Growth hormone receptor variants and response to pegvisomant in monotherapy or in combination with somatostatin analogs in acromegalic patients: A multicenter study
| Autor: | Maura Arosio, Carlo Martini, Diego Ferone, Marie Lise Jaffrain-Rea, A. Colao, Alessandro Peri, L. De Marinis, Giorgio Arnaldi, Luca Olgiati, Giovanna Mantovani, Salvatore Cannavò, Andrea Lania, Anna Spada, Marcello Filopanti, Sabrina Corbetta, Valentina Gasco, Gabriella Angeletti, F. Bogazzi, Francesca Pigliaru |
|---|---|
| Přispěvatelé: | Filopanti, M, Olgiati, L, Mantovani, G, Corbetta, S, Arosio, M, Gasco, V, De Marinis, L, Martini, C, Bogazzi, F, Cannavò, S, Colao, A, Ferone, Diego, Arnaldi, G, Pigliaru, F, Peri, A, Angeletti, G, Jaffrain Rea, Ml, Lania, Ag, Spada, A. |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
drug safety
Endocrinology Diabetes and Metabolism genotype Clinical Biochemistry Drug Resistance drug response Growth hormone receptor Biochemistry Efficacy Endocrinology molecular pathology single nucleotide polymorphism Receptors Antineoplastic Combined Chemotherapy Protocols genetic variability exon pegvisomant combination chemotherapy Human Growth Hormone adult article Combination chemotherapy Middle Aged growth hormone receptor somatostatin derivative acromegaly controlled study DNA sequence drug efficacy drug tolerability drug withdrawal female gene deletion gene frequency gene location human intermethod comparison lipohypertrophy major clinical study male marker gene monotherapy multicenter study multiplex polymerase chain reaction nucleotide sequence outcome assessment patient compliance prediction priority journal side effect tumor volume Somatostatin Drug hormones hormone substitutes and hormone antagonists medicine.drug Adenoma medicine.medical_specialty Somatotropin Context (language use) somatostatin derivative Dose-Response Relationship Genetic Internal medicine Acromegaly medicine Humans Polymorphism Adverse effect Polymorphism Genetic Dose-Response Relationship Drug business.industry Biochemistry (medical) Adult Cross-Sectional Studies Drug Resistance Neoplasm Female Follow-Up Studies Genotype Growth Hormone-Secreting Pituitary Adenoma Male Receptors Somatotropin Settore MED/13 - ENDOCRINOLOGIA medicine.disease Pegvisomant GH-secreting pituitary adenomas Pharmacogenomics Neoplasm acromegaly business |
| Popis: | Context: The influence of full-length GH receptor (GHR) and exon 3-deleted GHR (d3GHR) on responsiveness to pegvisomant (PEG-V) in acromegalic patients is uncertain. Objective: The aim of the study was to assess the distribution of GHR genotypes in a large series of patients on PEG-V therapy and their influence on treatment efficacy and adverse effects. Design and Setting: A cross-sectional multicenter pharmacogenetic study was conducted in 16 Italian endocrinology centers of major universities and tertiary care hospitals. Patients: The study included 127 acromegalic patients enrolled from 2009 to 2010 not cured by previous surgery, radiotherapy, and long-acting somatostatin (SST) analogs, treated with PEG-V. Intervention and Main Outcome Measure: Sixty-three of 127 patients received combined PEG-V + SST analog therapy. Clinical and hormonal data at diagnosis and before and during PEG-V therapy were inserted in a database. GHR exon 3 deletion and other polymorphisms were genotyped by the coordinator center. Differences in PEG-V dosage required for IGF-I normalization and occurrence of adverse effects between carriers and noncarriers of GHR variants were evaluated. Results: d3GHR variants were not in Hardy-Weinberg equilibrium (P = 0.008). No association of these variants with PEG-V dose required for IGF-I normalization, adverse effects occurrence, and tumor regrowth was found in patients on PEG-V and on PEG-V + SST analog treatment. Similar data were obtained considering the GHR variant rs6180. Conclusions: This study did not confirm a better response of d3GHR to PEG-V treatment in acromegaly. Other studies are needed to determine whether deviation from Hardy-Weinberg equilibrium may indicate an association of d3GHR genotype with poor response to usual treatments. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|