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N Zilembo - One of the best experts on this subject based on the ideXlab platform.

  • the estrogen suppression after sequential treatment with Formestane in advanced breast cancer patients
    Biomedicine & Pharmacotherapy, 2004
    Co-Authors: N Zilembo, E Bajetta, A Martinetti, Ettore Bichisao, Ignazia La Torre, Paolo Bidoli, Raffaella Longarini, Tindara Portale, Ettore Seregni, Emilio Bombardieri
    Abstract:

    Abstract In postmenopausal patients, estrogens have an important role in breast cancer growth and aromatase inhibitors (AI) suppress the aromatase enzyme system which converts androgens into estrogens. The aim of this study was to evaluate the effect on estrogen suppression of Formestane 250 mg i.m. fortnightly, given immediately after the failure of a previous treatment with non-steroidal AI. Twenty-two advanced breast cancer patients progressing on letrozole, anastrozole and aminoglutethimide entered the study. At the beginning of the study, the serum estrogen levels were suppressed by the previous treatment with non-steroidal AI, and the following treatment with Formestane moderately maintained this suppression; in four patients serum estrogen levels increased fivefold after 10 weeks. Neither complete nor partial responses were observed; 11 patients (50%) showed a stable disease lasting ≥6 months, and the median time to progression was 6 months (range 3–9 months). No correlation was observed between clinical responses and serum estrogen suppression. Tolerability was satisfactory, and no patient withdrew from the study due to adverse events. In conclusion, Formestane has demonstrated a moderate activity in estrogen suppression, and there is evidence that, at the failure of a previous treatment with non-steroidal AI, the sequential use of steroidal AI is feasible. This approach can be used in clinical practice in order to offer a disease control with a satisfactory quality of life.

  • the luteinising hormone releasing hormone analogue triptorelin with or without the aromatase inhibitor Formestane in premenopausal breast cancer effects on bone metabolism markers
    The Journal of Steroid Biochemistry and Molecular Biology, 2000
    Co-Authors: A Martinetti, N Zilembo, L Ferrari, Luigi Celio, Luigi Mariani, Rosalba Miceli, Maria Di Bartolomeo, L Toffolatti, P Pozzi, Ettore Seregni
    Abstract:

    Abstract Background: the combination of a luteinising hormone–releasing hormone (LH–RH) analogue and an aromatase inhibitor (AI) induces greater oestrogen suppression than the analogue alone in premenopausal breast cancer. However, very few data on the biological effects of such a combination are currently available. Aim of the study: the short-term effects of treatment with the LH–RH analogue triptorelin alone or in association with the AI Formestane on bone metabolism were investigated in premenopausal breast cancer. Circulating levels of the bone formation markers carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP and PINP) and the bone resorption marker cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were assessed. In addition, serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and interleukin 6 (IL-6) were evaluated. Patients and methods: twenty-one patients with advanced breast cancer were randomly given triptorelin monthly alone (n=10, arm A) or in combination with Formestane fortnightly (n=11, arm B). Blood samples were collected over a 3-month period. Results: serum PICP and PINP levels increased significantly over time (P=0.0065 and 0.0197 in arm A and B, respectively); no change in ICTP levels was observed. A rise in IGF-I and IGFBP-3 levels was seen in each treatment group, but only the increase in IGF-I was significant (P=0.0138, always). The on-treatment levels of the bone turnover markers and IGF-system components were inversely correlated with serum oestrogens. Neither treatment modalities significantly affected serum IL-6 levels over time. No difference in the behaviour of any of the assessed biomarkers was observed between patients with or without skeletal metastases. Conclusion: it is worth noting that complete oestrogen depletion, at least in our case series, seems to increase only osteoblastic activity markers. The observed modifications appear to be related to oestrogen depletion per se rather than the degree of oestrogen suppression or the different therapeutic regimen administered.

  • a multicentre randomized pharmacokinetic endocrine and clinical study to evaluate Formestane in breast cancer patients at first relapse endocrine and clinical results
    Annals of Oncology, 1997
    Co-Authors: E Bajetta, N Zilembo, Roberto Buzzoni, Cristina Noberasco, A Martinetti, L Ferrari, Sandro Barni, Giuseppe Schieppati, A Jirillo, M Amichetti
    Abstract:

    Summary 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 pharmaco-kinetics 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.

