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37 results on '"Massimini, Giorgio"'

2. Selective Oral MEK1/2 Inhibitor Pimasertib in Metastatic Melanoma: Antitumor Activity in a Phase I, Dose-Escalation Trial

Author

Lebbé, Céleste, Italiano, Antoine, Houédé, Nadine, Awada, Ahmad, Aftimos, Philippe, Lesimple, Thierry, Dinulescu, Monica, Schellens, Jan H. M., Leijen, Suzanne, Rottey, Sylvie, Kruse, Vibeke, Kefford, Richard, Raymond, Eric, Faivre, Sandrine, Pages, Celine, Gomez-Roca, Carlos, Schueler, Armin, Goodstal, Samantha, Massimini, Giorgio, and Delord, Jean-Pierre

Published
2021
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3. Digital Display Precision Predictor: the prototype of a global biomarker model to guide treatments with targeted therapy and predict progression-free survival

Author

Lazar, Vladimir, Magidi, Shai, Girard, Nicolas, Savignoni, Alexia, Martini, Jean-François, Massimini, Giorgio, Bresson, Catherine, Berger, Raanan, Onn, Amir, Raynaud, Jacques, Wunder, Fanny, Berindan-Neagoe, Ioana, Sekacheva, Marina, Braña, Irene, Tabernero, Josep, Felip, Enriqueta, Porgador, Angel, Kleinman, Claudia, Batist, Gerald, Solomon, Benjamin, Tsimberidou, Apostolia Maria, Soria, Jean-Charles, Rubin, Eitan, Kurzrock, Razelle, and Schilsky, Richard L.

Published
2021
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4. 763 Initial results from phase I dose escalation trial of CAN1012 in patients with solid tumor malignancies

Author

Yu, Henry, primary, Yao, Herui, additional, Li, Ning, additional, Wang, Shuhang, additional, Curti, Brendan, additional, Massimini, Giorgio, additional, Hu, Ming-Hong, additional, Redmond, William L, additional, Lou, Rongliang, additional, Geng, Wanping, additional, Wang, Sanlong, additional, Zhang, Meiling, additional, Chen, Rongchu, additional, Qin, Baotian, additional, Mao, John, additional, Wang, Shaoshan, additional, and Song, Erwei, additional

Published
2023
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5. Pimasertib versus dacarbazine in patients with unresectable NRAS-mutated cutaneous melanoma: Phase II, randomized, controlled trial with crossover

Author

Lebbe, Céleste, Dutriaux, Caroline, Lesimple, Thierry, Kruit, Wim H, Kerger, Joseph, Thomas, Luc, Guillot, Bernard, De Braud, Filippo De, Garbe, Claus, Grob, Jean Jacques, Loquai, Carmen, Ferraresi, Virginia, Robert, Caroline, Vasey, Paul, Conry, Robert, Isaacs, Richard, Espinosa, Enrique, Schueler, Armin, Massimini, Giorgio, Dreno, Brigitte, Lebbe, Céleste, Dutriaux, Caroline, Lesimple, Thierry, Kruit, Wim H, Kerger, Joseph, Thomas, Luc, Guillot, Bernard, De Braud, Filippo De, Garbe, Claus, Grob, Jean Jacques, Loquai, Carmen, Ferraresi, Virginia, Robert, Caroline, Vasey, Paul, Conry, Robert, Isaacs, Richard, Espinosa, Enrique, Schueler, Armin, Massimini, Giorgio, and Dreno, Brigitte

