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Biomedical subjects

N Zilembo

Publications and source records attributed to N Zilembo.

45 records · Page 3Linked to original sources

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↗

Reversal of resistance to doxifluridine and fluorouracil in metastatic colorectal cancer: the role of high-dose folinic acid.

The benefits from medical treatment in colorectal cancer are limited. Fluorouracil remains the only recognized drug, and how to treat unresponsive patients is still debated. To evaluate the role of folinic acid (FA) in circumvence resistance in colorectal cancer, 28 patients pretreated with fluoropyrimidine were candidated to receive one of the following schedules: fluorouracil (600 mg/m2) associated with FA (500 mg/m2) weekly for 6 weeks (Regimen A: 21 cases), or fluorouracil (370 mg/m2) plus FA (200 mg/m2) daily for 5 days every 4 weeks (Regimen B: 7 cases). Fourteen patients were pretreated with doxifluridine, a new fluoropyrimidine derivative with a peculiar mechanism of action, and the remaining 14 patients with fluorouracil. All but 2 patients were unresponsive to first-line treatments. When the treatment began, the median age of the patients was 60 years (range, 30-68). The performance status (ECOG) was 0/1 in 25 of them, and the primary tumor was in the colon and rectum in 19 and 9 patients, respectively. Sites of disease were liver (64%), lung (35%), local recurrence (10%) and peritoneum (10%). A median of 3 cycles (range, 1-7) was delivered, and no objective response was observed in the group of patients pretreated with doxifluridine or in the group pretreated with fluorouracil. In 5 cases a significant decrease in baseline CEA values was observed. Therapy was well tolerated, and no grade 4 toxicity was encountered. Severe toxicity was limited and included diarrhea (7 patients), stomatitis (1 patient) and nausea/vomiting (1 patient). High-dose FA has no role in reversing resistance to fluoropyrimidine, and other mechanisms of refractoriness are surely involved. FA should be associated with fluoropyrimidine as first-line therapy together with other biochemical modulators. Further rescue therapies need to be developed.

Adult↗

Plasma postheparin diamine oxidase in patients with small intestinal lymphoma.

Diamine oxidase (DAO) is an enzyme located almost exclusively in villus tip enterocytes. Its plasma activity is enhanced by intravenous heparin which releases the enzymes from small bowel enterocytes into the blood. Plasma postheparin DAO (PHD) values have been shown to be significantly lower in patients with malabsorption and villous atrophy, thus suggesting that PHD reflects the mature enterocytic mass. In this study we have assayed PHD in five patients with small bowel lymphoma (two with immunoproliferative small intestinal disease [IPSID] and three with non-IPSID lymphoma) associated with malabsorption syndrome and small bowel mucosa atrophy. The PHD test was performed at diagnosis, after partial or complete remission induced by chemotherapy, and during the follow-up. The PHD values, very low at diagnosis (0.66 +/- 0.12 U/ml), increased during chemotherapy and reached the normal range (greater than 3.7 U/ml) when complete remission occurred. The PHD values rapidly and consistently decreased whenever the disease relapsed. Our data indicate that in patients with small bowel lymphoma PHD test is a sensitive marker of small bowel mucosa damage and suggest that it could be useful in monitoring the recovery of mucosal lesions induced by chemotherapy.

Adolescent↗

The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels.

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels were measured in two groups of postmenopausal women with advanced breast cancer, who received the aromatase inhibitor letrozole 0.5 or 2.5 mg p.o. once daily. Blood samples were obtained from 15 patients in each dose group at baseline, and one and three months after starting therapy. Circulating IGF-I and IGFBP-3 concentrations were determined by means of radioimmunoassay. In both dosage groups a statistically significant increase in the IGF-I levels was observed during three months of letrozole treatment (P=0.003). In addition, the multiple testing procedure yielded in the whole patient population a significant result in the comparison between mean IGF-I values after three months of therapy and those observed at baseline (P=0.004), the estimated average increase being of 24%. No significant result was obtained in the analysis for the dose effect (P=0.077) and for the time x dose interaction (P=0.208). Circulating IGFBP-3 levels did not appear to be affected by letrozole treatment in either of the dose groups. This is the first report concerning the short-term effects of letrozole on components of the IGF system in breast cancer patients; further investigations are warranted in order to confirm these preliminary data.

