RESUMEN
OBJECTIVE: We have previously shown that epithelial ovarian cancer (EOC) and its treatments have negative effects on long-term quality of life (QoL) and fatigue. The present multicenter study investigated the main menopausal symptoms and gynecological management of EOC survivors (EOCS). METHODS: 166 patients with relapse-free ≥3 years after the end of treatment attended a consultation with a gynecologist, including a questionnaire related to vasomotor symptoms (VMS) and sexuality, a clinical examination, a blood sample and an osteodensitometry. QoL, fatigue, insomnia and mood disorders were measured with validated questionnaires and correlated to VMS. VMS and QoL were assessed according to natural menopause (NM) or surgical menopause (SM). RESULTS: Mean age at the survey was 62 [21-83] years and stage III/IV (48%). Mean delay since the end of treatment was 6 years. Fifty-nine patients (36%) had SM. Half of patients reported VMS. Seventy-two percent of EOCS with SM had VMS compared to 41% with NM (P < .001). VMS were not associated with poor global QoL, fatigue, insomnia or mood disorders. Two-thirds of EOCS reported a decrease in libido. Patients with SM showed a greater decrease in libido than NM (P < .02). Fourteen percent of them had osteoporosis and 50% osteopenia. Among the 85 patients with VMS, 80 did not receive HRT after cancer treatment. At the time of the survey, only 7 (4%) patients were receiving hormone replacement therapy (HRT). CONCLUSIONS: VMS and sexual disorders are frequently reported by EOCS, particularly among patients with SM. Most EOCS with menopausal symptoms could benefit from HRT to improve these symptoms.
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Supervivientes de Cáncer , Carcinoma Epitelial de Ovario/fisiopatología , Menopausia/fisiología , Neoplasias Ováricas/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Epitelial de Ovario/cirugía , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/cirugía , Calidad de Vida , Factores Sociodemográficos , Sistema Vasomotor/fisiopatología , Adulto JovenRESUMEN
OBJECTIVE: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in heavily pretreated patients and as maintenance treatment in patients with newly-diagnosed or recurrent ovarian cancer following a response to platinum-based chemotherapy. We present long-term safety data for niraparib from the ENGOT-OV16/NOVA trial. METHODS: This multicenter, double-blind, randomized, controlled phase III trial evaluated the efficacy and safety of niraparib for the treatment of recurrent ovarian cancer. Patients were randomly assigned 2:1 to receive either once-daily niraparib 300 mg or placebo. Two independent cohorts were enrolled based on germline BRCA mutation status. The primary endpoint was progression-free survival, reported previously. Long-term safety data were from the most recent data cutoff (September 2017). RESULTS: Overall, 367 patients received niraparib 300 mg once daily. Dose reductions due to TEAEs were highest in month 1 (34%) and declined every month thereafter. Incidence of any-grade and grade ≥ 3 hematologic and symptomatic TEAEs was also highest in month 1 and subsequently declined. Incidence of grade ≥ 3 thrombocytopenia decreased from 28% (month 1) to 9% and 5% (months 2 and 3, respectively), with protocol-directed dose interruptions and/or reductions. Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) were reported in 2 and 6 niraparib-treated patients, respectively, and in 1 placebo patient each. Treatment discontinuations due to TEAEs were <5% in each month and time interval measured. CONCLUSION: These data demonstrate the importance of appropriate dose reduction according to toxicity criteria and support the safe long-term use of niraparib for maintenance treatment in patients with recurrent ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01847274.
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Carcinoma Epitelial de Ovario/tratamiento farmacológico , Indazoles/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Piperidinas/administración & dosificación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Indazoles/efectos adversos , Quimioterapia de Mantención/métodos , Persona de Mediana Edad , Piperidinas/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Supervivencia sin ProgresiónRESUMEN
BACKGROUND: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. PATIENTS AND METHODS: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. RESULTS: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. CONCLUSION: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.