  • serum markers of bone metastases in postmenopausal breast cancer patients treated with Formestane
    Tumor Biology, 1997
    Co-Authors: A Martinetti, E Bajetta, N Zilembo, Cristina Noberasco, L Ferrari, Ettore Seregni, S Massaron, Lorenza Rimassa, Emilio Bombardieri
    Abstract:

    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 ev

  • activity of Formestane in de novo tamoxifen resistant patients with metastatic breast cancer
    Oncology, 1995
    Co-Authors: Cristina Noberasco, E Bajetta, N Zilembo, C Bartoli, Aldo Bono, A Di Leo, Federico Cappuzzo, Ettore Bichisao
    Abstract:

    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 ≤ 1) were treated with fo

R C Coombes - One of the best experts on this subject based on the ideXlab platform.

  • estrogen receptor directed neoadjuvant therapy for breast cancer results of a randomised trial using Formestane and methotrexate mitozantrone and mitomycin c mmm chemotherapy
    Annals of Oncology, 2001
    Co-Authors: J C Gazet, H T Ford, Richard Gray, C Mcconkey, R Sutcliffe, J Quilliam, V Makinde, S Lowndes, R C Coombes
    Abstract:

    Summary Background We wanted to determine whether neoadjuvant systemic chemoendocrine therapy guided by the estrogen receptor (ER) status of the primary breast cancer, followed by conventional surgery and/or radiotherapy, reduces local and distant recurrence and improves survival compared with adjuvant treatment given conventionally postoperatively. Patients and methods Two hundred ten patients with primary breast cancer (T1–T4, N0, N1–2) were randomised to receive treatment with neoadjuvant chemoendocrine therapy or conventional post-operative chemoendocrine therapy. Systemic therapy was based on the estrogen receptor (ER) status of the primary tumour obtained by trucut core biopsy. ER-negative patients received MMM chemotherapy (methotrexate (30 mg/m2), mitozantrone (7 mg/m2) and mitomycin (7 mg/m2) three-weekly for three months and ER-positive patients who were premenopausal received goserelin (3.75 mg monthly), and post menopausal women Formestane (250 mg every two weeks) over three months. Results With a minimum of five years follow-up, there is no evidence of any survival benefit from the pretreatment neoadjuvant therapy regimen, with five year overall survival being 79% ± 4.7% (neoadjuvant) and 87% ± 3.4% (adjuvant). Similarly, there was no apparent benefit in terms of disease-free survival. There was, however, a significant reduction in the incidence of distant metastases in responders (4 of 51; 8%) compared with non-responders (17 of 49; 35%) (P Conclusion In this study neoadjuvant treatment with endocrine or chemotherapy provided no obvious survival benefit to women with breast cancer. However, it does allow avoidance of surgery in some cases. Also, the patients whose tumours respond to neoadjuvant systemic therapy have a lower incidence of distant metastases after five year follow-up compared to those whose tumours fail to respond.

  • open comparative trial of Formestane versus megestrol acetate in postmenopausal patients with advanced breast cancer previously treated with tamoxifen
    The Breast, 2000
    Co-Authors: M Freue, R C Coombes, M Kjaer, C Boni, J Joliver, F Janicke, H B Willemse, S Van Belle, R Perezcarrion, J Zieschang
    Abstract:

    Abstract The aim of the trial was to compare efficacy and safety of the aromatase inhibitor Formestane (250 mg i.m. given every 2 weeks) with the progestin megestrol acetate (160 mg administered orally once daily), as second-line therapy in postmenopausal patients with advanced breast cancer previously treated with tamoxifen. A total of 547 patients were enrolled. Analyses revealed no statistically significant or clinically relevant difference between treatments with respect to time endpoints. In the intent-to-treat analysis, the median values for time to failure and overall survival for Formestane were 169 and 561 days, respectively. The corresponding values for megestrol acetate were 169 days and 597 days, respectively. Overall response rates were comparable for Formestane and megestrol acetate (16.3% vs 20.3%). Formestane was better tolerated than megestrol acetate. In the megestrol acetate group, cardiovascular events, weight increase, and vaginal haemorrhage were significantly more frequent than in the Formestane group. Thus, Formestane is a suitable alternative to progestins in patients previously treated with tamoxifen.