Abstract

This study investigated the efficacy and safety of pimasertib (MEK1/MEK2 inhibitor) versus dacarbazine (DTIC) in patients with untreated NRAS-mutated melanoma. Phase II, multicenter, open-label trial. Patients with unresectable, stage IIIc/IVM1 NRAS-mutated cutaneous melanoma were randomized 2:1 to pimasertib (60 mg; oral twice-daily) or DTIC (1000 mg/m2; intravenously) on Day 1 of each 21-day cycle. Patients progressing on DTIC could crossover to pimasertib. Primary endpoint: investigator-assessed progression-free survival (PFS); secondary endpoints: overall survival (OS), objective response rate (ORR), quality of life (QoL), and safety. Overall, 194 patients were randomized (pimasertib n = 130, DTIC n = 64), and 191 received treatment (pimasertib n = 130, DTIC n = 61). PFS was significantly improved with pimasertib versus DTIC (median 13 versus 7 weeks, respectively; hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.42–0.83; p = 0.0022). ORR was improved with pimasertib (odds ratio 2.24, 95% CI 1.00–4.98; p = 0.0453). OS was similar between treatments (median 9 versus 11 months, respectively; HR 0.89, 95% CI 0.61–1.30); 64% of patients receiving DTIC crossed over to pimasertib. Serious adverse events (AEs) were more frequent for pimasertib (57%) than DTIC (20%). The most common treatment-emergent AEs were diarrhea (82%) and blood creatine phosphokinase (CPK) increase (68%) for pimasertib, and nausea (41%) and fatigue (38%) for DTIC. Most frequent grade ≥3 AEs were CPK increase (34%) for pimasertib and neutropenia (15%) for DTIC. Mean QoL scores (baseline and last assessment) were similar between treatments. Pimasertib has activity in NRAS-mutated cutaneous melanoma and a safety profile consistent with known toxicities of MEK inhibitors. Trial registration: ClinicalTrials.gov, NCT01693068., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2020

6. Selective Oral MEK1/2 Inhibitor Pimasertib in Metastatic Melanoma: Antitumor Activity in a Phase I, Dose-Escalation Trial

Author

Lebbé, Céleste, primary, Italiano, Antoine, additional, Houédé, Nadine, additional, Awada, Ahmad, additional, Aftimos, Philippe, additional, Lesimple, Thierry, additional, Dinulescu, Monica, additional, Schellens, Jan H. M., additional, Leijen, Suzanne, additional, Rottey, Sylvie, additional, Kruse, Vibeke, additional, Kefford, Richard, additional, Raymond, Eric, additional, Faivre, Sandrine, additional, Pages, Celine, additional, Gomez-Roca, Carlos, additional, Schueler, Armin, additional, Goodstal, Samantha, additional, Massimini, Giorgio, additional, and Delord, Jean-Pierre, additional

Published
2020
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7. Selective Oral MEK1/2 Inhibitor Pimasertib: A Phase I Trial in Patients with Advanced Solid Tumors

Author

Delord, Jean-Pierre, primary, Italiano, Antoine, additional, Awada, Ahmad, additional, Aftimos, Philippe, additional, Houédé, Nadine, additional, Lebbé, Céleste, additional, Pages, Celine, additional, Lesimple, Thierry, additional, Dinulescu, Monica, additional, Schellens, Jan H. M., additional, Leijen, Suzanne, additional, Rottey, Sylvie, additional, Kruse, Vibeke, additional, Kefford, Richard, additional, Faivre, Sandrine, additional, Gomez-Roca, Carlos, additional, Scheuler, Armin, additional, Massimini, Giorgio, additional, and Raymond, Eric, additional

Published
2020
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8. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer

Author

Coombes, R. Charles, Hall, Emma, Gibson, Lorna J., Paridaens, Robert, Delozier, Thierry, Jones, Stephen E., Alvarez, Isabel, Bertelli, Gianfilippo, Ortmann, Olaf, Coates, Alan S., Bajetta, Emilio, Andersen, Jorn, Lonning, Per E., Cocconi, Giorgio, Stewart, Alan, Dodwell, David, Coleman, Robert E., Fallowfield, Lesley J., Mickiewicz, Elizabeth, Stuart, Nick, Snowdown, Claire F., Carpentieri, Marina, Massimini, Giorgio, and Bliss, Judith M.

Subjects
Therapeutics -- Research, Tamoxifen -- Research, Tamoxifen -- Comparative analysis, Clinical trials
Abstract

A double-blind, randomized trial to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The results showed improved disease-free survival as compared with standard treatment.

Published
2004

10. Pimasertib Versus Dacarbazine in Patients With Unresectable NRAS-Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover

Author

Lebbé, Celeste, primary, Dutriaux, Caroline, additional, Lesimple, Thierry, additional, Kruit, Willem, additional, Kerger, Joseph, additional, Thomas, Luc, additional, Guillot, Bernard, additional, de Braud, Filippo, additional, Garbe, Claus, additional, Grob, Jean-Jacques, additional, Loquai, Carmen, additional, Ferraresi, Virginia, additional, Robert, Caroline, additional, Vasey, Paul, additional, Conry, Robert, additional, Isaacs, Richard, additional, Espinosa, Enrique, additional, Schueler, Armin, additional, Massimini, Giorgio, additional, and Dréno, Brigitte, additional

Published
2020
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11. A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease

Author

Fiedler, Walter, Serve, Hubert, Döhner, Hartmut, Schwittay, Michael, Ottmann, Oliver G., O'Farrell, Anne-Marie, Bello, Carlo L., Allred, Randy, Manning, William C., Cherrington, Julie M., Louie, Sharianne G., Hong, Weiru, Brega, Nicoletta M., Massimini, Giorgio, Scigalla, Paul, Berdel, Wolfgang E., and Hossfeld, Dieter K.