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Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias Ováricas/terapia , Espera Vigilante , Adolescente , Adulto , Anciano , Coriocarcinoma/tratamiento farmacológico , Coriocarcinoma/patología , Coriocarcinoma/cirugía , Coriocarcinoma/terapia , Disgerminoma/tratamiento farmacológico , Disgerminoma/patología , Disgerminoma/cirugía , Disgerminoma/terapia , Tumor del Seno Endodérmico/tratamiento farmacológico , Tumor del Seno Endodérmico/patología , Tumor del Seno Endodérmico/cirugía , Tumor del Seno Endodérmico/terapia , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Pronóstico , Estudios Retrospectivos , Teratoma/tratamiento farmacológico , Teratoma/patología , Teratoma/cirugía , Teratoma/terapia , Adulto JovenRESUMEN
BACKGROUND: Few data are available on long-term fatigue (LTF) and quality of life (QoL) among epithelial ovarian cancer survivors (EOCS). In this case-control study, we compared LTF, symptoms and several QoL domains in EOCS relapse-free ≥3 years after first-line treatment and age-matched healthy women. PATIENTS AND METHODS: EOCS were recruited from 25 cooperative GINECO centers in France. Controls were randomly selected from the electoral rolls. All participants completed validated self-reported questionnaires: fatigue (FACIT-F), QoL (FACT-G/O), neurotoxicity (FACT-Ntx), anxiety/depression (HADS), sleep disturbance (ISI), and physical activity (IPAQ). Severe LTF (SLTF) was defined as a FACIT-F score <37/52. Univariate and multivariate logistic regressions were conducted to analyze SLTF and its influencing factors in EOCS. RESULTS: A total of 318 EOCS and 318 controls were included. EOCS were 63-year-old on average, with FIGO stage I/II (50%), III/IV (48%); 99% had received platinum and taxane chemotherapy, with an average 6-year follow-up. There were no differences between the two groups in socio-demographic characteristics and global QoL. EOCS had poorer FACIT-F scores (40 versus 45, P < 0.0001), lower functional well-being scores (18 versus 20, P = 0.0002), poorer FACT-O scores (31 versus 34 P < 0.0001), and poorer FACT-Ntx scores (35 versus 39, P < 0.0001). They also reported more SLTF (26% versus 13%, P = 0.0004), poorer sleep quality (63% versus 47%, P = 0.0003), and more depression (22% versus 13%, P = 0.01). Fewer than 20% of EOCS and controls exercised regularly. In multivariate analyses, EOCS with high levels of depression, neurotoxicity, and sleep disturbance had an increased risk of developing SLTF (P < 0.01). CONCLUSION: Compared with controls, EOCS presented similar QoL but persistent LTF, EOC-related symptoms, neurotoxicity, depression, and sleep disturbance. Depression, neuropathy, and sleep disturbance are the main conditions associated with severe LTF.
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Supervivientes de Cáncer/estadística & datos numéricos , Carcinoma Epitelial de Ovario/epidemiología , Fatiga/epidemiología , Neoplasias Ováricas/epidemiología , Calidad de Vida/psicología , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/epidemiología , Ansiedad/etiología , Carcinoma Epitelial de Ovario/fisiopatología , Carcinoma Epitelial de Ovario/psicología , Carcinoma Epitelial de Ovario/terapia , Estudios de Casos y Controles , Terapia Combinada , Estudios Transversales , Depresión/epidemiología , Depresión/etiología , Fatiga/etiología , Femenino , Francia/epidemiología , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/fisiopatología , Neoplasias Ováricas/psicología , Neoplasias Ováricas/terapia , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Background: Niraparib is a poly(ADP-ribose) polymerase inhibitor approved in the USA and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to treatment-emergent adverse event (TEAE) was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was carried out to identify clinical parameters that predict dose reductions. Patients and methods: All analyses were carried out on the safety population, comprising all patients who received at least one dose of study drug. Patients were analyzed according to the study drug consumed (i.e., as treated). A predictive modeling method (decision trees) was used to identify important variables for predicting the likelihood of developing grade ≥3 thrombocytopenia within 30 days after the first dose of niraparib and determine cut-off points for chosen variables. Results: Following dose modification, 200 mg was the most commonly administered dose in the ENGOT-OV16/NOVA trial. Baseline platelet count and baseline body weight were identified as risk factors for increased incidence of grade ≥3 thrombocytopenia. Patients with a baseline body weight <77 kg or a baseline platelet count <150 000/µl in effect received an average daily dose â¼200 mg (median = 207 mg) due to dose interruption and reduction. Progression-free survival in patients who were dose reduced to either 200 or 100 mg was consistent with that of patients who remained at the 300 mg starting dose. Conclusions: The analysis presented suggests that patients with baseline body weight of <77 kg or baseline platelets of <150 000/µl may benefit from a starting dose of 200 mg/day. ClinicalTrials.gov ID: NCT01847274.
