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1.
Acta Oncol ; 58(11): 1648-1654, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31345082

RESUMEN

Introduction: Sunitinib is a standard second-line treatment in advanced gastrointestinal stromal tumours (GIST). We aimed to search for predictive factors for grade 3 and 4 toxicity, progression-free survival (PFS) and overall survival (OS) in a GIST reference center patient population, outside clinical trials.Methods: A retrospective analysis was performed of patients treated in two European Comprehensive Cancer Centers between January 2005 and December 2015. Demographic and clinical features, tumour characteristics and biological parameters were investigated. Logistic regression models were used to find factors associated with grade 3 and 4 toxicity. To identify predictive factors for PFS and OS, variables that were statistically significant in univariate analysis were used in the multivariate Cox proportional hazards model.Results: Ninety-one patients were included in this analysis. Age >60 years (HR 5.0, p = .006) and body weight ≤70 kg (HR 4.7, p = .009) were predictive factors for grade 3 and 4 toxicity. When divided into two categories, non-haematological grade 3 and 4 toxicity was predicted by age >60 years (HR 3.8, p = .012) and body weight ≤70 kg (HR 3.3, p = .025) whereas haematological toxicity had no significantly associated predictive factors. The median PFS and OS with sunitinib were 8.8 months and 27.5 months, respectively. The use of imatinib less than six months compared to 6-12 months (HR 0.2, p = .013) and to >12 months (HR 0.3, p = .016) and liver and/or peritoneal metastases (HR 0.1, p < .001, HR 0.2, p = .003 and HR 0.2, p = .004) compared to locally advanced disease only were predictive for longer PFS. High neutrophil (HR 3.1, p = 0.04) and platelet count (HR 2.4, p = .046) predicted a shorter OS. Flexible sunitinib dosing was associated with superior OS (p = .021).Conclusion: In advanced GIST patients treated with sunitinib, older and low-weight patients are at risk for grade 3 and 4 toxicity. Clinical (prior imatinib use and metastases), biological (neutrophil and platelet count) and treatment characteristics independently predict PFS and OS.


Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias Gastrointestinales/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Sunitinib/efectos adversos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Femenino , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/patología , Humanos , Mesilato de Imatinib/uso terapéutico , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Factores de Riesgo , Sunitinib/administración & dosificación , Tasa de Supervivencia , Adulto Joven
2.
Surg Oncol ; 29: 107-112, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31196472

RESUMEN

BACKGROUND: Despite being associated with a very poor prognosis, long-term survivors across all series of Desmoplastic Small Round Cell Tumor (DSRCT) have been reported. AIM OF THE STUDY: To analyze patients 'characteristics associated with a prolonged survival after DSRCT diagnosis. METHODS: All consecutive patients treated for DSRCT in nine French expert centers between 1991 and 2018 were retrospectively analyzed. Patients with a follow-up of less than 2 years were excluded and cure defined as being disease-free at least 5 years. RESULTS: 100 pts were identified (median age 25 years, 89% male). 27 had distant metastases at diagnosis and 80 pts underwent upfront chemotherapy (CT). 71 pts were operated, 20 pts without prior CT). Surgery was macroscopically complete (CC0/1) in 50 pts. Hyperthermic intraperitoneal Chemotherapy (HIPEC) was administered during surgery in 15 pts 54 pts had postoperative CT and 26 pts had postoperative whole abdomino-pelvic RT (WAP-RT). After a median follow-up of 103 months (range 23-311), the median overall survival (OS) was 25 months. The 1- year, 3-year and 5-year OS rates were 90%, 35% and 4% respectively. 5 patients were considered cured after a median disease-free interval of 100 months (range 22-139). Predictive factors of cure were female sex (HR = 0.49, p = 0.014), median PCI<12 (HR = 0.32, p = 0.0004), MD Anderson stage I (HR = 0.25, p < 0.0001), CC0/1 (HR = 0.34, p < 0.0001), and WAP-RT (HR = 0.36, p = 0.00013). HIPEC did not statistically improve survival. CONCLUSION: Cure in DSRCT is possible in 5% of patients and is best achieved combining systemic chemotherapy, complete cytoreductive surgery and WAP-RT. Despite aggressive treatment, recurrence is common and targeted therapies are urgently needed.