Published
2005
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16. Exemestane Is Superior to Megestrol Acetate After Tamoxifen Failure in Postmenopausal Women With Advanced Breast Cancer: Results of a Phase III Randomized Double-Blind Trial

Author

Kaufmann, Manfred, Bajetta, Emilio, Dirix, Luc Yves, Fein, Luis Enrique, Jones, Stephen E., Zilembo, Nicoletta, Dugardyn, Jean-Louis, Nasurdi, Cristina, Mennel, Robert G., Cervek, Jozica, Fowst, Camilla, Polli, Anna, di Salle, Enrico, Arkhipov, Alexei, Piscitelli, Gabriella, Miller, Langdon L., and Massimini, Giorgio

Published
2000

18. Pimasertib, a selective oral MEK1/2 inhibitor: absolute bioavailability, mass balance, elimination route, and metabolite profile in cancer patients

Author

von Richter, Oliver, Massimini, Giorgio, Scheible, Holger, Udvaros, Istvan, and Johne, Andreas

Subjects
Male, Niacinamide, Metabolic Clearance Rate, MAP Kinase Kinase 2, MAP Kinase Kinase 1, Administration, Oral, Biological Availability, Antineoplastic Agents, Feces, Ethanolamines, Neoplasms, Humans, Clinical Trials, Carbon Radioisotopes
Abstract

This trial (NCT: 01713036) investigated the absolute bioavailability, mass balance and metabolite profile of pimasertib in a new design combining these investigations in a single group of patients.Six male patients with pathologically confirmed, locally advanced or metastatic solid tumours were enrolled. Exclusion criteria included Eastern Cooperative Oncology Group performance status1. In Part A of the trial, patients received a 60 mg oral dose of unlabelled pimasertib followed by an intravenous (i.v.) tracer dose of [Following i.v. administration, [Pimasertib showed a favourable pharmacokinetic profile with high absolute bioavailability and a unique metabolic pathway (conjugation with phosphoethanolamine).

Published
2016

21. Pimasertib, a selective oral MEK1/2 inhibitor: absolute bioavailability, mass balance, elimination route, and metabolite profile in cancer patients.

Author

Richter, Oliver, Massimini, Giorgio, Scheible, Holger, Udvaros, Istvan, and Johne, Andreas

Subjects
*BIOAVAILABILITY, *METABOLITE synthesis, *ONCOLOGY, *DRUG administration, *CANCER patients
Abstract

Aim This trial (NCT: 01713036) investigated the absolute bioavailability, mass balance and metabolite profile of pimasertib in a new design combining these investigations in a single group of patients. Methods Six male patients with pathologically confirmed, locally advanced or metastatic solid tumours were enrolled. Exclusion criteria included Eastern Cooperative Oncology Group performance status >1. In Part A of the trial, patients received a 60 mg oral dose of unlabelled pimasertib followed by an intravenous (i.v.) tracer dose of [14C]pimasertib 2 μg (equalling 9 kBq) as a bolus injection, one hour after the oral dose, on Day 1. On Day 8, all patients received 60 mg pimasertib capsules spiked with 2.6 MBq of [14C]pimasertib. Patients received 60 mg oral unlabelled pimasertib twice daily from Day 3 to Day 21 of Part A and in subsequent 21-day cycles in Part B. Results Following i.v. administration, [14C]pimasertib exhibited a geometric mean total body clearance of 45.7 l h−1 (geometric coefficient of variation [geometric CV]: 47.2%) and a volume of distribution of 229 l (geometric CV: 42.0%). Absolute bioavailability was 73%. The majority of the oral [14C] dose (85.1%) was recovered in excreta. Total radioactivity was mainly excreted into urine (52.8%) and faeces (30.7%) with 78.9% of the [14C] dose recovered as metabolites. Two major circulating metabolites were identified in plasma: a carboxylic acid (M445) and a phosphoethanolamine conjugate (M554). The safety profile was in line with the published pimasertib trials. Conclusion Pimasertib showed a favourable pharmacokinetic profile with high absolute bioavailability and a unique metabolic pathway (conjugation with phosphoethanolamine). [ABSTRACT FROM AUTHOR]

Published
2016
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22. A multicenter, randomized, phase Ib/II trial of the oral c-Met inhibitor MSC2156119J as monotherapy versus sorafenib in Asian patients with MET-positive (MET+) advanced hepatocellular carcinoma (HCC) and Child-Pugh Class A liver function.