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Indazoles/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Piperidinas/administración & dosificación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Trombocitopenia/epidemiología , Administración Oral , Adulto , Peso Corporal , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Incidencia , Indazoles/efectos adversos , Quimioterapia de Mantención/efectos adversos , Quimioterapia de Mantención/métodos , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Ováricas/sangre , Neoplasias Ováricas/mortalidad , Piperidinas/efectos adversos , Recuento de Plaquetas , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Supervivencia sin Progresión , Estudios Retrospectivos , Factores de Riesgo , Trombocitopenia/sangre , Trombocitopenia/inducido químicamenteRESUMEN
Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma. METHODS: This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety. RESULTS: A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8-6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity. CONCLUSIONS: The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity.
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Aminopiridinas/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma Endometrioide/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Morfolinas/uso terapéutico , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/patología , Quimioterapia Adyuvante , Progresión de la Enfermedad , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: PM01183 is a new compound that blocks active transcription, produces DNA breaks and apoptosis, and affects the inflammatory microenvironment. PM01183 showed strong antitumor activity in preclinical models of cisplatin-resistant epithelial ovarian cancer. PATIENTS AND METHODS: Patients with platinum-resistant/refractory ovarian cancer were included in a two-stage, controlled, randomized (in a second stage), multicenter, phase II study. Primary endpoint was overall response rate (ORR) by RECIST and/or GCIG criteria. The exploratory first stage (n = 22) confirmed the activity of PM01183 as a single agent at 7.0 mg flat dose every 3 weeks (q3wk). The second stage (n = 59) was randomized and controlled with topotecan on days 1-5 q3wk or weekly (every 4 weeks, q4wk). RESULTS: ORR was 23% (95% CI, 13%-37%) for 52 PM01183-treated patients. Median duration of response was 4.6 months (95% CI, 2.5-6.9 months), and 23% (95% CI, 0%-51%) of responses lasted 6 months or more. Ten of the 12 confirmed responses were reported for 33 patients with platinum-resistant disease [ORR = 30% (95% CI, 16%-49%)]; for the 29 patients treated with topotecan in the second stage, no responses were found. Median PFS for all PM01183-treated patients was 4.0 months (95% CI, 2.7-5.6 months), and 5.0 months (95% CI, 2.7-6.9 months) for patients with platinum-resistant disease. Grade 3/4 neutropenia in 85% of patients; febrile neutropenia in 21% and fatigue (grade 3 in 35%) were the principal safety findings for PM01183. CONCLUSION: PM01183 is an active drug in platinum-resistant/refractory ovarian cancer and warrants further development. The highest activity was observed in platinum-resistant disease. Its safety profile indicates the dose should be adjusted to body surface area (mg/m2). TRIAL CODE: EudraCT 2011-002172-16.
