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1.
Target Oncol ; 15(5): 613-622, 2020 10.
Article in English | MEDLINE | ID: mdl-33025213

ABSTRACT

BACKGROUND: The cell cycle checkpoint G1/S, dependent on cyclin-dependent kinase (CDK) 4 amplification/overexpression and retinoblastoma phosphorylation, is altered in most anaplastic oligodendrogliomas (AOs). OBJECTIVE: We aimed to evaluate the efficacy of palbociclib, an oral inhibitor of CDK4/6 with proven efficacy in breast cancer, in patients with AO. The primary endpoint was progression-free survival at 6 months. PATIENTS AND METHODS: We conducted a multicenter, open-label, phase II trial evaluating the efficacy and safety of palbociclib in patients with AO who progressed on radiotherapy and chemotherapy with histologically and molecularly confirmed grade 3 oligodendroglioma and conserved retinoblastoma protein (pRb) expression by immunohistochemistry. Patients were treated with palbociclib (125 mg/day) for 3/1 weeks on/off. RESULTS: Overall, 34 patients were enrolled across 10 hospitals in the Spanish Group of Neuro-Oncology (GEINO) study. The study was stopped early owing to the lack of efficacy, with 74% of evaluable patients progressing within 6 months, which was insufficient to consider palbociclib as an active drug in this population. Within the median follow-up of 12 months, the median progression-free survival was 2.8 months [95% confidence interval (CI) 2.6-3.1] and the median overall survival was 32.1 months (95% CI 5.1-59.2). There were no partial or complete responses; only 13 patients (38%) achieved stable disease as the best response. Palbociclib was well tolerated, with neutropenia (grade 3 or higher: 58.8%) and thrombocytopenia (grade 3 or higher: 14.7%) as the most common adverse events (AEs). Both AEs had no significant impact. CONCLUSION: Despite the good tolerance, palbociclib monotherapy did not show favorable efficacy against recurrent AO. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier NCT0253032 (retrospectively registered on 21 August 2015).


Subject(s)
Oligodendroglioma/drug therapy , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyridines/therapeutic use , Retinoblastoma/drug therapy , Adult , Aged , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Oligodendroglioma/pathology , Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyridines/pharmacology , Retinoblastoma/pathology , Treatment Outcome
2.
Ann Nucl Med ; 32(8): 568-572, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30051167

ABSTRACT

Large cell neuroendocrine carcinoma of the lung (LCNEC) is a high-grade, poorly differentiated tumor that typically does not express somatostatin receptors. Thus, it does not benefit from treatment with somatostatin analogs and peptide receptor radionuclide therapy (PRRT). The current study objective was to demonstrate that treatment with PRRT may be a valid option in neuroendocrine carcinomas with high expression of somatostatin receptors. This is a case report of a 58-year-old man who was diagnosed with LCNEC and received chemotherapy treatment with little benefit. Extensive hepatic and bone metastasis was detected on 111In-pentetreotide scintigraphy following high uptake of the radionuclide by the tumors. The patient benefitted from neuroendocrine treatment initially and from lutetium Lu 177 dotatate subsequently. A significant clinical and radiological response was observed, along with an improvement in quality of life. The use of PRRT is a valid alternative to chemotherapy in patients with LCNEC involving the expression of somatostin receptors.


Subject(s)
Lung Neoplasms/radiotherapy , Neuroendocrine Tumors/radiotherapy , Octreotide/analogs & derivatives , Organometallic Compounds/therapeutic use , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Grading , Neuroendocrine Tumors/pathology , Octreotide/therapeutic use , Quality of Life , Treatment Outcome
3.
Urology ; 117: 41-43, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29702156

ABSTRACT

OBJECTIVE: To demonstrate that patients with Xp11.2/TFE3 gene-fusion translocation renal cell carcinoma (RCC), despite having an aggressive course in young adults, could have valid treatment options such as mammalian target of rapamycin (mTOR) inhibitors with good outcomes. Furthermore, to explain possible mechanisms of action of mTOR inhibitors in this type of RCC. MATERIALS AND METHODS: We report a case of a 44-year-old man who has been treated with everolimus for a Xp11.2 translocation/TFE3 gene-fusion RCC after 2 previous failed treatments with tyrosine kinase inhibitor. During the follow-up, we evaluated type and duration of response with everolimus. RESULTS: The patient obtained a long-lasting response of disease of 25 months with everolimus without any symptom. CONCLUSION: We believe that mTOR inhibitors could be a good line option treatment to consider for this type of patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Everolimus/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Translocation, Genetic , Adult , Chromosomes, Human, X , Gene Fusion , Humans , Male , Progression-Free Survival , TOR Serine-Threonine Kinases/antagonists & inhibitors
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