Author

Qin, Shukui, primary, Cheng, Ann-Lii, additional, Lim, Ho Yeong, additional, Xu, Lianzhe, additional, Bladt, Friedhelm, additional, Johne, Andreas, additional, Li, Cindy, additional, Zheng, Hongxia, additional, and Massimini, Giorgio, additional

Published
2014
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24. Phase I/II multicenter, randomized, open-label trial of the c-Met inhibitor MSC2156119J and gefitinib versus chemotherapy as second-line treatment in patients with MET-positive (MET+), locally advanced, or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor mutation (EGFRm+) and progression on gefitinib.

Author

Wu, Yi-Long, primary, Yang, James Chih-Hsin, additional, Park, Keunchil, additional, Xu, Lianzhe, additional, Bladt, Friedhelm, additional, Johne, Andreas, additional, Li, Peiqi, additional, Zheng, Hongxia, additional, and Massimini, Giorgio, additional

Published
2014
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25. Oral C-Met Inhibitor MSC2156119J as Monotherapy Versus Sorafenib in First-Line Treatment of Asian Patients with Met-Positive Advanced Hepatocellular Carcinoma and Child-Pugh Class a Liver Function: Phase IB/II, Multicenter, Randomized Trial

Author

Qin Shukui, Cheng Ann-Lii, Li Cindy, Massimini Giorgio, Lim Ho Yeong, and Xu Lianzhe

Subjects
Oncology, Sorafenib, medicine.medical_specialty, C-Met Inhibitor MSC2156119J, business.industry, Hematology, medicine.disease, law.invention, First line treatment, Randomized controlled trial, law, Internal medicine, Hepatocellular carcinoma, Medicine, Liver function, business, MET Positive, medicine.drug
Published
2014

26. Durable responses to imatinib in patients with PDGFRB fusion gene–positive and BCR-ABL–negative chronic myeloproliferative disorders

Author

David, Marianna, primary, Cross, Nicholas C. P., additional, Burgstaller, Sonja, additional, Chase, Andrew, additional, Curtis, Claire, additional, Dang, Raymond, additional, Gardembas, Martine, additional, Goldman, John M., additional, Grand, Francis, additional, Hughes, George, additional, Huguet, Francoise, additional, Lavender, Louise, additional, McArthur, Grant A., additional, Mahon, Francois X., additional, Massimini, Giorgio, additional, Melo, Junia, additional, Rousselot, Philippe, additional, Russell-Jones, Robin J., additional, Seymour, John F., additional, Smith, Graeme, additional, Stark, Alastair, additional, Waghorn, Katherine, additional, Nikolova, Zariana, additional, and Apperley, Jane F., additional

Published
2006
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27. Survival advantage from imatinib compared with the combination interferon-α plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials

Author

Roy, Lydia, primary, Guilhot, Joëlle, additional, Krahnke, Tillmann, additional, Guerci-Bresler, Agnès, additional, Druker, Brian J., additional, Larson, Richard A., additional, O'Brien, Steve, additional, So, Charlene, additional, Massimini, Giorgio, additional, and Guilhot, François, additional

Published
2006
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31. Primary hypothyroidism associated with interleukin-2 and interferon alpha-2 therapy of melanoma and renal carcinoma

Author

Scalzo, Silvia, primary, Gengaro, Antonio, additional, Boccoli, Giovanni, additional, Masciulli, Rosalba, additional, Giannella, Gianfranco, additional, Salvo, G., additional, Marolla, Paolo, additional, Carlini, P., additional, Massimini, Giorgio, additional, Holdener, E.E., additional, Testa, Ugo, additional, Calabresi, Federico, additional, and Peschle, Cesare, additional

Published
1990
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32. Durable responses to imatinib in patients with PDGFRBfusion gene–positive and BCR-ABL–negative chronic myeloproliferative disorders

Author

David, Marianna, Cross, Nicholas C.P., Burgstaller, Sonja, Chase, Andrew, Curtis, Claire, Dang, Raymond, Gardembas, Martine, Goldman, John M., Grand, Francis, Hughes, George, Huguet, Francoise, Lavender, Louise, McArthur, Grant A., Mahon, Francois X., Massimini, Giorgio, Melo, Junia, Rousselot, Philippe, Russell-Jones, Robin J., Seymour, John F., Smith, Graeme, Stark, Alastair, Waghorn, Katherine, Nikolova, Zariana, and Apperley, Jane F.

