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N Zilembo

Publications and source records attributed to N Zilembo.

At least 37 records · Page 2Linked to original sources
PubMed1997

A multicentre, randomized, pharmacokinetic, endocrine and clinical study to evaluate formestane in breast cancer patients at first relapse: endocrine and clinical results. The Italian Trials in Medical Oncology (I.T.M.O.) group.

BACKGROUND: In postmenopausal breast cancer (BC) patients, tamoxifen (TAM) is frequently used in first-line therapy, and for those relapsing under TAM, aromatase inhibitors would be the drug of choice. Formestane, a new aromatase inhibitor, has been demonstrated to be as effective as TAM in first-line therapy. This trial was carried out to investigate the pharmacokinetics and antitumor activity of two formestane doses in BC patients at first relapse, as well as their effects on estrogen levels, evaluated by means of a new analytical method. PATIENTS AND METHODS: One hundred fifty-two postmenopausal BC patients were randomly given formestane 250 mg or 500 mg intramuscularly every two weeks. The blood samples for estrogen measurements were taken on the first day of therapy, at 4 and 10 weeks, and every 12 weeks thereafter. Tumor response was first evaluated after 2.5 months, and then every three months. RESULTS: Seventy-three patients received formestane 250 mg and 79 received 500 mg. After four weeks, plasma estrone, estradiol and estrone sulphate levels were significantly (P < 0.001) suppressed in both groups. The overall response rates were 30% and 40% on 250 mg and 500 mg, respectively. CONCLUSIONS: Both of the formestane doses are effective in reducing plasma estrogen levels in BC patients at first relapse, and the new analytical method improved the quality of results. The antitumor response was highly satisfactory.

Adult↗
PubMed1997

Serum markers of bone metastases in postmenopausal breast cancer patients treated with formestane.

Bone metabolism marker evaluation is expected to play an auxiliary role in the diagnosis and follow-up of bone metastases in patients affected by different types of neoplasms. In this study we have evaluated osteoblastic and osteoclastic markers in 18 patients with bone metastases from breast cancer at diagnosis and for 1 year of follow-up during treatment with the aromatase inhibitor formestane. Osteoblastic markers include the carboxy-terminal propeptide of type I procollagen, the bone-specific alkaline phosphatase and the bone GLA protein. The carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) was evaluated as a marker of osteoclastic activity. The patients were classified into three groups according to clinical response. A good correlation between marker level modifications and clinical evolution of skeletal metastases was observed for all the examined markers. Patients with progressive disease showed increasing levels of all markers, whereas patients in regression showed a reduction compared to the basal levels; patients with stable disease fell in between these two categories. We also found that basal ICTP values have prognostic significance: in the stable and progressive disease group they were higher than in the partial response group.

Alkaline Phosphatase↗
PubMed1996

Clinical efficacy of octreotide in the treatment of metastatic neuroendocrine tumors. A study by the Italian Trials in Medical Oncology Group.

BACKGROUND: The unsatisfactory control of neuroendocrine tumor growth with chemotherapy and/or interferon (IFN-2a) stimulated us to investigate the role of the somatostatin analogue octreotide (SMS 201.995), which is reported to be highly effective in controlling carcinoid syndrome symptoms. Octreotide has been used in a wide range of doses, and it was postulated that higher doses might lead to an objective response. METHODS: The aim of the present multicenter Phase II study was to determine the safety and efficacy of SMS 201.995 in controlling carcinoids and other neuroendocrine tumors. Fifty-eight patients were treated subcutaneously with 2 sequential doses of the drug (Sandostatina, Sandoz, Inc., S.b.A. Pharmaceuticals, Basel, Switzerland). The first 23 patients received 500 micrograms 3 times a day and the remaining 35 patients received 1000 micrograms 3 times a day. The treatment was continued until the tumor progressed. RESULTS: All of the patients were adequately treated and evaluated. The predominant histotype was carcinoid, although there were instances of medullary thyroid carcinoma, pancreatic islet cell tumors, and Merkel cell carcinoma. Carcinoid syndrome was documented in 16 patients and abnormal urinary 5-hydroxyindoloacetic acid excretion in 15. The median treatment duration was 5 months (range, 2-31 months). The responses were evaluated in three categories: tumor regression for tumor growth control, symptom response, and biochemical response. There was an effect on tumor growth in two patients with carcinoids. Symptomatic control was achieved in 73% of patients and a biochemical response in 77% of patients. In twenty-seven patients, the disease stabilized for at least 6 months (range, 6-32+). The median survival time for all patients was 22 months (range, 1-32+). CONCLUSIONS: In terms of tumor regression, octreotide is disappointing (partial response: 3%); symptomatic response and biochemical control are satisfactory. These data confirm that somatostatin analogues are comparable to interferons in the treatment of carcinoid syndrome, although other efforts are necessary to control tumor regression.