Asunto(s)
Quimioterapia del Cáncer por Perfusión Regional/mortalidad , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Tumor Desmoplásico de Células Pequeñas Redondas/mortalidad , Hipertermia Inducida/mortalidad , Neoplasias Peritoneales/mortalidad , Adolescente , Adulto , Niño , Preescolar , Terapia Combinada , Tumor Desmoplásico de Células Pequeñas Redondas/patología , Tumor Desmoplásico de Células Pequeñas Redondas/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
3.
Ann Oncol ; 26(10): 2168-73, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26202596

RESUMEN

BACKGROUND: There is no consensual treatment of locally advanced or metastatic chordomas. PATIENTS AND METHODS: We conducted a multicenter, open-label, uncontrolled phase II trial of sorafenib (800 mg/day). The primary end point was the 9-month progression-free rate according to RECIST 1.1. All patients had documented progressive disease at the time of study entry. RESULTS: Twenty-seven patients were enrolled between May 2011 and January 2014. The median age was 64 (range, 30-86) years. There were 17 men and 10 women. Twelve patients had been previously treated with chemotherapy and molecularly targeted agents. The maximum toxicity grade per patient was grade 3 in 21 cases (77.8%) and grade 4 in 4 cases (14.8%). Sorafenib provided an intent-to-treat best objective response of 1/27 [3.7%; 95% confidence interval (CI) 0.1% to 19.0%], a 9-month progression-free rate of 73.0% (95% CI 46.1-88.0) and a 12-month overall survival rate of 86.5% (95% CI 55.8-96.5). Survival curves were similar in pretreated and not pretreated patients. DISCUSSION: Additional clinical trials further exploring sorafenib as a treatment of locally advanced or metastatic chordomas are warranted.


Asunto(s)
Antineoplásicos/uso terapéutico , Cordoma/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Sarcoma/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Cordoma/mortalidad , Cordoma/secundario , Femenino , Estudios de Seguimiento , Francia , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/uso terapéutico , Pronóstico , Sarcoma/mortalidad , Sarcoma/patología , Sorafenib , Tasa de Supervivencia
4.
Bull Cancer ; 97(6): 723-31, 2010 Jun.
Artículo en Francés | MEDLINE | ID: mdl-20483709

RESUMEN

Since the discovery of the remarkable efficacy of imatinib in the metastatic GIST, several studies advanced our knowledge on the care of this pathology. In the localized GIST, the efficacy of the adjuvant treatment by imatinib was proved, but the duration, the indication and the management in case of relapse after imatinib are not still consensual. The imatinib is also used in neoadjuvant setting to optimize the quality of resection, the main treatment remaining the maximal tumor resection. In metastatic setting, imatinib remains the standard of care first-line treatment. It must be administered until progress or intolerance. Nevertheless, secondary resistance to imatinib is a substantial problem in routine clinical practice; in second line, sunitinib demonstrated its efficacy. Several inhibitors of tyrosine-kinases are ongoing evaluated in all the therapeutic lines. Clearly, a better knowledge of the molecular profile and the pharmacokinetics underlying the resistance to imatinib as well as the development of a new class of broad-spectrum tyrosine-kinase inhibitors may allow in the near future new individualized therapeutic strategies for GIST patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Antineoplásicos/farmacocinética , Benzamidas , Bencenosulfonatos/uso terapéutico , Quimioterapia Adyuvante , Resistencia a Antineoplásicos , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Mesilato de Imatinib , Indoles/uso terapéutico , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Piperazinas/farmacocinética , Piperidinas , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Pirimidinas/farmacocinética , Pirroles/uso terapéutico , Sorafenib , Sunitinib , Tiazoles/uso terapéutico
5.
Cancer Radiother ; 10(4): 185-207, 2006 Jun.
Artículo en Francés | MEDLINE | ID: mdl-16917992

RESUMEN

CONTEXT: The National French Federation of Comprehensive Cancer Centres (FNCLCC) initiated the update of clinical practice guideline for the management of patients with soft tissue sarcoma in collaboration with the French Sarcoma Group (GSF-GETO), specialists from French public universities, general hospitals and private clinics and with the French National Cancer Institute. This work is based on the methodology developed in the "Standards, Options and Recommendations" (SOR) project. OBJECTIVES: To update SOR guidelines for the management of patients with soft tissue sarcoma previously validated in 1995. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGsaccording to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers. RESULTS: This article presents the updated recommendations for radiotherapeutic management. The main recommendations are: 1) irradiation before or after surgical treatment is the standard for soft tissue sarcoma of the extremity and uterine sarcoma; 2) no systematic irradiation should be done in case of retroperitoneal sarcoma.


