RESUMEN
The role of molecular markers in ovarian cancer is still a matter of debate. Protease-activated receptor-1 (PAR1) might be a good marker in some types of malignant tumors and might provide useful information in diagnosis and prognosis. The objective of this study was to evaluate the serum levels of PAR1 in regard to diagnostic, predictive, and prognostic value in epithelial ovarian cancer (EOC) patients. Forty-four EOC patients were enrolled in this study. Serum PAR1 levels were determined by enzyme-linked immunosorbent assay (ELISA) method. Twenty-five age- and sex-matched healthy controls were included in the analysis. The median age of patients was 58 years old, ranging from 22 to 83 years, where most of them had advanced disease (stage III-IV) (n = 40, 91%). The median serum PAR1 values were significantly elevated in patients compared to healthy controls (1.52 ng/ml vs. 1.13 ng/ml) (p = 0.03), whereas any clinical variables including response to chemotherapy did not associate with serum assay (p > 0.05). Progression-free survival (PFS) and overall survival (OS) of patients who did not respond to chemotherapy nor had platinum resistance in relapsed disease were poorer in the analyses. On the other hand, serum PAR1 levels showed no significant adverse effect on either PFS or OS (p = 0.43 and p = 0.49, respectively). These results proved that baseline serum PAR1 levels of patients with EOC were significantly higher than those of healthy people. However, these assays suggested no predictive or prognostic value in this group of patients.
Asunto(s)
Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias Ováricas/diagnóstico , Receptor PAR-1/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Femenino , Humanos , Metaloproteinasa 1 de la Matriz/sangre , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias Glandulares y Epiteliales/sangre , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/sangre , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patologíaRESUMEN
BACKGROUND: Locally advanced breast cancer (LABC) rates are unusually high in developing countries. There is a need for the identification of predictive biomarkers for the selection of patients who could benefit from neoadjuvant chemotherapy (NAC). AIM: As the expression of ALU repeat is increased in cancer and has not been assessed in liquid biopsy of cancer patients, our goal was to assess ALU expression in the blood plasma of LABC patients during NAC. PATIENTS AND METHODS: Plasma samples drawn at baseline and at the end of the fourth cycle of chemotherapy were used to determine the plasma levels of ALU-RNA by quantitative real-time PCR. RESULTS: ALU expression from baseline to the fourth cycle of NAC increased from a median relative level of 1870 to 3370 in the whole group (p = 0.03). The increase in ALU-RNA levels in the course of NAC was more pronounced in premenopausal women and in patients with hormone-positive tumors. In patients with complete response to NAC, baseline ALU expression was higher than that in those with partial response. CONCLUSION: This exploratory study provides evidence that plasma ALU-RNA levels are modulated by the menopausal status and hormone receptor status of breast cancer patients and pre-therapeutic ALU-RNA levels might be useful in predicting the response to chemotherapy in a neoadjuvant setting.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Terapia Neoadyuvante , ARN/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
PURPOSE: To determine the time elapsed between the first notification of the disease and the access to the diagnosis and treatment modalities and the associated factors in female patients with breast cancer in Turkey. METHODS: Data was acquired from a questionnaire involving 535 patients who applied to 14 various oncology clinics in Turkey between 1st and 28th of February 2010. Analyses were performed by the participating clinics and were divided into 3 groups: centers located in metropolitan areas formed group 1 (n=161), those located in Marmara and central Anatolia region formed group 2 (n=189), and centers located in Karadeniz and East-Southeast Anatolia region formed group 3 (n=185). The groups of these centers were formed according to the socioeconomic development of the provinces. RESULTS: The median