Adenoma, Islet Cell↗
PubMed1996

Phase II study of vinorelbine in patients with pretreated advanced ovarian cancer: activity in platinum-resistant disease.

PURPOSE: The aim of the study was to evaluate the activity of vinorelbine (VNLB) in a population of advanced ovarian cancer patients, with particular attention to defining its role in platinum-resistant disease. PATIENTS AND METHODS: Thirty-three patients were recruited and treated with VNLB 25 mg/m2 intravenously (IV) weekly. the median age was 53 years, performance status 0 to 2, and number of previous chemotherapy regimens two (range, one to five). Twenty-four patients were platinum-resistant; the remaining nine either were platinum-sensitive (four cases) or had undetermined sensitivity (five cases). RESULTS: The mean delivered dose-intensity of VNLB was 67% of the planned level, because 60% of the cycles were delayed due to neutropenia or anemia. Four partial responses (PRs) and one complete response (CR) were observed, for an overall response rate of 15% (95% exact confidence interval, 5.1% to 31.9%). All the responses occurred in the subgroup of 24 platinum-resistant cases, in whom the response rate was 21% (95% exact confidence interval, 7.1% to 42.1%). Seven patients became stabilized on VNLB, and 27% of the cases showed a reduction in serum cancer antigen 125 (CA 125) levels. G3/G4 side effects consisted of neutropenia, anemia, and worsening of preexisting peripheral neuropathy. No treatment-related deaths occurred. CONCLUSION: VNLB led to a 21% response rate in the population of heavily pretreated and platinum-resistant ovarian cancer patients. Further studies of VNLB alone or in combination with taxanes are warranted in patients with less pretreatment.

Adult↗
PubMed1995

Formestane: an effective first-line endocrine treatment for advanced breast cancer.

Formestane, a new selective aromatase inhibitor devoid of severe side-effects, has been shown to be active in patients with advanced breast cancer. To investigate the clinical activity and endocrinological effects of formestane as a first-line treatment, 52 patients were administered two different doses: 24 received 250 mg formestane and 28 received 500 mg formestane i.m. fortnightly. All of the patients had a performance status of 2 or less (ECOG scale), 34 (65%) had a disease-free interval of at least 2 years and 21 (40%) were both oestrogen-receptor- and progesterone-receptor-positive; 20 patients received hormone and 13, received chemotherapeutical adjuvant treatment. Objective responses were obtained in 8 patients in the 250-mg group (33%; 95% CI: 14%-52%) and in 13 patients in the 500-mg group (46%; 95% CI: 28%-64%). The median response duration in the two groups was respectively 11 and 12 months. E2 serum levels of oestradiol had significantly (P < 0.001) decreased to more than 40% below the baseline value in both groups after 15 days of treatment, and remained unchanged thereafter. Local and systemic tolerability was satisfactory. We conclude that formestane is an effective and well-tolerated agent in previously untreated patients, and that these results should be confirmed by further studies.