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Antineoplásicos/uso terapéutico , Carbolinas/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Platino (Metal)/uso terapéutico , Topotecan/uso terapéutico , Anciano , Femenino , HumanosRESUMEN
BACKGROUND: Lenalidomide has dual antiangiogenic and immunomodulatory properties and confirmed antitumor activity in hematologic malignancies. A phase II study investigating the safety and efficacy of continuous lenalidomide in recurrent ovarian cancer patients was initiated. PATIENTS AND METHODS: Patients with histologically confirmed epithelial ovarian, fallopian tube or primary peritoneal carcinoma, with asymptomatic recurrence 6 months after prior therapy were treated with continuous oral lenalidomide (20 mg/day). The primary end point was to evaluate efficacy according to the rate of disease control at 4 months. Secondary objectives were progression-free survival (PFS) and safety. RESULTS: Most of the 45 patients enrolled and treated had serous histology (78%) and a single line of prior chemotherapy (73%). Median platinum-free interval (PFI) was 11.3 months (range 6.9-56.8). Clinical benefit at 4 months was 38% [95% confidence interval (CI) 23% to 53%]. A 59% disease control rate was reported in patients with a PFI >12 months versus 24% with PFI of 6-12 months (P = 0.023). Four patients had RECIST partial responses and 21 had stable disease. CA125 responses were reported in eight patients, including one complete response. Median PFS was 3.4 months (95% CI 2.4-4.4). Most frequent toxicity was hematologic, notably grade 3-4 neutropenia in 29% of patients, along with fatigue (69%), gastrointestinal toxicity (constipation 53%, abdominal pain 49%, diarrhea 38%, nausea/vomiting 36%) and thrombosis (11%). Eight patients withdrew due to related toxicity. CONCLUSIONS: Lenalidomide shows interesting efficacy in late recurrent ovarian cancer patients. Toxicity was mainly hematologic, gastrointestinal and venous thrombosis. Future studies will evaluate combination of lenalidomide with chemotherapy agents. CLINICALTRIALSGOV: NCT01111903.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Talidomida/análogos & derivados , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno Ca-125/sangre , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Neoplasias de las Trompas Uterinas , Femenino , Humanos , Lenalidomida , Proteínas de la Membrana/sangre , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inducido químicamente , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/sangre , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/sangre , Neoplasias Ováricas/patología , Platino (Metal)/efectos adversos , Talidomida/administración & dosificación , Talidomida/efectos adversosRESUMEN
BACKGROUND: Patients with platinum-sensitive recurrent ovarian cancer have variable prognosis and survival. We extend previous work on prediction of progression-free survival by developing a nomogram to predict overall survival (OS) in these patients treated with platinum-based chemotherapy. PATIENTS AND METHODS: The nomogram was developed using data from the CAELYX in Platinum-Sensitive Ovarian Patients (CALYPSO) trial. Multivariate proportional hazards models were generated based on pre-treatment characteristics to develop a nomogram that classifies patient prognosis based on OS outcome. We also developed two simpler models with fewer variables and conducted model validations in independent datasets from AGO-OVAR Study 2.5 and ICON 4. We compare the performance of the nomogram with the simpler models by examining the differences in the C-statistics and net reclassification index (NRI). RESULTS: The nomogram included six significant predictors: interval from last platinum chemotherapy, performance status, size of the largest tumour, CA-125, haemoglobin and the number of organ sites of metastasis (C-statistic 0.67; 95% confidence interval 0.65-0.69). Among the CALPYSO patients, the median OS for good, intermediate and poor prognosis groups was 56.2, 31.0 and 20.8 months, respectively. When CA-125 was not included in the model, the C-statistics were 0.65 (CALYPSO) and 0.64 (AGO-OVAR 2.5). A simpler model (interval from last platinum chemotherapy, performance status and CA-125) produced a significant decrease of the C-statistic (0.63) and NRI (26.4%, P < 0.0001). CONCLUSIONS: This nomogram with six pre-treatment characteristics improves OS prediction in patients with platinum-sensitive ovarian cancer and is superior to models with fewer prognostic factors or platinum chemotherapy free interval alone. With independent validation, this nomogram could potentially be useful for improved stratification of patients in clinical trials and also for counselling patients.
