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PURPOSE: Guideline consistency in the prevention of chemotherapy-induced nausea and vomiting (CINV) remains low (29% in the Pan European Emesis Registry study) and very low (11%) in regimens with a high emetogenic risk. The aim of this study was to evaluate the guideline consistency of CINV prophylaxis for acute emesis in daily clinical practice in Italy. METHODS: This was a prospective, observational, multicenter study. Patients scheduled to receive antitumor treatment on a single prespecified day were included. Data on patient characteristics (demographic and clinical), type of anticancer therapy, and type of antiemetic therapy prescribed for acute emesis were collected on electronic data capture forms. Chemotherapy regimens and antiemetic prophylaxis were categorized according to the MASCC 2011 guidelines. The study was approved by the local ethics committees. RESULTS: From July 2013 to February 2014, a total of 502 patients were enrolled at 26 study sites. Median age was 62 years (range 27-87 years). Colorectal cancer and breast cancer were the most common malignancies. The emetogenic potential of the chemotherapy regimens used was high (HEC) (23.7%), moderate (MEC) (40.6%), low (31.3%) or minimal (4.4%). Overall, guideline consistency was 19.3%. Consistency reached 45% when the various 5HT3 receptor antagonists were considered equivalent and interchangeable in MEC regimens. Adherence to guidelines was lowest for MEC and Minimal risk groups. Ten percent of patients in HEC and MEC regimens did not receive any 5HT3 receptor antagonists. NK1 receptor antagonists were used in 8% of all regimens. CONCLUSIONS: Our study indicates that antiemetic guideline inconsistency remains an issue in daily clinical oncology practice in Italy.
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Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Náusea/inducido químicamente , Náusea/prevención & control , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéutico , Vómitos/inducido químicamente , Vómitos/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Instituciones Oncológicas , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Antagonistas del Receptor de Neuroquinina-1/uso terapéutico , Guías de Práctica Clínica como Asunto , Estudios ProspectivosRESUMEN
BACKGROUND: Tumour stage and the appropriate course of treatment in patients with breast cancer are primarily characterized by the state of metastasis in the axillary lymph nodes. In recent years, substantial research has focused on the prediction of lymph node status based on various pathological and molecular markers in order to obviate the necessity to carry out axillary dissection. In the present study, artificial neural network (ANN) is employed as the analysis platform to examine the prognostic significance of a group of well-established prognostic markers for breast cancer outcome prediction in terms of nodal status. Furthermore, we investigated existing interactions between these markers. PATIENTS AND METHODS: The data set contained 66 patient records, where 5 pathological and molecular markers including tumour size, oestrogen receptor status (ER), progesterone receptor status (PR), Ki-67 and p53 expression had been assessed for each patient. The spread of metastasis to the axillary lymph nodes was clinically diagnosed and patients were accordingly categorized into node-positive and node-negative groups. The aforementioned markers were analyzed using a probabilistic neural network (PNN) for nodal status prediction which was considered as the network output. Furthermore, the interactions between these markers were evaluated using different marker combinations as the network input for finding the best marker arrangement for nodal predication. RESULTS: The best prediction accuracy was obtained by a 3-marker combination including tumour size, PR and p53 with 71% accuracy for nodal prediction. Leaving out ER and PR from the full marker set showed approximately the same variations in the results, which is an indication of the direct correlation of these two markers. Furthermore, tumour size was proved to be the most significant individual marker for predicting nodal metastasis. However, when used in combination with Ki-67 the prediction results drop significantly. CONCLUSION: The results presented here indicate that molecular and pathological markers can provide useful information for early-stage prognosis. However, the interactions between these markers must be considered in order to achieve accurate and reliable prediction.