patient age was 48 years, 56.1% of patients were less than 50 years of age. Eighty-five percent of the patients detected a mass in their breast by self examination and 27% of the patients older than 50 years never had breast imaging until the definite diagnosis was established. The median time elapsed between disease noticed by the patient and application to a health care center was 10 days, between application and biopsy 19 days, between biopsy and surgery 10 days, and between surgery and systemic therapy 31 days. The median time elapsed between patients applying for surgery in groups 1 and 2 centers was 11 and 21 days, respectively (p=0.01). The median time elapsed between biopsy and surgery in groups 1,2 and 3 centers was 14,1.5, and 12 days, respectively (p<0.05). CONCLUSION: A high level of awareness regarding breast cancer in our country is related with the time that is defined as 10 days between disease recognition and medical application. The time elapsed between the application and biopsy, surgery and systemic therapy was longer compared with the corresponding figures in developed countries.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Factores Socioeconómicos , Encuestas y Cuestionarios , Tasa de Supervivencia , TurquíaRESUMEN
Detection of residual tumor cells in the circulation can provide prognostic as well as therapeutic information and help in identifying patients at high risk for developing metastases. Maspin and mammaglobin are two molecules that are specifically associated with breast cancer. We looked for mammaglobin and maspin transcripts in the peripheral blood of patients with breast cancer and evaluated their utility as a marker of the response to therapy. Maspin and mammaglobin transcripts were analyzed in 85 breast-cancer patients by nested RT-PCR, prior to and after treatment. Before therapy, 10 patients were found positive for mammaglobin and 20 patients were positive for maspin. In four patients, both transcripts were detected. Immediately following treatment, only one patient was still positive for mammaglobin while maspin transcripts persisted in three patients. Disease progression was observed mainly in patients in whom maspin transcripts were not detectable. Molecular detection of circulating tumor cells during therapy based on analysis for mammaglobin and maspin transcripts is an easy and practical method that can be applied to follow-up patients. We suggest that detection of mammaglobin mRNA is useful to determine the effect of therapy while maspin transcripts may indicate more aggressive disease.
Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias de la Mama/terapia , Proteínas de Neoplasias/genética , ARN Mensajero/sangre , ARN Neoplásico/sangre , Serpinas/genética , Uteroglobina/genética , Adulto , Biomarcadores de Tumor/genética , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Femenino , Humanos , Mamoglobina A , Persona de Mediana Edad , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Pronóstico , Transcripción GenéticaRESUMEN
BACKGROUND: Triple-negative breast cancer is estimated to account for 15%-20% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular factors in patients with triple-negative breast cancer. PATIENTS AND METHODS: Tumor specimens from 109 patients with receptor-negative (estrogen receptor and progesterone receptor) breast cancer were analyzed for mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR) and phosphoinositol-3-kinase (PI3K) expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables, was investigated. RESULTS: Fifteen (13.8%), 38 (34.9%) and 33 patients (30.3%) had positive staining for EGFR, MAPK and PI3K, respectively. MAPK was associated with anthracycline resistance (P = 0.008) and lower MAPK score was significantly associated with shorter disease-free survival (P = 0.029). Survival following relapse was significantly worse for those with a higher MAPK score (P = 0.03). CONCLUSION: MAPK is a significant prognostic and predictive factor in patients with triple-negative breast cancer. Furthermore, the level of staining among those with a positive MAPK expression may play a prognostic role at different stages of relapse. Further translational research is required to elucidate molecular mechanisms of tumor proliferation in this subset of patients.