  • vorozole results in greater oestrogen suppression than Formestane in postmenopausal women and when added to goserelin in premenopausal women with advanced breast cancer
    Breast Cancer Research and Treatment, 1999
    Co-Authors: M Dowsett, D Doody, S Miall, A Howes, J English, R C Coombes
    Abstract:

    The high potency and selectivity of new aromatase inhibitors has translated to greater efficacy and improved tolerability in comparison with established second-line hormonal agents for advanced breast cancer in phase III clinical trials. Two pharmacological studies are reported which assess the use of one of these inhibitors, vorozole, in combination or comparison with well-established methods of oestrogen deprivation in pre and postmenopausal patients. When combined with the gonadotrophin-releasing hormone agonist (GnRHa) goserelin in 10 premenopausal patients, vorozole markedly enhanced the suppression of serum levels of oestrone, oestradiol and, oestrone sulphate beyond that achieved by goserelin alone (by a mean 74%, 83%, and 89%, respectively). The combination was well-tolerated and had no significant effects on androgen levels. Vorozole was compared with Formestane in 13 postmenopausal women and serum oestrone, oestradiol, and oestrone sulphate levels were suppressed by 47%, 30%, and 70%, respectively, more by vorozole than by the steroidal aromatase inhibitor. Again the tolerability was excellent. The plasma oestrogen levels in the postmenopausal patients on vorozole were lower than in the premenopausal patients on goserelin plus vorozole, indicating that ovarian oestrogen synthesis may be relatively resistant to aromatase inhibition, even during GnRHa treatment. Thus, in both pre and postmenopausal patients substantially greater suppression of oestrogen can be achieved by vorozole compared with alternative approaches. Existing clinical-pharmacological correlates suggest that these increases in pharmacological effectiveness may result in enhanced clinical effectiveness.

  • anastrozole shows evidence of activity in postmenopausal patients who have responded or stabilised on Formestane therapy
    European Journal of Cancer, 1999
    Co-Authors: C Harperwynne, R C Coombes
    Abstract:

    Abstract Formestane (Lentaron™) and anastrozole (Arimidex™) are in clinical use as second-line treatments for advanced breast cancer. Current practice is often to use an aromatase inhibitor only once before switching to third-line agents such as progestins. There are few clinical data on the sequential use of aromatase inhibitors. We therefore decided to study the clinical effects of anastrozole in postmenopausal patients with advanced breast cancer who had already received Formestane. 21 patients were recruited. When receiving Formestane 2/21 (10%) achieved a partial response (UICC criteria) and 10/21 (48%) stable disease. Of these 12 patients, 9 achieved further stable disease on anastrozole (78%; 7/9 oestrogen receptor positive). 4 of 9 patients who progressed on Formestane also stabilised on anastrozole, of whom 3 had oestrogen receptor positive breast carcinomas. The explanation of this second stabilisation may relate to a further fall in oestradiol levels. We feel these results are of interest and warrant further clinical investigation.

  • an endocrine and pharmacokinetic study of four oral doses of Formestane in postmenopausal breast cancer patients
    European Journal of Cancer, 1992
    Co-Authors: M Dowsett, A Mehta, N King, I E Smith, T J Powles, Robert Stein, R C Coombes
    Abstract:

    43 postmenopausal breast cancer patients were treated orally with the aromatase inhibitor Formestane (4-hydroxyandrostenedione) at daily doses of 62.5, 125, 250 or 500 mg for 4 weeks followed by 250 mg daily for a further 4 weeks. For some patients, 62.5 mg did not suppress serum oestradiol levels maximally. The doses of 250 and 500 mg did not differ in their effectiveness. Oestrone levels were suppressed by all doses of Formestane but no consistent changes of aldosterone, cortisol or 17-hydroxyprogesterone occurred. Serum levels of sex hormone binding globulin fell by about 15% during treatment with 250 mg Formestane reflecting its minor androgenic activity. The maximum concentration and area under the curve of serum Formestane levels after the first dose varied in an approximately linear manner with dose. It is concluded that Formestane is an effective, specific suppressant of oestradiol levels via the oral route requiring no more than 250 mg to be given daily.

E Bajetta - One of the best experts on this subject based on the ideXlab platform.

  • the estrogen suppression after sequential treatment with Formestane in advanced breast cancer patients
    Biomedicine & Pharmacotherapy, 2004
    Co-Authors: N Zilembo, E Bajetta, A Martinetti, Ettore Bichisao, Ignazia La Torre, Paolo Bidoli, Raffaella Longarini, Tindara Portale, Ettore Seregni, Emilio Bombardieri
    Abstract:

    Abstract In postmenopausal patients, estrogens have an important role in breast cancer growth and aromatase inhibitors (AI) suppress the aromatase enzyme system which converts androgens into estrogens. The aim of this study was to evaluate the effect on estrogen suppression of Formestane 250 mg i.m. fortnightly, given immediately after the failure of a previous treatment with non-steroidal AI. Twenty-two advanced breast cancer patients progressing on letrozole, anastrozole and aminoglutethimide entered the study. At the beginning of the study, the serum estrogen levels were suppressed by the previous treatment with non-steroidal AI, and the following treatment with Formestane moderately maintained this suppression; in four patients serum estrogen levels increased fivefold after 10 weeks. Neither complete nor partial responses were observed; 11 patients (50%) showed a stable disease lasting ≥6 months, and the median time to progression was 6 months (range 3–9 months). No correlation was observed between clinical responses and serum estrogen suppression. Tolerability was satisfactory, and no patient withdrew from the study due to adverse events. In conclusion, Formestane has demonstrated a moderate activity in estrogen suppression, and there is evidence that, at the failure of a previous treatment with non-steroidal AI, the sequential use of steroidal AI is feasible. This approach can be used in clinical practice in order to offer a disease control with a satisfactory quality of life.

  • a multicentre randomized pharmacokinetic endocrine and clinical study to evaluate Formestane in breast cancer patients at first relapse endocrine and clinical results
    Annals of Oncology, 1997
    Co-Authors: E Bajetta, N Zilembo, Roberto Buzzoni, Cristina Noberasco, A Martinetti, L Ferrari, Sandro Barni, Giuseppe Schieppati, A Jirillo, M Amichetti
    Abstract:

    Summary 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 pharmaco-kinetics 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.

  • serum markers of bone metastases in postmenopausal breast cancer patients treated with Formestane
    Tumor Biology, 1997
    Co-Authors: A Martinetti, E Bajetta, N Zilembo, Cristina Noberasco, L Ferrari, Ettore Seregni, S Massaron, Lorenza Rimassa, Emilio Bombardieri
    Abstract:

    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 ev

  • activity of Formestane in de novo tamoxifen resistant patients with metastatic breast cancer
    Oncology, 1995
    Co-Authors: Cristina Noberasco, E Bajetta, N Zilembo, C Bartoli, Aldo Bono, A Di Leo, Federico Cappuzzo, Ettore Bichisao
    Abstract:

    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 ≤ 1) were treated with fo

  • Formestane an effective first line endocrine treatment for advanced breast cancer
    Journal of Cancer Research and Clinical Oncology, 1995
    Co-Authors: N Zilembo, E Bajetta, Roberto Buzzoni, Cristina Noberasco, G Vicario, Aldo Bono, A Laffranchi, Giuseppa Biasi, Stella Dolci, Ettore Bichisao
    Abstract:

    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.

Per Eystein Lonning - One of the best experts on this subject based on the ideXlab platform.

  • pharmacokinetics and metabolism of Formestane in breast cancer patients
    The Journal of Steroid Biochemistry and Molecular Biology, 2001
    Co-Authors: Per Eystein Lonning, Jurgen Geisler, Dag Clement Johannessen, Hanspeter Gschwind, Felix Waldmeier, Werner Schneider, Bruno Galli, Tammo Winkler, Wolfgang Blum, Hanspeter Kriemler
    Abstract:

    Formestane (Lentaron(R), 4-hydroxyandrostenedione) is a steroidal aromatase inhibitor used for treatment of advanced breast cancer. Clinically, it is administered as a depot form once fortnightly by intramuscular (i.m.) injection. To investigate the pharmacokinetics, bioavailability and metabolism of the drug, seven patients received single 250 mg i.m. doses of commercial Formestane on Days 0, 21, 35, 49 and 63 of this trial. On Day 63, three of the patients received an additional single intravenous (i.v.) pulse dose of 1 mg of 14C-labelled Formestane. The plasma kinetics after i.m. dosing confirmed a sustained release of Formestane from the site of injection. Within 24-48 h of the first dose, the circulating drug reached a C(max) of 48.0+/-20.9 nmol/l (mean+/-S.D.; N=7). At the end of the dosing interval, after 14 days, the plasma concentration was still at 2.3+/-1.8 nmol/l. The kinetic variables did not significantly change during prolonged treatment. Intramuscular doses appear to be fully bioavailable. Following i.v. injection of 14C-Formestane, the unchanged drug disappeared rapidly from plasma, the terminal elimination half-life being 18+/-2 min (N=3). Plasma clearance, CL was 4.2+/-1.3 l/(h kg) and the terminal distribution volume V(z) was 1.8+/-0.5 l/kg. The drug is mainly eliminated by metabolism, renal excretion of metabolites accounting for 95% of dose. The excretory balance of 14C-compounds in urine and faeces totals up to 98.9+/-0.8% of the i.v. dose after 168 h. The 14C-compounds in plasma and urine were separated by HPLC, and three major metabolites were submitted to structural analysis by MS, NMR and UV spectroscopy. One of the metabolites is the direct 4-O-glucuronide of Formestane. The other two represent 3-O-sulfates of the exocons 3beta,4beta-dihydroxy-5alpha-androstane-17-one and 3alpha,4beta-dihydroxy-5alpha-androstane-17-one, their ratio being 7:3. These exocons are formed by stereoselective 3-keto reduction, accompanied by reduction of the 4,5-enol function. The exocons do not inhibit human placental aromatase activity in vitro.