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Neoplasias de la Mama/patología , Antígeno Ki-67/metabolismo , Metástasis Linfática , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Femenino , Humanos , PronósticoRESUMEN
Adjuvant therapy represents the gold standard treatment for radically resected pancreatic cancer. Results from randomized clinical trials confirmed the efficacy of adjuvant therapy for pancreatic cancer but did not define what is the "right choice" in terms of type of antiblastic drug (among gemcitabine, 5-fluorouracil or other drugs), role of polychemotherapy and chemoradiotherapy. The objective of our study was to evaluate the efficacy and toxicity of adjuvant chemotherapy and chemoradiotherapy for radically resected pancreatic cancer through a systematic review of literature data, emphasizing the benefits regarding overall survival, disease-free survival and toxicity.
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Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Quimioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante/métodos , Ensayos Clínicos Fase II como Asunto/estadística & datos numéricos , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Terapia Combinada , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Humanos , Mitomicina/administración & dosificación , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/terapia , Guías de Práctica Clínica como Asunto , Radioterapia Adyuvante/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Análisis de Supervivencia , GemcitabinaRESUMEN
INTRODUCTION: Uterine leiomyosarcoma is one of the most frequent uterine sarcomas. In the metastatic setting it is sensitive to doxorubicin, ifosfamide, gemcitabine, docetaxel and a few other drugs, but time to progression is generally short. For this reason prognosis is often poor and there are few reports in the literature of long responders. CASE PRESENTATION: We report a case of a 40-year-old Caucasian woman with metastatic uterine leiomyosarcoma who began treatment six years before the presentation of this case report and for the following six years underwent ten lines of chemotherapy, achieving excellent results and a good quality of life. Among the treatments administered we observed a long response to temolozomide, an unconventional drug for this kind of disease. CONCLUSION: Although there are few chemotherapeutic options for the management of metastatic uterine leiomyosarcoma, a small number of patients have an unexpected long lasting response to treatment. For this reason further research is needed to identify new therapeutic agents and the predictive factors for the achievement of response.
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INTRODUCTION: The TORCH (Tarceva or Chemotherapy) trial randomized patients with advanced non-small-cell lung cancer to first-line erlotinib followed by second-line cisplatin/gemcitabine versus. standard inverse sequence. The trial, designed to test noninferiority in overall survival, was stopped at interim analysis because of inferior survival in the experimental arm. Quality of life (QoL), a secondary outcome, is reported here. METHODS: QoL was assessed at baseline and every 3 weeks during first-line, using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 and QLQ-lung cancer specific module (LC13). Mean changes from baseline within arms were reported. QoL response and time-to-deterioration of QoL using a competing-risk approach were compared between treatment arms. RESULTS: Six hundred and thirty patients (83%) completed baseline questionnaires. Compliance was affected by differential treatment efficacy, but was similar between arms for patients without progression or death. Significant differences in QoL responses were observed favoring chemotherapy for pain, sleeping, dyspnea, diarrhea, and favoring erlotinib for vomiting, constipation, sore mouth, and alopecia. In the small subset of patients with EGFR-mutated tumors, all selected items (global QoL, physical functioning, cough, dyspnea and pain) improved, whereas worsening or no change was observed in wild-type patients. Improvement was particularly evident in the first-line erlotinib arm as for global QoL and physical functioning. CONCLUSIONS: QoL was impacted by differential toxicity and efficacy between arms. Functional domains and global QoL did not differ, although some symptoms were better controlled with chemotherapy in unselected non-small-cell lung cancer patients.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Calidad de Vida , Adenocarcinoma/patología , Anciano , Carcinoma de Células Grandes/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Clorhidrato de Erlotinib , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Quinazolinas/administración & dosificación , Proyectos de Investigación , Terapia Recuperativa , Encuestas y Cuestionarios , GemcitabinaRESUMEN