Abstract

Fusion genes derived from the platelet-derived growth factor receptor beta (PDGFRB) or alpha (PDGFRA) play an important role in the pathogenesis of BCR-ABL–negative chronic myeloproliferative disorders (CMPDs). These fusion genes encode constitutively activated receptor tyrosine kinases that can be inhibited by imatinib. Twelve patients with BCR-ABL–negative CMPDs and reciprocal translocations involving PDGFRB received imatinib for a median of 47 months (range, 0.1-60 months). Eleven had prompt responses with normalization of peripheral-blood cell counts and disappearance of eosinophilia; 10 had complete resolution of cytogenetic abnormalities and decrease or disappearance of fusion transcripts as measured by reverse transcriptase–polymerase chain reaction (RT-PCR). Updates were sought from 8 further patients previously described in the literature; prompt responses were described in 7 and persist in 6. Our data show that durable hematologic and cytogenetic responses are achieved with imatinib in patients with PDGFRBfusion–positive, BCR-ABL–negative CMPDs.

Published
2007
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33. Survival advantage from imatinib compared with the combination interferon-a plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials

Author

Roy, Lydia, Guilhot, Joe¨lle, Krahnke, Tillmann, Guerci-Bresler, Agne`s, Druker, Brian J., Larson, Richard A., O'Brien, Steve, So, Charlene, Massimini, Giorgio, and Guilhot, Franc¸ois

Abstract

In the multinational IRIS study comparing imatinib with interferon plus cytarabine (IFN/Ara-C) in patients with newly diagnosed chronic-phase chronic myelogenous leukemia (CP CML), imatinib demonstrated significantly higher rates of complete cytogenetic responses (CCyRs) and improved progression-free survival (PFS). However, because of a high early crossover rate to imatinib, survival benefit was not assessable. Here, we report the result of a study comparing long-term outcome of patients included in 2 prospective randomized trials: 551 patients assigned to imatinib in the IRIS trial from 2000 to 2001 and 325 patients who received the combination IFN/Ara-C in the CML91 trial between 1991 and 1996 before imatinib was available. With a follow-up of 42 months for both groups of patients, estimated CCyR, survival free of transformation, and overall survival were significantly higher with imatinib compared with IFN/Ara-C (P < .001, P = .004, and P < .001, respectively). Improved overall survival was also confirmed within different Sokal prognostic risk groups. Of interest, among all patients who achieved major cytogenetic response or CCyR at 12 months, the survival rate was similar irrespective of their treatment. In conclusion, within the limitation of this historical comparison, there is a survival advantage from first-line therapy with imatinib over IFN/Ara-C.

Published
2006
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34. COMBINED METHOD FOR TREATING HORMONO-DEPENDENT DISORDERS WITH EXEMESTANE

Author

PHARMACIA ITALIA SPA, DI SALLE ENRICO, PISCITELLI GABRIELLA, MASSIMINI GIORGIO, PURANDARE DINESH, DEKONING GANS HENDRIK, and UPJOHN CO

Subjects
A61P5/24, A61K45/06, A61K31/5685
Abstract

A method of preventing and treating estrogen dependent disorders selected from endometriosis, uterine fibroids, dysfunctional uterine bleeding, endometrial hyperplasia, polycistic ovarian disease, fibrocystic breast disease and fibrocystic mastopathy, is disclosed which is comprised of administering to a mammalian patient in need of such treatment an effective amount of aromatase inactivator exemestane, alone or in combination with additional therapeutic agents.

36. Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders.