  • pharmacological profiles of exemestane and Formestane steroidal aromatase inhibitors used for treatment of postmenopausal breast cancer
    Breast Cancer Research and Treatment, 1998
    Co-Authors: Per Eystein Lonning
    Abstract:

    Steroidal aromatase inhibitors like Formestane and exemestane are useful drugs for endocrine treatment of postmenopausal breast cancer. In addition, these drugs should be considered valuable probes to explore the biology of breast cancer with particular emphasis on possible relations between the degree of estrogen suppression and clinical efficacy and the possible role of intratumor estrogen synthesis. The fact that steroidal and non-steroidal aromatase inhibitors bind to different parts of the aromatase enzyme suggests these drugs may act in concert aggravating plasma estrogen suppression. Thus, use of a steroidal and a non-steroidal aromatase inhibitors in concert may be one way to improve breast cancer treatment and may also provide important information to a better understanding of the dose-response relationship between estrogen suppression and clinical effects. Further, the finding that patients progressing on non-steroidal aromatase inhibitors may respond to Formestane as well as exemestane suggests these drugs may have differential effects, probably on the aromatization in the tumor tissue. Further studies are warranted to explore the influence of steroidal and non-steroidal aromatase inhibitors on intratumor aromatase activity and intratumor estrogen concentrations and to correlate these findings to intratumor drug concentrations. The findings that steroidal aromatase inhibitors may have clinical effects in patients progressing on treatment with the non-steroidal aromatase inhibitor aminoglutethimide is challenging, and suggest further studies to evaluate possible benefits of using different novel aromatase inhibitors in concert or sequence.

  • influence of treatment with aminoglutethimide on plasma and red blood cell glutathione status in breast cancer patients
    Cancer Chemotherapy and Pharmacology, 1998
    Co-Authors: Hildegunn Berntsen, Per Eystein Lonning, Dag Clement Johannessen, Dagfinn Ekse, Bjorn Netteland, Rolf K Berge, Asbjorn Svardal
    Abstract:

    Purpose: Elevated cellular glutathione has been associated with resistance to cancer chemotherapy. Treatment with the aromatase inhibitor aminoglutethimide increases the concentration of γ-glutamyl transpeptidase (γ-GT) in breast cancer patients. This enzyme catalyzes the first step in the degradation of extracellular glutathione, and the products formed may act as precursors for intracellular glutathione synthesis. Methods: Plasma and red-blood-cell glutathione levels were determined in 26 patients suffering from advanced breast cancer before and during treatment with aminoglutethimide (n=16) or the steroidal aromatase inhibitors exemestane or Formestane (n=10) and in 5 cancer patients receiving dexamethasone. Results: Pretreatment values for γ-GT in the total patient group (n=31) correlated negatively with the level of reduced (P<0.0001), oxidized (P<0.025), and total glutathione (P<0.005) in plasma. Plasma γ-GT levels increased by a mean value of 249% during treatment with aminoglutethimide. The concentration of reduced and oxidized glutathione in plasma decreased to 42.7% (P<0.0005) and 80.6% (P < 0.005) of their pretreatment levels, respectively. This fall in reduced plasma glutathione correlated negatively with the increase in \(\)-GT (P<0.001). The ratio of oxidized to reduced glutathione increased by 88.9% (P<0.005), and this increase correlated positively with the increase in γ-GT (P<0.005). Treatment with the steroidal aromatase inhibitors (exemestane and Formestane) or dexamethasone did not influence the plasma thiol status. Conclusions: We conclude that aminoglutethimide influences plasma glutathione disposition by mechanisms not related to estrogen suppression or due to glucocorticoids given in concert.