17-Hydroxycorticosteroids↗
PubMed1995

Combination goserelin and tamoxifen therapy in premenopausal advanced breast cancer: a multicentre study by the ITMO group. Italian Trials in Medical Oncology.

It has been suggested that tamoxifen may improve the efficacy of medical castration with luteinising hormone-releasing hormone analogues, but very few data have so far been published concerning the clinical and endocrinological activity of this therapeutic modality. In this phase II multicentre trial conducted by the Italian Trials in Medical Oncology group (ITMO), 64 premenopausal patients with hormone receptor-positive or unknown breast cancer were treated with monthly s.c. injections of goserelin 3.6 mg, in association with a tamoxifen daily dose of 20 mg, as first-line therapy for their advanced disease. All of the patients were evaluable for efficacy and there was an overall response rate of 41% (95% confidence interval 28-52%), with 7 of the 26 responders achieving complete remission. The median time to response was 4 months (range 2-17), and the median response duration was 13 months (range 6-37 +). Better responses were observed in soft tissues (51%); the response in visceral and bone metastases was respectively 19% and 37%. Serum concentrations of gonadotrophins and oestradiol were significantly decreased by the treatment, oestrogen levels being constantly suppressed to within the range observed in post-menopausal women. No significant change was detected in serum testosterone levels. In our experience, although it was not associated with any increased clinical efficacy, the concurrent use of goserelin and tamoxifen proved to be a feasible approach in the management of premenopausal advanced breast cancer.

Adult↗
PubMed1995

Endocrinological and clinical evaluation of exemestane, a new steroidal aromatase inhibitor.

The androstenedione derivative, exemestane (FCE 24304), is a new orally active irreversible aromatase inhibitor. Fifty-six post-menopausal advanced breast cancer patients entered this study to evaluate the activity of four low exemestane doses in reducing oestrogen levels. The drug's tolerability and clinical efficacy were also assessed. Exemestane was orally administered to four consecutive groups at daily doses of 25, 12.5, 5 and 2.5 mg, and the changes in oestrogen, gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate levels were evaluated. Drug selectivity was studied by measuring 17-hydroxycorticosteroid urinary levels. After 7 days of treatment, mean oestrone and oestradiol levels had decreased by respectively 64% and 65% (a decrease which was maintained over time); in the 2.5 mg group, oestrone sulphate levels also decreased by 74%. Gonadotrophin levels were significantly higher, whereas no changes in the other serum hormone levels or any interference with adrenal synthesis were detected. Treatment tolerability was satisfactory: nausea and dyspepsia were reported in 16% of patients. The overall objective response rate was 18%. In conclusion, exemestane is effective in reducing oestrogen levels at all of the tested doses and shows interesting clinical activity.

Adult↗
PubMed1994

Formestane as treatment of advanced breast cancer in elderly women.

AIMS AND BACKGROUND: The number of elderly people is increasing, and the proportion of breast cancer in female cancer patients older than 65 years is 26%. In elderly patients, hormone therapy is widely accepted as the treatment of choice, because of its efficacy and good tolerability compared to chemotherapy. The aim of this study was to evaluate the endocrinologic and clinical activity of formestane (4-hydroxyandrostenedione), a selective aromatase inhibitor, in elderly patients with advanced breast cancer. METHODS: Thirty-five patients older than 65 years, selected from a larger group, were given formestane (250 mg or 500 mg i.m. fortnightly). Patients were evaluable for tumor response after 4 doses of formestane. Blood samples were collected to evaluate E2, FSH, LH, SHBG and DHEAS serum levels at baseline and after 2, 4, 8, 12 and 24 weeks. RESULTS: Thirty patients had PS < or = 1 (ECOG) and only 5 patients had PS = 2. Twenty-six patients were ER positive. Previous hormonal treatment for metastatic disease had been given to 17 patients; only 1 case had received chemotherapy. The overall response rate was 51% (95% C.I. 35-67%) and the median response duration was 9.5 months. Three complete responses were observed on viscera. The best responses were obtained on soft tissues (59%); on bone and viscera the response was respectively 45% and 47%. Local and systemic tolerability was highly satisfactory. Formestane induced prolonged suppression of E2 levels in all of the patients, and a significant reduction in SHBG levels was also observed from month 2 onward. A statistically significant (P = 0.0001) rise in serum FSH was also observed during the therapy. CONCLUSIONS: The study showed that formestane induced a long-lasting suppression of E2 levels and a satisfactory overall response. In our opinion, the drug is an effective and well-tolerated approach in the management of advanced breast cancer in elderly patients.