Asunto(s)
Extremidad Inferior/efectos de la radiación , Neoplasias Retroperitoneales/radioterapia , Sarcoma/radioterapia , Neoplasias de los Tejidos Blandos/radioterapia , Extremidad Superior/efectos de la radiación , Neoplasias Uterinas/radioterapia , Braquiterapia , Femenino , Francia , Humanos , Extremidad Inferior/cirugía , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/radioterapia , Dosificación Radioterapéutica , Radioterapia Ayuvante , Neoplasias Retroperitoneales/cirugía , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Extremidad Superior/cirugía , Neoplasias Uterinas/cirugía
6.
Ann Oncol ; 16(7): 1061-8, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15930042

RESUMEN

BACKGROUND: The optimal dose of TNF-alpha delivered by isolated limb perfusion (ILP) in patients with locally advanced soft tissue sarcoma is still unknown. PATIENTS AND METHODS: Randomised phase II trial comparing hyperthermic ILP (38-40 degrees ) with melphalan and one of the four assigned doses of TNF-alpha: 0.5 mg, 1 mg, 2 mg, and 3/4 mg upper/lower limb. The main end point was objective tumour response on MRI. Secondary end points were histological response, rate of amputation and toxicity. Resection of the remnant tumour was performed 2-3 months after ILP. The sample size was calculated assuming a linear increase of 10% in the objective response rates between each dose level group. RESULTS: One hundred patients (25 per arm) were included. Thirteen per cent of patients had a systemic leakage with a cardiac toxicity in six patients correlated with high doses of TNF-alpha. Objective tumour responses were: 68%, 56%, 72% and 64% in the 0.5 mg, 1 mg, 2 mg and 3 or 4 mg arms, respectively (NS). Sixteen per cent of patients were not operated, 71% had a conservative surgery and 13% were amputated with no difference between the groups. With a median follow-up of 24 months, the 2 year overall and disease-free survival rates (95% CI) were 82% (73% to 89%) and 49% (39% to 59%), respectively. CONCLUSION: At the range of TNF-alpha doses tested, there was no dose effect detected for the objective tumour response, but systemic toxicity was significantly correlated with higher TNF-alpha doses. Efficacy and safety of low-dose TNF-alpha could greatly facilitate ILP procedures in the near future.


Asunto(s)
Quimioterapia del Cáncer por Perfusión Regional , Extremidades , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/administración & dosificación , Adulto , Anciano , Terapia Combinada , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hipertermia Inducida , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Sarcoma/patología , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/terapia , Factor de Necrosis Tumoral alfa/efectos adversos , Factor de Necrosis Tumoral alfa/uso terapéutico
7.
Ann Oncol ; 16(4): 566-78, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15781488

RESUMEN

BACKGROUND: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last 4 years. The objectives of this international consensus meeting were to describe the optimal management procedures for patients with GIST in localized and advanced stages, as well as research issues for the future. MATERIALS AND METHODS: A panel of experts from six specialties, including pathology, molecular biology, imaging, surgery, medical oncology and methodologists for clinical practice guidelines from different European and extra European sarcoma societies were invited to a 2-day workshop. Several questions were selected by the organizing committee prior to the conference. Selected panelists reviewed the current levels of evidence for each point, and presented their conclusions during the meeting. These proposals were discussed, and consensus points were identified and categorized according to the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers and National Comprehensive Cancer Network (NCCN). RESULTS: Thirty-two consensus points were identified, most from categories 2A of the NCCN and B2 of the SOR. Among these, the standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is an optional diagnostic procedure for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. The optimal criteria for tumor response to imatinib remain to be delineated, and should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield Units) on computed tomography and metabolic activity (i.e. reduction of FDG uptake on positron emission tomography). In a substantial proportion of patients, stable disease and even increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. Metastasis resection is an experimental procedure. CONCLUSIONS: Consensus points in clinical management of GIST as well as questions for future clinical trials were identified during this consensus conference on GIST management.


Asunto(s)
Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/cirugía , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Benzamidas , Manejo de la Enfermedad , Europa (Continente) , Tumores del Estroma Gastrointestinal/diagnóstico , Humanos , Mesilato de Imatinib
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