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Antraciclinas/farmacología , Antibióticos Antineoplásicos/farmacología , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/enzimología , Resistencia a Antineoplásicos , Proteínas Quinasas Activadas por Mitógenos/análisis , Recurrencia Local de Neoplasia/enzimología , Adulto , Anciano , Antraciclinas/uso terapéutico , Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Mama/química , Receptores ErbB/análisis , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Recurrencia Local de Neoplasia/química , Oportunidad Relativa , Fosfatidilinositol 3-Quinasas/análisis , Pronóstico , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Regulación hacia ArribaRESUMEN
AIMS: To evaluate the role of postmastectomy radiotherapy (PMRT) in patients with pT3-T4N0M0 breast cancer. METHODS: 156 patients with T3-T4N0M0 breast cancer were retrospectively analyzed. RESULTS: Locoregional recurrences were seen in 17 of 156 patients with a median time for development of 27 months (5.7-248.7 months). Two of 9 patients who were not treated with post-operative radiation therapy had locoregional recurrence as compared with 16 of 147 patients receiving radiotherapy. In multivariate analysis, presence of locoregional recurrence was the only significant prognostic factor for overall survival (18% vs. 86%, p<0.001, RR=9.05). The patients with a median number of dissected lymph nodes >or=10 had a significantly better locoregional disease free survival rate as compared with patients with dissected lymph nodes <10 (90% vs. 78%, p=0.04). Chest wall recurrences were clearly higher in patients without chest wall RT since 5 of 49 patients without RT had recurrences in the chest wall region while only 4 of 107 who received chest wall RT had recurrence. However receiving RT to peripherical lymphatic regions had no additional effect on reducing recurrences in these regions (5% vs. 4%). CONCLUSIONS: Due to the lack of phase III randomized trials directly addressing the role of postmastectomy radiotherapy in these stages, our series suggest that postmastectomy radiotherapy to the ipsilateral chest wall is recommended for patients with PT3N0 and T4N0 breast cancer. The need for irradiating axillary or supraclavicular region shall be neglected in patients who undergo sufficient axillary sampling.
Asunto(s)
Neoplasias de la Mama/radioterapia , Radioterapia Adyuvante , Adulto , Anciano , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Distribución de Chi-Cuadrado , Terapia Combinada , Femenino , Humanos , Mastectomía , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Periodo Posoperatorio , Pronóstico , Modelos de Riesgos Proporcionales , Dosificación Radioterapéutica , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The association between glutathione S-transferase pi (GSTpi) and other clinicopathological parameters, response to chemotherapy and clinical outcome were investigated in chemotherapy naive epithelial ovarian cancer patients. Paraffin-embedded material from 55 patients were used for immunohistochemical analysis. All patients had received six cycles of cisplatinum-based chemotherapy and 41 of them were revalued by laparotomy. Pre- and post-chemotherapy GSTpi staining were detected in the cancer tissues of 18/55 (32.7%) and 5/14 (35.7%) patients, respectively. GSTpi expression was not associated with other clinicopathologic parameters. Of 17 patients with postoperative measurable residual disease clinical response was observed in 4/7 of GSTpi positive and in 9/10 GSTpi negative patients (p = 0.25). Pathologic complete response (pCR) was achieved in 5/8 of GSTpi positive and 11/22 of GSTpi negative cases (p = 0.69). There was no significant difference in overall survival and progression-free survival (PFS) according to initial GSTpi status. However the PFS of the five patients (median 22 +/- 5.9 months) who had postchemotherapy positive GSTpi was significantly shorter than the nine patients (10.0 +/- 2.19 months) who had negative GSTpi (p = 0.006). This difference was not observed in overall survival. These results suggest that initial immunohistochemical staining of GSTpi does not aid in the prediction of pCR and clinical outcome in patients with epithelial ovarian cancer. Nonetheless investigation of GSTpi expression after chemotherapy needs further evaluation.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Glutatión Transferasa/metabolismo , Isoenzimas/metabolismo , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/mortalidad , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/patología , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/mortalidad , Adenocarcinoma Papilar/patología , Adulto , Anciano , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/patología , Estudios de Casos y Controles , Supervivencia sin Enfermedad , Femenino , Gutatión-S-Transferasa pi , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neoplasias Ováricas/patología , Adhesión en Parafina , Valor Predictivo de las Pruebas , Pronóstico , Análisis de Supervivencia , Turquía/epidemiologíaRESUMEN