Aged↗

Goserelin in premenopausal advanced breast cancer: clinical and endocrine evaluation of responsive patients.

Medical ovariectomy with goserelin is an alternative to surgical oophorectomy. To evaluate the relationship between tumor regression and endocrine changes induced by therapy, 40 premenopausal patients with advanced breast cancer were given 3.6 mg of goserelin subcutaneously fortnightly for the first 4 doses and every 28 days thereafter. We have made a particular analysis of the clinical and endocrine profile of responsive patients. Objective responses were observed in 17 of the 38 evaluable patients (45%), 6 cases achieving complete remission. Serum estradiol was suppressed in castrated women, although there was a tendency towards an increase in serum follicle-stimulating hormone over time. No statistically significant difference was observed in the hormonal profiles of patients experiencing a complete or partial response. Our experience confirms that goserelin is as effective as oophorectomy and that there is a clear correspondence between clinical response and drug-induced estrogen suppression.

Adult↗

Activity of formestane in de novo tamoxifen-resistant patients with metastatic breast cancer.

In order to assess the feasibility of a sequential hormonal treatment after tamoxifen failure, 24 postmenopausal advanced breast cancer patients (median age 60 years; ECOG PS < or = 1) were treated with formestane (4-hydroxyandrostenedione) 250 mg i.m. fortnightly; 19 patients were estrogen receptor-positive. The sites of metastatic disease were soft tissue in 22 patients, viscera in 9 and bone in 18. The patients were considered evaluable for tumor response after four doses of formestane. Objective responses were observed in 8/24 patients (33%) with one complete and seven partial responses. The median response duration was 9.5 months. The complete response was obtained on skin. We conclude that although the number of complete responses appears to be unsatisfactory, de novo tamoxifen-resistant breast cancer patients are suitable for further hormonal treatment with formestane.

Aged↗

Cell kinetics and tumor-associated antigen expression in human mammary carcinomas.

Twenty-six primary breast carcinomas were studied to evaluate cell proliferation as assessed by thymidine labeling index (TLI), and antigenic phenotype, as defined by immunohistochemistry using eight monoclonal antibodies (MAbs) to tumor-associated antigens (TAAs). The majority of tumors had low TLI values. Reactivity to MAbs B72.3, CC49, CC83 (anti TAG 72), COL-12 (anti CEA) and MOv2 (against a tumor-associated mucoprotein) was restricted to less than 50% of the tumors studied, while MAbs B1.1 (anti CEA), MBrl and MBr8 (to tumor-associated carbohydrates) reacted with greater than 50% of the cases. Correlations between expression of TAAs and proliferative activity showed that the tumors could be divided into three groups, two characterized by either high proliferative activity and absence of antigenic expression or low proliferative activity and strong antigenic expression, and the third showing no relation between these two biological features. We defined two antigenic phenotypes associated with specific cellular kinetics: one characterized by negative immunoreaction with MAbs, CC49, CC83 and COL-12 and high proliferative activity; the other characterized by intense immunoreactivity with these antibodies and low proliferative activity. The data suggest that cell proliferation and antigenic phenotype may define biologic subsets of breast carcinomas.

Antibodies, Monoclonal↗

[131I]metaiodobenzylguanidine therapy in carcinoid tumors.

Our experience with [131I]metaiodobenzylguanidine (131I-MIBG) therapy in two patients with carcinoid tumor is described. These patients were selected because of multiple areas of uptake on 131I-MIBG scan, consistent with the extent of the disease. Both patients presented diarrhea and liver metastases. Para-aortical lymphonodes and skeletal metastases were present in the first and the second patient, respectively. Previous treatment involved r-alpha-interferon, surgery or radiotherapy. In both cases 131I-MIGB therapy was started in December 1990 and is still continuing. No haematologic or hepatic side-effects have been observed. Mild hypotension (90/60 mmHg) occurred in one patient during the first course of therapy and was resolved by corticoid treatment. A stabilization of disease and a progressive reduction of diarrhea have been observed in both patients. In the second patient an initial decrease in liver metastases was confirmed by ultrasonography 7 months after the beginning of therapy.

3-Iodobenzylguanidine↗