PURPOSE: This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II to IIIA operable breast cancer. The primary aim was to estimate the percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes). PATIENTS AND METHODS: In the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/m(2)) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every 3 weeks. The patients randomly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly; in arm B patients received lapatinib 1,500 mg orally (PO) daily; and in arm C, patients received trastuzumab and lapatinib 1,000 mg PO daily. RESULTS: A total of 121 patients were randomly assigned. Diarrhea and dermatologic and hepatic toxicities were observed more frequently in patients receiving lapatinib. No episodes of congestive heart failure were observed. The rates of breast-conserving surgery were 66.7%, 57.9%, and 68.9% in arms A, B and C, respectively. The pCR rates were 25% (90% CI, 13.1% to 36.9%) in arm A, 26.3% (90% CI, 14.5% to 38.1%) in arm B, and 46.7% (90% CI, 34.4% to 58.9%) in arm C (exploratory P = .019). CONCLUSION: The primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib. These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Ciclofosfamida/administración & dosificación , Esquema de Medicación , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Lapatinib , Persona de Mediana Edad , Terapia Neoadyuvante , Paclitaxel/administración & dosificación , Quinazolinas/administración & dosificación , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismoRESUMEN
This multicenter phase II trial was designed to evaluate the activity of lapatinib in metastatic breast cancer patients with HER2-negative primary tumors and HER2-positive circulating tumor cells (CTCs). In this study MBC patients with HER2-negative primary tumors and HER2-positive CTCs previously treated with at least a first-line therapy for metastatic disease received lapatinib 1500 mg/day. The CellSearch System® was used for CTCs isolation and bio-characterization. HER2 status was assessed on CTCs by immunofluorescence. A case was defined as CTCs positive if ≥2 CTC/7.5 ml of blood were isolated and HER2-positive if ≥50% of CTCs were HER2-positive. 139 HER2-negative patients were screened, 96 patients were positive for CTCs (mean number of CTCs: 85; median number of CTCs: 19; range 2-1637). Seven of the 96 patients (7%) had ≥50% HER2-positive CTCs and were eligible for treatment with lapatinib. No objective tumor responses occurred in this population. In one patient, disease stabilization lasting 254 days (8.5 months) was observed. From the findings of this study, we concluded that a subset of patients with a HER2-negative primary tumor presents HER2-positive CTCs during disease progression, although the HER2 shift rate seems to be lower than previously reported. Despite the lack of objective response, the durable disease stabilization observed in one patient cannot rule out the hypothesis that lapatinib may have some activity in this patient population. However, considering that only 1/139 screened patients may potentially have derived benefit from this approach, future trials designed according to the presented strategy cannot be recommended.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Lobular/tratamiento farmacológico , Células Neoplásicas Circulantes/metabolismo , Quinazolinas/uso terapéutico , Receptor ErbB-2/metabolismo , Antineoplásicos/farmacología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/metabolismo , Carcinoma Lobular/secundario , Femenino , Humanos , Lapatinib , Persona de Mediana Edad , Quinazolinas/farmacología , Resultado del TratamientoRESUMEN
PURPOSE: Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy. PATIENTS AND METHODS: Chemotherapy-naive patients with stage IC to IV ovarian cancer (age ≤ 75 years; Eastern Cooperative Oncology Group performance status ≤ 2) were randomly assigned to carboplatin area under the curve (AUC) 5 plus paclitaxel 175 mg/m(2) or to carboplatin AUC 5 plus PLD 30 mg/m(2), every 3 weeks for six cycles. Primary end point was progression-free survival (PFS). With 632 events in 820 enrolled patients, the study would have 80% power to detect a 0.80 hazard ratio (HR) of PFS. RESULTS: Eight hundred twenty patients were randomly assigned. Disease stages III and IV were prevalent. Occurrence of PFS events substantially slowed before obtaining the planned number. Therefore, in concert with the Independent Data Monitoring Committee, final analysis was performed with 556 events, after a median follow-up of 40 months. Median PFS times were 19.0 and 16.8 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.95; 95% CI, 0.81 to 1.13; P = .58). Median overall survival times were 61.6 and 53.2 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.89; 95% CI, 0.72 to 1.12; P = .32). Carboplatin/PLD produced a similar response rate but different toxicity (less neurotoxicity and alopecia but more hematologic adverse effects). There was no relevant difference in global quality of life after three and six cycles. CONCLUSION: Carboplatin/PLD was not superior to carboplatin/paclitaxel, which remains the standard first-line chemotherapy for advanced ovarian cancer. However, given the observed CIs and the different toxicity, carboplatin/PLD could be considered an alternative to standard therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/toxicidad , Carboplatino/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Polietilenglicoles/administración & dosificación , Calidad de VidaRESUMEN