  • effects of treatment with megestrol acetate aminoglutethimide or Formestane on insulin like growth factor igf i and ii igf binding proteins igfbps and igfbp 3 protease status in patients with advanced breast cancer
    The Journal of Clinical Endocrinology and Metabolism, 1996
    Co-Authors: V J Frost, Per Eystein Lonning, S I Helle, J W J Van Der Stappen, Jeffrey M P Holly
    Abstract:

    The effects of treatment with the aromatase inhibitors aminoglutethimide (AG) and Formestane or the synthetic progestin megestrol acetate (MA) on plasma levels of insulin-like growth factor I (IGF-1), IGF-II, IGF-binding proteins (IGFBPs), and IGFBP-3 protease status were investigated in 39 patients suffering from advanced breast cancer. Treatment with AG and MA elevated plasma levels of IGF-I by mean values of 27% (n = 15; P < 0.025) and 81% (n = 7; P < 0.025), respectively, whereas treatment with Formestane had no effect (n = 13). Treatment with AG increased plasma levels of IGFBP-2, as evaluated by Western blotting (P < 0.01). MA caused a significant reduction in IGFBP-3 protease activity (mean reduction, 69%; P < 0.05). These alterations in plasma IGF-I and IGFBP-3 protease activity were reversed 4 weeks after terminating MA therapy (n = 8; P < 0.025). Taken together, 13 of 15 patients had reduced IGFBP-3 protease activity during treatment with MA compared to the control situation (P < 0.0025). Total ...

  • treatment with Formestane alone and in combination with aminoglutethimide in heavily pretreated breast cancer patients clinical and endocrine effects
    European Journal of Cancer, 1996
    Co-Authors: Jurgen Geisler, Dag Clement Johannessen, Gun Anker, Per Eystein Lonning
    Abstract:

    We studied the clinical and endocrine effects of the aromatase inhibitor Formestane (4-hydroxyandrostenedione, 4-OHA) in heavily pretreated breast cancer patients (median number of previous endocrine treatments 2, range 1-4). Of 30 patients eligible for response evaluation, 3 patients (10%) showed a partial response while 11 patients (36.7%) experienced stable disease over a time period of at least 6 months. Plasma levels of oestrone, oestradiol and oestrone sulphate were found suppressed to a mean of 33.9, 35.6 and 24.2% of control values. 4 of 6 patients experienced a further substantial reduction in plasma oestrone sulphate to < 5% of pretreatment values when aminoglutethimide (AG) was added after relapse on 4-OHA monotherapy. Our findings suggest that these aromatase inhibitors may suppress plasma oestrogen levels by a percentage approaching the percentage inhibition of in vivo aromatisation measured by tracer techniques.

Cristina Noberasco - One of the best experts on this subject based on the ideXlab platform.

  • a multicentre randomized pharmacokinetic endocrine and clinical study to evaluate Formestane in breast cancer patients at first relapse endocrine and clinical results
    Annals of Oncology, 1997
    Co-Authors: E Bajetta, N Zilembo, Roberto Buzzoni, Cristina Noberasco, A Martinetti, L Ferrari, Sandro Barni, Giuseppe Schieppati, A Jirillo, M Amichetti
    Abstract:

    Summary 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 pharmaco-kinetics 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.

  • serum markers of bone metastases in postmenopausal breast cancer patients treated with Formestane
    Tumor Biology, 1997
    Co-Authors: A Martinetti, E Bajetta, N Zilembo, Cristina Noberasco, L Ferrari, Ettore Seregni, S Massaron, Lorenza Rimassa, Emilio Bombardieri
    Abstract:

    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 ev

  • activity of Formestane in de novo tamoxifen resistant patients with metastatic breast cancer
    Oncology, 1995
    Co-Authors: Cristina Noberasco, E Bajetta, N Zilembo, C Bartoli, Aldo Bono, A Di Leo, Federico Cappuzzo, Ettore Bichisao
    Abstract:

    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 ≤ 1) were treated with fo

  • Formestane an effective first line endocrine treatment for advanced breast cancer
    Journal of Cancer Research and Clinical Oncology, 1995
    Co-Authors: N Zilembo, E Bajetta, Roberto Buzzoni, Cristina Noberasco, G Vicario, Aldo Bono, A Laffranchi, Giuseppa Biasi, Stella Dolci, Ettore Bichisao
    Abstract:

    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.

  • Formestane as treatment of advanced breast cancer in elderly women
    Tumori, 1994
    Co-Authors: N Zilembo, Roberto Buzzoni, Cristina Noberasco, L Ferrari, G Vicario, A Laffranchi, Stella Dolci, Luigi Celio, E Bajetta
    Abstract:

    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.