Aged↗
PubMed1994

Ovarian function suppression with the gonadotrophin-releasing hormone (GnRH) analogue goserelin in premenopausal advanced breast cancer.

AIMS AND BACKGROUND: Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue that induces the suppression of gonadal steroidogenesis, and it could therefore be a medical alternative to irreversible surgical castration. We report the clinical and endocrine results from 40 goserelin-treated premenopausal patients with advanced breast cancer. METHODS: A depot formulation of the drug (3.6 mg s.c.) was administered fortnightly for the first 4 doses, and monthly thereafter. Gonadotrophins and estradiol (E2) levels were measured before and at specific times during the treatment. RESULTS: Objective responses were observed in 17 of the 38 evaluable patients (45%), six of whom achieved complete remission. The best responses were observed on soft tissues (65%). Castration E2 levels were achieved in all of the patients. CONCLUSIONS: Our results confirm that goserelin is as effective as surgical oophorectomy in premenopausal advanced breast cancer.

Adult↗
PubMed1994

Effect of two-4-hydroxyandrostenedione doses on serum insulin-like growth factor I levels in advanced breast cancer.

A number of endocrine treatments for advanced breast cancer seem to affect serum insulin-like growth factor I (IGF-I). The aim of our study was to investigate IGF-I levels in 33 postmenopausal patients with metastatic disease receiving the selective aromatase inhibitor 4-hydroxyandrostenedione: 250 mg (16 patients) or 500 mg (17 patients) i.m. fortnightly. Blood samples were collected before, and at one month and 3 months after the beginning of treatment for radioimmunoassay determinations. The median patient age was 56 and 60 years in the 250 and 500 mg groups respectively. Most patients had a disease free interval > or = 2 years and were oestrogen receptor positive. Objective responses were obtained in 3 patients (complete response, 1) in the 250 mg group, and in 7 patients (complete response, 3) in the 500 mg group. No significant IGF-I variations were seen in the 250 mg group, whereas a significant increase after 3 months (181.57 +/- 84.78 ng/ml versus 272.47 +/- 213.22 ng/ml, p = 0.0032) was observed in the 500 mg group. No IGF-I variations were seen between responsive and unresponsive patients in either treatment group. Our results in the 500 mg group are close to those obtained with aminoglutethimide and seem to agree with the hypothesis of an oestrogen-induced suppression of IGF-I circulating levels.

Aged↗
PubMed1994

Endocrinological and clinical evaluation of two doses of formestane in advanced breast cancer.

Formestane is a selective inhibitor of oestrogen synthesis by aromatase enzymes and induces disease regression in breast cancer patients. This phase II randomised study was carried out to determine whether there were any differences in the effects of two different doses of formestane on oestradiol (E2) serum levels and to evaluate the corresponding clinical activity in post-menopausal patients with positive or unknown oestrogen receptor status pretreated or not for advanced disease. Furthermore, possible drug interference with adrenal steroidogenesis was assessed by measuring 17-hydroxycorticosteroid (17-OHCS) urinary levels. A total of 143 patients entered the study and were randomly assigned to receive formestane 250 mg (72 patients) or formestane 500 mg (71 patients), both given i.m. every 2 weeks. In comparison with baseline, E2 serum levels decreased by an average of 40% after only 15 days and remained unchanged thereafter, with no difference being observed between the two doses. The values of 17-OHCS remained unchanged during treatment in both groups. Objective responses were 28% (19/69) in the 250 mg and 46% (31/68) in the 500 mg group. In conclusion, the two formestane doses were equally effective in reducing E2 levels without affecting adrenal function, and in inducing a considerable percentage of clinical responses.