Capecitabine is now-a-days rapidly replacing 5-Fluorouracil in daily clinical practice. Neurologic toxicity during a treatment with fluoropyrimidines, as 5-fluorouracil, represents a well-known side-effect, largely described in literature. Central nervous system (CNS) toxicity, mainly encephalopathy with or without seizures, occurs occasionally even when conventional doses are used. CNS toxicity incidence increases markedly when the blood-brain barrier is either overwhelmed or bypassed (Hildebrand J. Neurological complications of cancer chemotherapy. Curr Opin Oncol 2006; 18: 321-324). Peripheral nervous system (PNS) toxicity is more common because proximal and distal extremities of the peripheral nerves are not protected by a blood-brain like barrier and peripheral neuropathy remains a major limiting factor for the administration of conventional doses of several agents (Saif W, Wood TE, McGee PJ and Diasio RB. Peripheral neuropathy associated with capecitabine, Anticancer Drugs 2004;15: 767-771). Capecitabine is a prodrug of 5-fluorouracil, more easily administered by mouth; its transformation in 5-fluorouracil is performed in the liver. There are only a few reports on the toxic neurological side-effects of capecitabine. We describe in our report a rare case of toxic encephalopathy in a 82-year-old female, with a brief review of literature. In the literature reviewed, we found 12 neurologic episodes due to capecitabine lasting between a few days till some months. All clinical symptoms of the cases described in literature, obtained a complete regression with the discontinuation of capecitabine. A relation was not found with dihydropyrimidine dehydrogenase (DPD) mutation, also if pharmacologic and pharmacogenetic assessment should be done for this drug, especially in old patients. Toxic encephalopathy represents a rare event during capecitabine treatment and on the bases of the data found, is fairly managed in the clinical setting. The knowledge of the natural history of the toxic effect allows the use of the drug also in old patients.
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Adenocarcinoma/tratamiento farmacológico , Antimetabolitos Antineoplásicos/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Síndromes de Neurotoxicidad/etiología , Adenocarcinoma/secundario , Factores de Edad , Anciano de 80 o más Años , Neoplasias Óseas/secundario , Capecitabina , Neoplasias Colorrectales/patología , Desoxicitidina/efectos adversos , Resultado Fatal , Femenino , Fluorouracilo/efectos adversos , Humanos , Síndromes de Neurotoxicidad/diagnóstico , Selección de Paciente , Medición de Riesgo , Factores de RiesgoRESUMEN
The introduction of cisplatin in cancer treatment represents an important achievement in the oncologic field. Many types of cancers are now treated with this drug, and in testicular cancer patients major results are reached. Since 1965, other compounds were disovered and among them carboplatin and oxaliplatin are the main Cisplatin analogues showing similar clinical efficacy with a safer toxicity profile. Lipoplatin is a new liposomal cisplatin formulation which seems to have these characteristics. Lipoplatin was shown to be effective in NSCLC both in phase 2 and phase 3 trials, with the same response rate of Cisplatin, a comparable overall survival but less toxicity. A new protocol aiming to elucidate the double capacity of Lipoplatin to act as a chemotherapeutic and angiogenetic agent in triple-negative breast cancer patients is upcoming.
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INTRODUCTION: Small cell neuroendocrine cancer of the breast is a rare tumor with less than 30 cases reported in the literature. The morphological and immunohistochemical patterns of this tumor are similar to small cell neuroendocrine cancer of the lung. For this reason, it is often difficult to distinguish a primary small cell neuroendocrine cancer of the breast from a metastatic lesion from other sites. CASE PRESENTATION: We report and characterize with immunohistochemical techniques a case of primary small cell neuroendocrine cancer of the breast occurring in a 40-year-old Caucasian woman. A palpable and mobile 3.0 cm tumor was located in the upper-outer quadrant of her right breast. Lumpectomy and subsequent radical mastectomy with axillary lymph node resection were performed. Microscopically, the tumor consisted predominantly of a diffuse proliferation of small oat cells. The tumor cells were positive for neuroendocrine markers chromogranin A and synaptophysin. One of 16 lymph nodes was metastatic. A correct treatment needs to be chosen. CONCLUSIONS: It has recently been demonstrated that early small cell neuroendocrine cancer of the breast shows a good prognosis with adjuvant treatments with high disease free survival. Our patient is alive and well without disease eight years after treatment. We performed an adjuvant therapy with the classic scheme doxorubicin and cyclophosphamide, followed by carboplatin and etoposide. A more extensive review is required to define a standard treatment protocol for this rare neoplasm.
