempt to increase 5-FU cytotoxicity through biochemical modulation is justified in this setting. In our study, a combination regimen of methotrexate followed by 5-FU, with leucovorin rescue, was employed. METHODS: Patients were required to have symptomatic, measurable, inoperable lesions from colorectal cancer, recurring after adequate radical surgery of the primary tumor and adjuvant 5-FU + leucovorin concluded at least 3 months before recurrence. Patients received methotrexate. 250 mg/m2 as a 2-hour i.v. infusion, followed by two doses of 5-FU, 500 mg/m2 as i.v. bolus 1 hour and 21 hours after the end of methotrexate infusion. Leucovorin rescue, 15 mg orally every six hours for 7 times, was started 1 hour after the second 5-FU dose. The cycle was repeated every 2 weeks. RESULTS: Twenty-two patients entered the trial, and 21 were evaluable. An objective response was observed in one patient (4.8%), 7 patients (33.3%) obtained tumor regression < 50% or disease stabilization. Thirteen patients (61.9%) progressed. Median survival in the whole group was 11 months. Subjective responses were observed in 7 patients (33.3%). Toxicity was mild. CONCLUSIONS: Biochemical modulation with methotrexate does not seem a satisfactory means of increasing 5-FU activity, when the patient has been previously exposed to 5-FU plus leucovorin. On the other hand, any possible advantages in terms of quality and prolongation of life with this schedule were obtained at the cost of very acceptable toxicity.

Adult↗
PubMedDate not supplied

Intensified M-VEC chemotherapy with G-CSF support as outpatient treatment for advanced bladder cancer.

The M-VAC regimen (methotrexate, vinblastine, doxorubicin and cisplatin) is widely used in the treatment of advanced or metastatic bladder cancer. In the present trial, an alternate week regimen of M-VEC (with epidoxorubicin instead of doxorubicin) supported by G-CSF (filgrastim) was evaluated. Eligible patients had metastatic or surgically unresectable bladder cancer, not previously treated with systemic chemotherapy. Treatment consisted of methotrexate 30 mg/m2 day 1, vinblastine 3 mg/m2 day 2, epidoxorubicin 60 mg/m2 day 2 and cisplatin 35 mg/m2 days 2 and 3. G-CSF was administered s.c. at the dose of 300 mcg from day 4 to day 11: the treatment was repeated every 2 weeks for six cycles. Twenty-one patients entered the study, and 19 received more than 1 cycle: 78.9% were able to receive full doses of M-VEC as scheduled. The treatment resulted feasible on an outpatient basis, with mild toxicity. Three complete responses (15.8%) and 9 partial responses (47.4%), with an overall objective response rate of 63.2%, were observed.

Aged↗
PubMedDate not supplied

A new schedule for etoposide, epidoxorubicin and cisplatin with granulocyte colony stimulating factor for advanced gastric cancer: a feasibility study.

A new polychemotherapy regimen has been developed for gastric cancer. Etoposide at the dose of 120 mg/m2 for three days, Epidoxorubicin at the dose of 30 mg/m2 on day 1 and Cisplatin at the dose of 40 mg/m2 on day 2 were administered to 26 advanced gastric patients every two weeks with the support of Granulocyte Colony Stimulating Factor from day 8 to day 12 of each cycle. The treatment was feasible with most cases (21/25) having received at least four cycles with a dose intensity > 85%, without life-threatening side effects. Toxicity was lower than that observed in the classical combinations of Etoposide-Anthracycline-Cisplatin.

Adult↗
PubMedDate not supplied

[Low-dose GM-CSF and dose intensity of antineoplastic agents].

Hematopoietic growth factors are cytokines able to modulate proliferation and differentiation of bone marrow progenitors. We have reviewed the effectiveness of GM-CSF in protecting marrow from chemotherapy-induced neutropenia, mainly in the setting of cyclic polychemotherapy; in particular, studies employing low doses of GM-CSF have been considered. G-CSF or GM-CSF may be particularly useful in situations in which the likelihood of a clinically relevant neutropenia is high, both because of higher dose intensity (obtained by intensification of doses of each cycle or by shortening of intervals between cycles) or because of pretreatment patient characteristics (old age, poor performance status, previous extensive chemotherapy or radiotherapy, experience of neutropenia in the previous cycles). GM-CSF at the conventional dose of 5 micrograms/kg was utilized to increase the etoposide dose to 900 mg/m2 in a chemotherapy program including also carboplatin and ifosfamide in patients with small cell lung cancer. In a randomized study by Ardizzoni et al., the administration of GM-CSF at the dose of 10 micrograms/kg following CEF program (cyclophosphamide, epirubicin and fluorouracil) was effective in reducing from 20 to 16 days the time interval among cycles. Since there is a relationship between GM-CSF dose levels and toxicity, it is attractive to investigate whether GM-CSF at doses lower than 5 micrograms/kg retains its myeloprotective effects, with a substantial reduction in its toxic effects. Grem et al. have observed that 3 micrograms/kg GM-CSF may allow the administration of 425 mg/m2 fluorouracil for five days; Reed et al. demonstrated that 600 mg/m2 carboplatin may be safely administered if protection with 3 micrograms/kg GM-CSF is applied; Kehoe et al. achieved acceleration of cyclophosphamide-cisplatin combination by GM-CSF at the dose of 3 micrograms/kg. We conclude that low dose GM-CSF deserves further evaluation in order to determine effectiveness and potential applications in the clinical practice.

Antineoplastic Agents↗