OBJECTIVES: Overexpression of the bcl-2 gene as a result of the t(14,18) translocation leads to neoplastic transformation by suppressing apoptosis. However, apoptotic cell death in response to chemotherapy has not been investigated. This study was planned with the aim to investigate the association between bcl-2 gene rearrangements and apoptotic changes during chemotherapy in patients with non-Hodgkin's lymphoma. DESIGN AND METHODS: Lymphocytes from 33 patients were collected before and during chemotherapy. Bcl-2 gene rearrangements were investigated by PCR. Apoptotic cell death was analyzed by enzyme immunoassay. RESULTS: In 24 cases, mbr gene rearrangements were detected. Apoptosis was successfully induced by chemotherapy in 48% of patients. Two characteristic, clearly distinguishable apoptotic response patterns with transient peaks either following the first or the third course were observed. It was found that apoptosis rates measured after the first course exactly reflect the final response. No correlation was found between bcl-2 gene rearrangements and apoptosis. CONCLUSIONS: Apoptotic cell death rates show transient changes during chemotherapy. Because the midterm response can be misleading, the apoptotic response should be evaluated following the first course of chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/efectos de los fármacos , Reordenamiento Génico/efectos de los fármacos , Genes bcl-2/efectos de los fármacos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Ciclofosfamida/uso terapéutico , Epirrubicina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/sangre , Translocación Genética , Vincristina/uso terapéuticoRESUMEN
A 28-year-old female patient with a recent history of breast carcinoma was referred to our clinic with generalized necrotic skin eruptions and severe mucosal erosions, which developed right after the completion of cranial radiotherapy for brain metastases. She had been receiving prophylactic diphenylhydantoin treatment 100 mg three times daily during radiation therapy. The extensive involvement of the oral mucosa with conjunctivitis and synechiae of the eyelids, facial swelling, and extension of the rash over the trunk and shoulders with bullous detachment of less than 10% of the total body surface strongly suggested Stevens-Johnson syndrome caused by phenytoin treatment in our patient. There has been conflicting evidence on the role of radiotherapy in the increased risk of severe drug reactions. Although various authors have emphasized the augmented rate of severe mucocutaneous reactions caused by anticonvulsants given during radiotherapy and suggested discontinuing the prophylactic use of such drugs in patients with no history of seizures, others have argued in favor of prophylactic anticonvulsants. Given the high risk of seizures, reaching 20% in patients with brain tumors, and the low incidence of drug reactions, the suggestion of refraining from prophylactic anticonvulsants in the setting of primary or metastatic brain tumors is controversial.
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Anticonvulsivantes/efectos adversos , Neoplasias Encefálicas/radioterapia , Irradiación Craneana , Fenitoína/efectos adversos , Síndrome de Stevens-Johnson/etiología , Adulto , Anticonvulsivantes/uso terapéutico , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/secundario , Carcinoma Ductal de Mama/terapia , Femenino , Humanos , Fenitoína/uso terapéuticoRESUMEN
The authors have analyzed, on the one hand, the prognostic impact of microvessel density (MVD) and p53 protein expression in patients with breast cancer, and on the other hand, the correlation between the microvascular pattern and the p53 protein expression. Tumors from 120 patients whose paraffin-embedded tissue blocks were available were analyzed using the immunohistochemical method. MVD and p53 protein expression were correlated with histologic grade and tumor size, respectively. The patients with highly vascularized tumor (high MVD) had decreased overall survival (p = 0.04), whereas overexpressed p53 patients did not. In multivariate analysis, axillary lymph node status (p = 0.007), tumor size (p = 0.01), and MVD (p = 0.02) showed important prognostic influence on overall survival. When the simultaneous influence of MVD and p53 protein expression on survival were analyzed, no interrelationship was detected. The results demonstrate the prognostic impact of MVD on overall survival in breast cancer and no association between MVD and p53 protein expression.