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BACKGROUND: Aim of our work was to assess the role of prognostic and predictive factors in patients to be treated with II and III line chemotherapy in metastatic colorectal cancer. METHODS: All the patients with metastatic colorectal cancer treated with at least one line of chemotherapy for metastatic disease and progressed after I line chemotherapy were considered eligible and enrolled into the trial. RESULTS: Twenty-six out of 51 consecutive, and potentially eligible patients (51%) were considered eligible and included into the analysis. The median time to progression to I line chemotherapy was 6.7 months with no significant differences between FOLFOX and FOLFIRI (respectively 10 and 6.7 months, p = 0.71). The I line response rate was 57.7% with no significant differences between FOLFOX and FOLFIRI (respectively 46.1% vs 70%, p = 0.4). A significant improve in overall survival was observed for I line responder patients (respectively, 60 and 12 months for responder and non-responder patients, p = 0.0037), with a significant correlation with the time to progression to I line chemotherapy (p = 0.041). No statistical difference was observed for the number of lines of treatment (3 vs 2, p = 0.3), the treatment sequence (FOLFOX-->FOLFIRI vs FOLFIRI-->FOLFOX, p = 0.94), patient's age (p = 0.105), patient sex (p = 0.055), II line response rate (p = 0.987) and time to progression to II line chemotherapy (p = 0.151) in multivariate analysis. CONCLUSIONS: Our data seem to suggest a prognostic significance of I line response rate and time to progression in patients with metastatic colorectal cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/diagnóstico , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The relationship between nail and bone may be measurable, thus making the fingernail a potentially valuable tool for assessing bone health for women receiving treatment for breast cancer. In the BIG 1-98 Fingernail Pilot Substudy, Bone Quality Test (BQT) scores of fingernails were measured at two assessment timepoints. METHODS: Thirteen eligible patients were enrolled into the substudy during their treatment with tamoxifen (four patients) or letrozole (nine patients). Two fingernails were tested and BQT scores averaged for two assessments six months apart. RESULTS: BQT scores collected six months later (second assessment) significantly decreased compared with those at first collection (p=0.007) regardless of treatment and prior fracture. CONCLUSION: The reduction of BQT scores observed in the patients of our small exploratory study during exposure to bone-altering breast cancer treatments is an incentive for larger studies using this technique.
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Antineoplásicos Hormonales/farmacología , Densidad Ósea/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Nitrilos/farmacología , Tamoxifeno/farmacología , Triazoles/farmacología , Anciano , Antineoplásicos Hormonales/uso terapéutico , Femenino , Humanos , Letrozol , Persona de Mediana Edad , Uñas , Nitrilos/uso terapéutico , Posmenopausia , Tamoxifeno/uso terapéutico , Resultado del Tratamiento , Triazoles/uso terapéuticoRESUMEN
Numerous studies referring to conventional chemotherapy for aggressive fibromatosis with the use of doxorubicin, cyclophosphamide, vincristin, vinblastine and other drugs have been published. Imatinib mesylate is a recently developed oral anticancer agent designed to selectively inhibit tyrosine kinases implicated in oncogenesis and it seems to represent a promising opportunity (also in first line) in the treatment of patients with advanced disease not candidate to prior surgery.