Author

David M, Cross NC, Burgstaller S, Chase A, Curtis C, Dang R, Gardembas M, Goldman JM, Grand F, Hughes G, Huguet F, Lavender L, McArthur GA, Mahon FX, Massimini G, Melo J, Rousselot P, Russell-Jones RJ, Seymour JF, Smith G, Stark A, Waghorn K, Nikolova Z, and Apperley JF

Subjects
Adult, Aged, Aged, 80 and over, Benzamides, Biomarkers, Tumor blood, Child, Child, Preschool, Drug Evaluation, Eosinophilia etiology, Female, Follow-Up Studies, Humans, Imatinib Mesylate, Infant, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative blood, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative drug therapy, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative genetics, Male, Middle Aged, Myeloproliferative Disorders blood, Myeloproliferative Disorders genetics, Oncogene Proteins, Fusion genetics, RNA, Messenger blood, RNA, Neoplasm blood, Receptor, Platelet-Derived Growth Factor beta genetics, Retrospective Studies, Reverse Transcriptase Polymerase Chain Reaction, Translocation, Genetic, Treatment Outcome, Antineoplastic Agents therapeutic use, Fusion Proteins, bcr-abl blood, Myeloproliferative Disorders drug therapy, Oncogene Proteins, Fusion blood, Piperazines therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Receptor, Platelet-Derived Growth Factor beta blood
Abstract

Fusion genes derived from the platelet-derived growth factor receptor beta (PDGFRB) or alpha (PDGFRA) play an important role in the pathogenesis of BCR-ABL-negative chronic myeloproliferative disorders (CMPDs). These fusion genes encode constitutively activated receptor tyrosine kinases that can be inhibited by imatinib. Twelve patients with BCR-ABL-negative CMPDs and reciprocal translocations involving PDGFRB received imatinib for a median of 47 months (range, 0.1-60 months). Eleven had prompt responses with normalization of peripheral-blood cell counts and disappearance of eosinophilia; 10 had complete resolution of cytogenetic abnormalities and decrease or disappearance of fusion transcripts as measured by reverse transcriptase-polymerase chain reaction (RT-PCR). Updates were sought from 8 further patients previously described in the literature; prompt responses were described in 7 and persist in 6. Our data show that durable hematologic and cytogenetic responses are achieved with imatinib in patients with PDGFRB fusion-positive, BCR-ABL-negative CMPDs.

Published
2007
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37. Bone turnover markers and insulin-like growth factor components in metastatic breast cancer: results from a randomised trial of exemestane vs megestrol acetate.

Author

Martinetti A, Zilembo N, Ferrari L, Massimini G, Polli A, La Torre I, Giovanazzi R, Pozzi P, Bidoli P, De Candis D, Seregni E, Bombardieri E, and Bajetta E

Subjects
Adult, Aged, Aged, 80 and over, Alkaline Phosphatase blood, Breast Neoplasms blood, Collagen Type I, Double-Blind Method, Female, Humans, Insulin-Like Growth Factor Binding Protein 3 blood, Insulin-Like Growth Factor I metabolism, Insulin-Like Growth Factor II metabolism, Middle Aged, Peptide Fragments blood, Peptides, Procollagen blood, Androstadienes therapeutic use, Antineoplastic Agents therapeutic use, Biomarkers, Tumor blood, Bone Resorption metabolism, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Megestrol therapeutic use, Somatomedins metabolism
Abstract

The aim of this randomised study was to compare the effects of progestins and aromatase inactivators on bone remodelling markers and the components of insulin-like growth factor in patients with metastatic breast cancer. Within the framework of a large (769 patients), randomised double-blind clinical trial comparing exemestane (EXE) with megestrol acetate (MA), serum 17 beta-estradiol (E2), estrone (E1), estrone sulphate (E1S), bone alkaline phosphatase (BAP), carboxy-terminal cross-linking telopeptide of type I collagen (ICTP) and the components of insulin-like growth factor (IGF) family (IGF-1, IGF-2 and IGFBP-3) were determined in 53 patients (24 randomised to EXE and 29 ramdomised to MA). After eight weeks of treatment, both ICTP and BAP increased (p < 0.01) in the EXE group, but only ICTP in the MA group (p < 0.03). The 8-week suppression of E2 and E1S was more pronounced in the EXE group (to, respectively, 11.2% and 9.9% of baseline values) than in the MA group (33.1% and 29.7%). IGF-1 increased (p < 0.01) in both groups, but more so in the patients treated with MA. Estrogen levels negatively correlated with ICTP in both groups, but were not related to BAP in either. IGF-1 negatively correlated with estrogens in both groups. The results of this study indicate that anti-aromatase therapy is associated with increased osteoclast activity, and suggest the existence of possible differential effects of different hormonal therapies on bone remodelling markers regardless of the estrogen suppression induced by EXE.

Published
2003

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