Asunto(s)
Neoplasias de la Mama , Neovascularización Patológica , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Análisis de SupervivenciaRESUMEN
The aim of this study is to assess the clinical usefulness of serum assays of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CYFRA 21.1 in the diagnosis of squamous cell lung cancer. Sixty patients with squamous cell, and twenty-four patients with nonsquamous cell histology of nonsmall cell lung cancer were enrolled in this study. Serum CEA, SCC, and CYFRA 21.1 levels were obtained by commercially available kits. Upper cutoff levels were 10 ng/ml, 3.5 ng/ml, and 3.5 ng/ml, respectively. In squamous cell lung cancer, percentages and 95% confidence interval (CI) of the patients with elevated levels were as follows: for CEA 23.3% (13-36), for SCC 20.0% (10-32), and for CYFRA 21.1 85.0% (73-93). The positivity rate of CYFRA 21.1 was more significant than CEA and SCC in both squamous and nonsquamous cell lung cancer. None of the markers were significant in differentiating squamous/nonsquamous histology. Only tumor marker CEA was significantly elevated in metastatic squamous cell lung cancer (p=0.004). A novel tumor marker CYFRA 21.1 can be used as a reliable tumor marker in diagnosing squamous cell lung cancer. In addition, CEA has an important role in determining metastatic disease.
Asunto(s)
Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Antígeno Carcinoembrionario/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Serpinas , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Intervalos de Confianza , Femenino , Humanos , Queratina-19 , Queratinas , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reproducibilidad de los Resultados , FumarRESUMEN
Thirteen patients with malignant mixed mullerian tumor of the female genital tract, treated and followed in our clinic from 1989 to 1999 were retrospectively evaluated. Seven patients (53.8%) with advanced disease or postoperative residual tumor were treated with adjuvant chemotherapy. The median age at diagnosis was 64 years (range: 26-79). All patients underwent primary surgical cytoreduction. Tumors were localized to the endometrium in five (62.5%), to the ovaries in two (25%) and to the fallopian tube in one (12.5%) patient. One patient with endometrial carcinosarcoma had a simultaneous second primary ovarian epithelial carcinoma. Two patients (25%) had a heterologous sarcomatous component. Myometrial involvement included less than half the thickness in one patient, while there was no myometrial invasion encountered in two patients. Five patients (38.5%) had more than 50% of the myometrium invaded. Two patients received additional radiotherapy. Six patients received cisplatinum-based chemotherapy (4 had doxorubicin including combinations), while one patient was treated with a doxorubicin+ifosphamide combination. Five patients (71.4%) had a complete response (CR) to chemotherapy. Response duration in patients with a CR was +13, +67, +10, +14 and +2 months, respectively. After a median follow-up period of 20 months (3-115 months), six patients have died, five are being followed-up with no evidence of disease, one is alive with metastatic disease and one patient is under treatment. Malignant mixed mullerian tumor of the female genital tract is highly responsive to multimodality treatment strategies. Further prospective studies are required to identify distinct prognostic groups that may benefit from various treatment modalities.
Asunto(s)
Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Tumor Mulleriano Mixto/tratamiento farmacológico , Adolescente , Adulto , Anciano , Terapia Combinada , Femenino , Neoplasias de los Genitales Femeninos/radioterapia , Humanos , Persona de Mediana Edad , Tumor Mulleriano Mixto/radioterapiaRESUMEN