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Antineoplásicos/uso terapéutico , Fibromatosis Agresiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzamidas , Quimioterapia Adyuvante , Fibromatosis Agresiva/patología , Fibromatosis Agresiva/cirugía , Humanos , Mesilato de Imatinib , Masculino , Metotrexato/administración & dosificación , Piperazinas/administración & dosificación , Pirimidinas/administración & dosificación , Resultado del Tratamiento , Vinblastina/administración & dosificaciónRESUMEN
The incidence of second non-breast primary cancer following adjuvant treatment was evaluated using data from patients enrolled from 1978 to 1999 in four International Breast Cancer Study Group (IBCSG) trials. The occurrence of these tumours as sites of the first failure was assessed separately for two treatment comparisons: toremifene versus tamoxifen for 5 years in 1035 patients in IBCSG Trials 12-93 and 14-93 with a median follow-up of 8 years and endocrine therapy (toremifene or tamoxifen) versus chemo-endocrine therapy (CMF or AC plus toremifene or tamoxifen) in 1731 patients from IBCSG Trials III, VII and 12-93, with a combined median follow-up of 14 years. No significant differences in second non-breast primary tumours were observed in either comparison. In particular, the incidences of second primary uterine tumours with toremifene and tamoxifen were similar and no significant increase of secondary leukaemias was observed with chemo-endocrine therapy compared with endocrine therapy.
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Antineoplásicos Hormonales/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Primarias Secundarias/inducido químicamente , Adulto , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante/efectos adversos , Estudios de Cohortes , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Mastectomía , Persona de Mediana Edad , Análisis de Supervivencia , Tamoxifeno/administración & dosificación , Tamoxifeno/efectos adversos , Tamoxifeno/uso terapéutico , Toremifeno/administración & dosificación , Toremifeno/efectos adversos , Toremifeno/uso terapéuticoRESUMEN
BACKGROUND: A variety of molecular markers have been evaluated for the development of a non-invasive approach to the diagnosis of colorectal cancer. We aimed to validate the diagnostic accuracy, using the same threshold as in the previous pilot study, of fluorescent long DNA test as a relatively simple and inexpensive tool for colorectal cancer detection. METHODS: A case-control study was conducted on 100 healthy subjects and 100 patients at first diagnosis of colorectal cancer. Human long-fragment DNA in stool was quantified by fluorescence primers and a standard curve and expressed in DNA nanograms. RESULTS: We validated the 25-ng value, which emerged as the most accurate cut-off in the pilot study, obtaining 79% (95% CI, 71-87%) sensitivity and 89% (95% CI, 83-95%) specificity. Specificity was very high for all cut-off values (15-40 ng) analyzed, ranging from 78 to 96%. Sensitivity was only slightly lower, reaching 84% at the lowest cut-off and maintaining a good level at the higher values. Diagnostic potential was independent of gender, age and tumor site. CONCLUSION: Fecal DNA analysis is a non-invasive and fairly simple test showing high diagnostic potential. These characteristics, together with the small amount of stool required, make it potentially suitable to be used alongside or as an alternative to current non-invasive screening approaches. Our next step will be to validate these results in a large-scale cohort study of a screening population, which is needed prior to implementation into clinical practice.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , ADN/genética , Detección Precoz del Cáncer , Heces/química , Proteína de la Poliposis Adenomatosa del Colon/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Cartilla de ADN/genética , Femenino , Colorantes Fluorescentes/química , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Lipoplatin is a novel liposomal cisplatin formulation with reduced adverse side effects compared with its parental compound, cisplatin. The aims of this preclinical study were to compare lipoplatin and cisplatin cytotoxicity in vitro in established cell lines derived from non-small cell lung cancer, renal cell carcinoma, and in normal hematopoietic cell precursors, and to identify biological markers associated with sensitivity and resistance. Our results showed a superior cytotoxicity in all tumor cell models and a much lower toxicity in normal cells for lipoplatin compared with cisplatin, suggesting a higher therapeutic index for the liposomal compound. Moreover, RT-PCR analysis of molecular markers known to be related to cisplatin resistance showed a direct correlation between cisplatin and lipoplatin resistance and ERCC1 and LRP expression. In conclusion, lipoplatin showed a higher antitumor activity in both tumor histotypes investigated and was found to be safer than the parent compound, cisplatin. Moreover, ERCC1 and LRP expression levels would seem to be valid predictors of sensitivity or resistance to these drugs.