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Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Platino (Metal)/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ensayos Clínicos como Asunto , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inducido químicamente , Recurrencia Local de Neoplasia/genética , Estadificación de Neoplasias , Nomogramas , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Platino (Metal)/efectos adversos , Platino (Metal)/toxicidad , Pronóstico , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
Everolimus displays antiproliferative effects on cancer cells, yields antiangiogenic activity in established tumours, and shows synergistic activity with paclitaxel in preclinical models. This study assessed the safety and the pharmacokinetic interactions of everolimus and paclitaxel in patients with advanced malignancies. Everolimus was dose escalated from 15 to 30 mg and administered with paclitaxel 80 mg m(-2) on days 1, 8, and 15 every 28 days. Safety was assessed weekly, and dose-limiting toxicity (DLT) was evaluated in cycle 1. A total of 16 patients (median age 54.5 years, range 33-69) were entered; 11 had prior taxane therapy for breast (n=5), ovarian (n=3), and vaginal cancer (n=1) or angiosarcoma (n=2). Grade 3 neutropenia in six patients met the criteria for DLT in two patients receiving everolimus 30 mg weekly. Other drug-related grade 3 toxicities were leucopenia, anaemia, thrombocytopenia, stomatitis, asthenia, and increased liver enzymes. Tumour stabilisation reported in 11 patients exceeded 6 months in 2 patients with breast cancer. Everolimus showed an acceptable safety profile at the dose of 30 mg when combined with weekly paclitaxel 80 mg m(-2), warranting further clinical investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias/metabolismo , Proteínas Quinasas/química , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas , Everolimus , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Paclitaxel/administración & dosificación , Pronóstico , Proteínas Quinasas/metabolismo , Sirolimus/administración & dosificación , Sirolimus/análogos & derivados , Tasa de Supervivencia , Serina-Treonina Quinasas TOR , Distribución Tisular , Resultado del TratamientoRESUMEN
Carcinoma cells lack syndecan-1 expression when they are transiting from an epithelial to a less-differentiated mesenchymal phenotype (epithelial-mesenchymal transition, EMT). Furthermore, a shift of syndecan-1 expression from malignant epithelial cells to reactive stromal cells has also been observed during progression of many carcinomas. Finally, epithelial and/or stromal syndecan-1 expression is of prognostic value in many carcinomas. Because recent results are contradictory in breast carcinomas, we have re-evaluated the prognostic significance of syndecan-1 expression in a cohort of 80 patients with invasive ductal breast carcinomas. The tumours from 80 patients diagnosed with invasive ductal breast carcinomas were used to construct a tissue microarray, which was stained with syndecan-1 by immunohistochemistry. We correlated syndecan-1 expression with clinicopathologic parameters and relapse-free survival (RFS). Exclusive epithelial expression of syndecan-1 is observed in 61.25% of the patients, whereas exclusive stromal expression is observed in 30% of the patients. Only 8.75% of the patients had both stromal and epithelial expressions of syndecan-1. A significant correlation was found between the loss of syndecan-1 epithelial expression and the syndecan-1 stromal expression with high grade of malignancy (P=0.011). The loss of syndecan-1 epithelial expression is correlated with RFS (P=0.001). Using multivariate Cox analysis, loss of epithelial syndecan-1 expression was the only prognostic indicator (P<0.001). We concluded that the loss of syndecan-1 epithelial expression was of strong prognostic value in breast carcinomas.
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Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Sindecano-1/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , PronósticoRESUMEN
The standard treatment for advanced ovarian cancer consist in complete surgical debulking and intravenous platin and taxane based chemotherapy. Despite research efforts, a lot of patients still die from peritoneal carcinomatosis. The aim of our work was to present the state of art about intraperitoneal chemotherapy. Intraperitoneal chemotherapy (IPC): three multi-institutional randomised trials showed that platin based IPC gave better results in term of overall and disease free survival when compared to standard intravenous treatment. Even so, IPC is not yet becoming a new international standard of treatment because a high rate of morbidity. Hyperthermic Intraperitoneal chemotherapy (HIPEC) represents an innovative alternative to IPC. HIPEC is based on a complete surgical debulking without any visible mass and an intraperitoneal chemotherapy with synergy of hyperthermia. Phase II trails have shown its feasibility. Randomised trials are needed to assess its efficiency in improving survival.
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Antineoplásicos/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Peritoneo/efectos de los fármacos , Antineoplásicos/efectos adversos , Ensayos Clínicos Fase II como Asunto , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Hipertermia Inducida , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Compuestos de Platino/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Taxoides/administración & dosificaciónRESUMEN
Lapatinib is an oral, small-molecule, dual kinase inhibitor that targets both HER2 and the EGF receptor. Lapatinib was approved in June 2008 in Europe for the treatment of advanced HER2-positive breast cancer. Promising results in trastuzumab-refractory metastatic breast cancer were obtained from Phase I, II and III studies in combination with chemotherapy. Diarrhea and rash are the most common side-effects and are mostly moderate and treatable. Cardiac toxicity occurs rarely and mostly as an asymptomatic and reversible decrease of left ventricular ejection fraction. Unlike trastuzumab, some data show that lapatinib could cross the blood-brain barrier, with some evidence of activity in treating or preventing brain metastases. Its evaluation is actively ongoing, in combination with trastuzumab and in the adjuvant setting.