UNLABELLED: The aim of this study was to evaluate the role of serum CA125 levels and computerized tomography (CT) scans in predicting pathologic response of intraperitoneal chemotherapy in patients with ovarian cancer. We prospectively analyzed serum CA125 levels and abdominopelvic CT scans obtained after the completion of intraperitoneal chemotherapy in 52 patients with ovarian cancer and compared the results with subsequent laparotomic findings, which served as the gold standard for statistical analysis. Laparatomy revealed either microscopic or macroscopic residual disease in 20 patients, while 32 patients were completely tumor-free. CA125 levels correlated significantly with laparotomic findings (p=0.003, u=1405). Median CA125 values in patients with residual tumors and in tumor-free patients following intraperitoneal chemotherapy were 14.6 (1-775) and 7.2 (1-37) U/ml, respectively. Although CT-imaging and CA 125 levels had a high specificity (100% and 96.9%, respectively), they showed a low sensitivity rate (50% and 40%, respectively). Similarly, despite high positive predictive values (100% and 88.9%, respectively), the negative predictive values were 76.2% and 72.1%, respectively. CONCLUSION: Although highly specific, CT scans and CA125 levels do not accurately indicate the presence of disease. Due to a high false-negative rate, a normal CT scan or a normal CA125 value is not sufficient to replace a laparotomy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno Ca-125/sangre , Cistadenocarcinoma Papilar/diagnóstico , Neoplasias Ováricas/diagnóstico , Tomografía Computarizada por Rayos X , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia Adyuvante , Cistadenocarcinoma Papilar/diagnóstico por imagen , Cistadenocarcinoma Papilar/tratamiento farmacológico , Cistadenocarcinoma Papilar/inmunología , Cistadenocarcinoma Papilar/cirugía , Femenino , Humanos , Infusiones Parenterales , Laparotomía , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/cirugía , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Twenty-one chemotherapy naive ovarian cancer patients with stage III and minimal residual tumor were treated with cisplatin 75 mg/m2 and mitoxantrone 15 mg/m2 (1st day) by intraperitoneal (i.p.) route and ifosfamide 4 g/m2 (15th day) by i.v. route every 4 weeks for a total of 6 cycles. Pathologic complete response (pCR) was achieved in 9/20 (45%, 95% Confidence Interval - CI - 23-68) of the patients. The median progression free interval (PFI) of the patients with pCR was 45 (range: 18-70) months. For patients with residual tumor <1 cm (n: 11); pCR was 82% and could be achieved only in this subgroup of patients. The cumulative (PFI) and overall survival rate of all patients at 3 years were 40% and 52%, respectively. The median PFI was found to be significantly different between the patients with residual tumor <1 cm (48 months, 95% CI 42-54) and 1-2 cm (9 months, 95% CI 1-16) p<0.001. Main toxicities were emesis and abdominal pain which occurred in 53% and 65% of the courses, respectively. This combination seems to be an effective and feasible approach to previously untreated ovarian cancer patients with minimal tumor burden.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cisplatino/administración & dosificación , Estudios de Factibilidad , Femenino , Humanos , Ifosfamida/administración & dosificación , Infusiones Intravenosas , Inyecciones Intraperitoneales , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Análisis de SupervivenciaRESUMEN
Catheter complications associated with intraperitoneal chemotherapy were evaluated in 171 patients (pts) with primary intra-abdominal malignancies. In 96 pts and 488 courses, single-use catheters (SUC) (3/G 14 Braun) were used between years 1990-1993. In 75 pts and 283 courses a semi-permanent subcutaneous implantable port and catheter system (SIPC) (T 2035/460 mm-F 14-76 Braun) was used between years 1993-1996. Cisplatin (60-75 mg/sqm), 5-fluorouracil (600 mg/sqm), calcium folinate (150 mg), etoposide (180 mg/sqm), mitoxantrone (12-15 mg/sqm) were given in various combinations and periods to patients with ovarian carcinoma (106 pts), gastrointestinal carcinoma (43 pts), hepatocellular carcinoma (17 pts) and mesothelioma (5 pts). The incidence of patients with complications was significantly higher in SUC (45%) than SIPC (23%) (p=0.001). Colon puncture (8.8%, p<0.0001) and subcutaneous leakage (3.7%, p<0.01) rate of the courses were significantly higher in SUC. Pain related to catheter complications (6%, p<0,0002), local infection (1.4%, p=0.02) and obstruction (1.4%, p=0.02) were significantly higher in SIPC. The most important local complications were intra-abdominal fibrosis and adhesions that were surgically documented in 90% of the ovarian cancer patients, and were more severe in patients with the SIPC system. The complication rate and the complication type of these two catheters were found to be significantly different in this retrospective analysis; in order to determine the real complication rate, safety, efficacy and overall acceptability of the catheters, a randomised trial is needed.