Asunto(s)
Antineoplásicos/farmacología , Cisplatino/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Daño del ADN , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Humanos , Concentración 50 InhibidoraRESUMEN
Nowadays, neoadjuvant radiotherapy represents the gold standard in the treatment of locally-advanced rectal cancer. Likewise, a lot of evidences seems to suggest that preoperative chemotherapy could improve the local control of the disease, favour the downstaging of the tumor, and make possible an higher number of conservative, sphincter-sparing surgical approaches. In our paper we systematically reviewed the evidences of literature to detect both the main benefits and the limits of pre-operative chemotherapy in the treatment of locally advanced rectal cancer. Moreover, we critically reviewed both the main outcomes of preoperative chemotherapy (overall survival, disease-free interval, number of conservative, sphincter-sparing surgical approaches) and its safety (acute and chronic safety), to give clinicians an evidence-based support for their clinical practice.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Ensayos Clínicos Controlados como Asunto , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Metaanálisis como Asunto , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/prevención & control , Guías de Práctica Clínica como Asunto , Cuidados Preoperatorios , Radioterapia/efectos adversos , Neoplasias del Recto/mortalidad , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Factores de Tiempo , Resultado del TratamientoRESUMEN
The randomized multicenter study on rapidly proliferating breast cancer, assessed according to thymidine labelling index (TLI), was activated at the end of the 1980s. The present work investigated whether and to what degree the short-term advantages observed from adjuvant CMF (cyclophosphamide, methotrexate, 5-fluorouracil) were maintained at a longer follow-up. Two hundred and eighty-one patients with node-negative and high TLI tumors were randomized to receive six cycles of CMF or no further treatment. At a median follow-up of 12 years, CMF produced a 25% and 20% relative reduction in relapse and death cumulative incidence, respectively. A breakdown analysis identified a subgroup of patients with intermediate proliferating tumors for whom a 70% and 73% reduction in relapse and death was observed in the intention-to-treat population. An even higher reduction of 80% and 84% in relapse and death was seen for the patients who had received the full CMF dose. We identified a subgroup of patients with intermediate proliferating tumors in whom the high benefit obtained from adjuvant CMF was maintained at a long-term follow up.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Proliferación Celular/efectos de los fármacos , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Italia , Estimación de Kaplan-Meier , Ganglios Linfáticos/patología , Metotrexato/administración & dosificación , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
UNLABELLED: GOAL OF THE WORK: Anemia is a common side effect of chemotherapy. Limited information exists about its incidence and risk factors. The objective of this study was to evaluate the incidence of anemia and risk factors for anemia occurrence in patients with early breast cancer who received adjuvant chemotherapy. MATERIALS AND METHODS: We evaluated risk factors for anemia in pre- and post/perimenopausal patients with lymph node-positive early breast cancer treated with adjuvant chemotherapy in two randomized trials. All patients received four cycles of doxorubicin and cyclophosphamide (AC) followed by three cycles of cyclophosphamide, methotrexate, fluorouracil (CMF). Anemia incidence was related to baseline risk factors. Multivariable analysis used logistic and Cox regression. MAIN RESULTS: Among the 2,215 available patients, anemia was recorded in 11% during adjuvant chemotherapy. Grade 2 and 3 anemia occurred in 4 and 1% of patients, respectively. Pretreatment hemoglobin and white blood cells (WBC) were significant predictors of anemia. Adjusted odds ratios (logistic regression) comparing highest versus lowest quartiles were 0.18 (P < 0.0001) for hemoglobin and 0.52 (P = 0.0045) for WBC. Age, surgery type, platelets, body mass index, and length of time from surgery to chemotherapy were not significant predictors. Cox regression results looking at time to anemia were similar. CONCLUSIONS: Moderate or severe anemia is rare among patients treated with AC followed by CMF. Low baseline hemoglobin and WBC are associated with a higher risk of anemia.