17-Hydroxycorticosteroids↗
PubMed1994

Formestane: effective therapy in postmenopausal women with advanced breast cancer.

Aromatase inhibitors are a useful therapeutic option in the management of endocrine-dependent advanced breast cancer. Formestane (Lentaron) is the first irreversible aromatase inhibitor to be extensively investigated. In a phase II study to determine the effects of formestane on serum estradiol and urinary 17-hydroxycorticosteroid (17-OHCS) levels and to evaluate its clinical activity, 72 postmenopausal patients with advanced breast cancer were given formestane 250 mg intramuscularly every 2 weeks. Of 66 patients fully evaluable, 56 were estrogen receptor (ER) positive, and 43 had a disease-free interval > or = 2 years. Metastases were assessable in soft tissue (53%), bone (53%) and viscera (47%); 34 patients had 1, 32 had > or = 2 metastatic lesions. Serum estradiol levels fell significantly (p < 0.01) after 2 weeks and remained unchanged thereafter, whereas urinary 17-OHCS levels did not change during treatment. Objective responses were obtained in 19 patients (29%), of whom 8 had complete response. In relation to disease sites, similar responses were obtained in soft tissue (33%) and viscera (30%), whereas response in bone was 18%. The overall tolerability of formestane was satisfactory, and only two patients complained of local side effects. We conclude that formestane is an effective aromatase inhibitor in postmenopausal patients with hormone-dependent breast cancer, and does not interfere with adrenal steroidogenesis.

17-Hydroxycorticosteroids↗
PubMed1993

Medical treatment of neuroendocrine tumors.

BACKGROUND: Tumors of the neuroendocrine system are characterized by amine precursor uptake and decarboxylation, and they represent a heterogeneous group of carcinomas including carcinoids, islet cell carcinomas of the pancreas, medullary thyroid carcinomas and Merkel cell carcinomas. Their similar cytochemical and ultrastructural properties sustain the hypothesis of a common embryologic origin within the neural crest. Many of these tumors grow slowly, and reducing tumor burden represents the treatment of choice. However, when surgery is not feasible, medical treatment has to be considered. Therapeutic approaches in metastatic disease often do not consider the different biologic behaviors of these neoplasms. Moreover, efficacy of the treatment is associated with lack of a clear definition of the type of response: objective, symptomatic or biochemical. METHODS: In this review we have analyzed the different medical approaches used in the treatment of neuroendocrine tumors in an attempt to define their precise role in the different neoplasms. RESULTS: In carcinoid tumors, immunotherapy and the somatostatin analogue can be efficaciously used for the control of carcinoid syndrome. For inhibition of tumor growth, chemotherapy should be used only in patients with rapidly progressive disease, and the results are still unsatisfactory. CONCLUSIONS: Although all these tumors appear to have similar cytochemical properties, the responsiveness of the various neoplasms is very different. In the future, a specific treatment modality and a clear definition of the type of response (objective, symptomatic or biochemical) need to be defined for each type of neuroendocrine tumor.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Treatment of metastatic carcinoids and other neuroendocrine tumors with recombinant interferon-alpha-2a. A study by the Italian Trials in Medical Oncology Group.