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Neoplasias Abdominales/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Catéteres de Permanencia/efectos adversos , Inyecciones Intraperitoneales/efectos adversos , Femenino , Fibrosis/etiología , Humanos , Infecciones/etiología , Dolor/etiología , Estudios Retrospectivos , Adherencias Tisulares/etiologíaRESUMEN
The efficacy of a combination of cyclophosphamide and cisplatin in patients with metastatic and recurrent carcinoma of the cervix, was tested. Thirty patients were included in the study. Initially, 27 patients (90%) had received pelvic radiation and intracavitary boost and one patient was additionally given paraaortic radiation. Cisplatin was given at 75 mg/m2 followed by cyclophosphamide at 750 mg/m2 on day 1 with three weekly intervals for a maximum of six cycles. All patients received a median of four cycles of chemotherapy. The overall response rate for all eligible patients was 20% (continuous CR: 1, CR: 1, PR: 4 patients). Overall response rate and progressive response in patients with relapse within the previous radiation field were 9.5% and 66.7%, respectively; while for patients who had recurrent disease outside any irradiated area both were 44.4%. Eighteen patients (60%) had early withdrawal from the planned schedule, which was due to patient incompliance in seven patients (23.3%), disease progression in ten (33.3%) and early death after the first cycle in one patient (3.3%). Anemia was the most frequent toxicity, necessiating 24 transfusions in nine patients (30%). WHO grade 3 and 4 toxicity were anemia: 13 (43.3%), leucopenia: one (3.3%), thrombocytopenia: two (6.6%), renal: one, emesis: nine (30.0%) patients. The median survival duration for all eligible patients was 11 months. Univariate analysis revealed that progressive response to chemotherapy was the only prognostic factor for survival (7.1 vs 16.8 months, p = 0.003). The combination of cisplatin and cyclophosphamide did not appear to be more active than single agent cisplatin in this patient group with a relatively poor prognosis. Further studies are required to determine a better therapeutic approach for patients with relapsed carcinoma of the cervix.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cisplatino/efectos adversos , Ciclofosfamida/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Biopsia con Aguja , Carcinoma Adenoescamoso/tratamiento farmacológico , Carcinoma Adenoescamoso/mortalidad , Carcinoma Adenoescamoso/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Ciclofosfamida/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Probabilidad , Estudios Prospectivos , Medición de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
A phase II trial was conducted to further explore the potential of salvage intraperitoneal (IP) cisplatin-based therapy in patients with residual ovarian cancer. Twenty-five patients were treated with a regimen of cisplatin (75 mg/m2) and mitoxantrone (15 mg/m2) delivered IP every three weeks for a maximum of six cycles. Ten patients achieved a pathologically complete response (pCR) and six were clinically stable without evidence of disease. After a median follow-up of 18 months, the median progression-free survival (PFS) was 16 months (95% confidence interval-CI-3-29%). The actuarial PFS at 24 months was 36% (95% CI 13-59). Overall eight out of 25 patients (32%) had an IP relapse and thus were considered as local treatment failures. The major toxic side effects were nausea, vomiting, abdominal pain and renal toxicity. Future trials exploring IP delivery of these drugs should attempt to optimize drug dose and schedule and subset analysis of clinical studies should help in identifying patients who are particularly sensitive to this therapeutic approach.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cisplatino/administración & dosificación , Mitoxantrona/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Neoplasia Residual , Cavidad Peritoneal , Terapia RecuperativaRESUMEN
OBJECTIVE: Patients with stage I ovarian cancer show a high incidence of recurrent disease ranging from 30% to 50%, which may be associated with a shortened survival. Therefore, a subset of early-stage patients with poor prognostic factors who are most likely to present with recurrent disease in the next few years may benefit from adjuvant treatment. PATIENTS AND METHOD: In this pilot study, we evaluated the efficacy of combination chemotherapy including intraperitoneal mitoxantrone (12 mg/ml) and cisplatinum (75 mg/ml) on day 1, in addition to intravenous ifosfamide (4000 mg/m2) given on day 15 with mesna protection. Thirteen patients with a median age of 44 years were included in the study. RESULTS: Following a median of 5 cycles of chemotherapy, 12 patients had a complete response (92.3%), while one patient had progressive disease. At the latest follow-up, ten patients were alive with no evidence of disease, two patients had died and one patient was lost to follow-up. Overall and progression-free survival rates at eight years were 82.5+/-11.3% and 83.9+/-10.5%, respectively. Excluding grade 3 and 4 abdominal pain in three (23.1%) patients, there were no serious complications associated with this combination. Dose delay not longer than one week was observed in 3 cycles (5.6%). Port-related complications observed in three patients were colonic perforation, hematoma and leakage. CONCLUSION: This combination has moderate efficacy and tolerable toxicity. However, further studies are required to make definite conclusions regarding the efficacy of this combination in the adjuvant setting in patients with high-risk early stage ovarian carcinoma.