BACKGROUND: Using a wide range of interferon (IFN) doses and schedules, a number of authors have found them to be active against neuroendocrine tumors. METHODS: To verify the clinical activity of IFN, 49 evaluable patients with advanced stage low- and intermediate-grade neuroendocrine tumors were treated with recombinant IFN-alpha-2a at a daily dose of 6 x 10(6) IU intramuscularly for 8 weeks, and 3 times weekly thereafter. The predominant histotype was carcinoid, although a few cases had malignant islet cell tumors, medullary thyroid carcinoma, Merkel cell carcinoma, or other neuroendocrine tumors. All of the patients had measurable lesions and most had multiple sites. Carcinoid syndrome was present in 14 cases. RESULTS: After a median treatment duration of 6 months, complete regression was achieved in 1 of the 7 cases of medullary thyroid carcinoma, and partial response was observed in 4 of 34 carcinoids. Response duration ranged from 1-11 months. Control of the syndrome was obtained in nine patients and a greater than or equal to 50% reduction of 5-hydroxyindoleacetic acid in eight patients. The treatment was well-tolerated. The most frequently observed side effects were fever, flu-like syndrome, and leukopenia. After 12 months of recombinant IFN-alpha-2a, 15 cases in progression and 4 with stable disease or partial response received another treatment (either radiometabolic therapy with I131 metaiodobenzylguanidine or polychemotherapy with streptozotocin plus epirubicin). CONCLUSIONS: The use of recombinant IFN-alpha-2a at these doses is well-tolerated and effective in controlling carcinoid syndrome (complete remission plus partial remission, 64%), although it has limited activity on tumor growth inhibition. No definitive data can be given for the other protocol treatments.

Adult↗
PubMed1993

Efficacy and tolerability of 4-hydroxyandrostenedione (4-OHA) as first-line treatment in postmenopausal patients with breast cancer after adjuvant therapy.

Aromatase inhibitors are known to be effective in the treatment of advanced postmenopausal breast cancer. To assess the efficacy of the aromatase inhibitor 4-hydroxyandrostenedione (4-OHA) as first-line treatment in patients who were either resistant to or had relapsed after adjuvant therapy, 50 eligible patients received intramuscular 4-OHA either 250 mg or 500 mg fortnightly until disease progression or severe adverse events. Of the 43 patients evaluable for clinical response (UICC criteria), 15 (36%) showed objective response (CR+PR), 6 (14%) stable disease (SD). In relation to disease site, objective responses were obtained in 55% of cases with soft tissue metastases (16/29); in 33% with visceral metastases (8/24), and in 24% with bone involvement (5/21). In relation to previous adjuvant treatment, there were eight objective responses among the 17 patients treated with chemotherapy (47%), and seven objective responses among the 24 treated with tamoxifen (29%). The treatment was well tolerated. These results support the hypothesis that adjuvant therapy, whether hormonal or chemotherapy, may make patients less responsive to subsequent treatment.

Aged↗
PubMed1993

Treatment of carcinoid syndrome with recombinant interferon alpha-2a.

The prognosis and the quality of life of patients with carcinoid tumors is related either to symptoms from the substances secreted or to progressive tumor growth. Medical treatment with cytotoxic agents is of marginal value for increasing life expectancy and reducing clinical symptoms. Recent studies with interferon have shown interesting results. In the present investigation, 22 patients with carcinoid tumors and syndrome were treated with recombinant interferon alpha-2a (r-IFN alpha-2a) at the dose of 6 x 10(6) IU intramuscularly daily for 8 weeks and three times weekly thereafter. The primary tumor was localized in the foregut (n = 11), midgut (n = 7), hindgut (n = 1), and unknown site (n = 3). Most cases had liver metastasis. Seventeen patients had elevated 5-hydroxyindoloacetic acid (5-HIAA) excretion and 5 had flushing and/or diarrhea as the only clinical manifestation. Six cases presented a complete syndrome (flushing, diarrhea and 5-HIAA excretion). Control of symptoms was obtained in 80% and a 5-HIAA level reduction in 58% of the patients. The interferon treatment was more effective for control of the carcinoid syndrome than for control of tumor growth. The treatment was well tolerated and fever, myalgia, anorexia and fatigue were the most frequent side-effects.

Adult↗