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Adenocarcinoma de Células Claras/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Endometrioide/tratamiento farmacológico , Cistadenocarcinoma Seroso/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adenocarcinoma de Células Claras/patología , Adulto , Anciano , Carcinoma Endometrioide/patología , Cisplatino/administración & dosificación , Cistadenocarcinoma Seroso/patología , Tolerancia a Medicamentos , Estudios de Factibilidad , Femenino , Humanos , Ifosfamida/administración & dosificación , Infusiones Intravenosas , Inyecciones Intraperitoneales , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Análisis de SupervivenciaRESUMEN
BACKGROUND: The aim of this explorative phase II study was to evaluate the activity and safety of lapatinib in combination with intravenous vinorelbine in women with HER2 positive metastatic or recurrent breast cancer. METHODS: Twenty-nine patients were enrolled. The primary objectives were response and clinical benefit (CB) rates, secondary objectives were toxicity, response duration and progression free survival. Patients received 1250 mg oral lapatinib continuously once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS: Although 25 patients were evaluable for response, according to intend to treat analysis of 28 patients; 14% had confirmed partial response (PR) and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3 extra-hematologic toxicities. CONCLUSION: The results of this trial provide evidence to further investigate the potential of this combination for patients unsuitable for trastuzumab or who become refractory to trastuzumab.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/química , Supervivencia sin Enfermedad , Femenino , Humanos , Análisis de Intención de Tratar , Lapatinib , Persona de Mediana Edad , Metástasis de la Neoplasia , Quinazolinas/administración & dosificación , Receptor ErbB-2/análisis , Factores de Tiempo , Turquía , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
OBJECTIVES: Gemcitabine and carboplatin each have demonstrated effectiveness without increased neurotoxicity in pretreated patients with ovarian cancer. We evaluated the efficacy and safety of gemcitabine plus carboplatin in patients with recurrent ovarian cancer in a multicenter phase II study. METHODS: Women with histologically proven measurable or evaluable epithelial ovarian cancer (any FIGO) who relapsed > or =6 months after discontinuation of first-line, platinum-containing therapy received gemcitabine 1000 mg/m(2) on days 1 and 8 and carboplatin AUC 4 on day 1 (after gemcitabine) every 21 days for up to six cycles. RESULTS: Of the 40 enrolled/evaluable patients, 6 (15%) had complete response and 19 (47.5%) had partial response (PR), including one patient with PR in nonmeasurable disease (PRNM), for an overall response rate of 62.5% (95% CI, 45.8-77.3%). The median duration of response was 7.8 months (95% CI, 6.7-10.0), the median time to progressive disease was 9.6 months (95% CI, 8.5-11.0), and the median time to treatment failure was 9.3 months (95% CI, 8.2-10.4). The main grade 3/4 toxicities were neutropenia (78% of patients), leukopenia (30%), thrombocytopenia (18%), and anemia (15%); no grade 4 nonhematologic toxicities occurred, and grade 3 nonhematologic toxicities were mild. CONCLUSIONS: The combination of gemcitabine and carboplatin is active and feasible in platinum-sensitive patients with recurrent ovarian cancer. This regimen is undergoing further evaluation in a large phase III trial.