RESUMO
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) still represents a common side-effect of chemotherapy, and often, its perception differs between patients and healthcare professionals. The aim of this study was to evaluate the agreement on the perception of CINV and other items among clinicians, patients, and nurses. METHODS: This observational prospective study was part of an evaluation program promoted by the Women Against Lung Cancer in Europe (WALCE) Onlus. From August 2015 to February 2016, a survey was administered in 11 oncologic institutions to 188 stage IV lung cancer patients and to their oncologists and nurses during first-line chemotherapy. Our survey investigated 11 aspects: anxiety, mood, weakness, appetite, nausea, vomiting, pain, drowsiness, breath, general condition, and trust in treatments. These items were assessed through Numerical Rating Scale at four consecutive evaluations: at T0 (immediately prior to the first cycle), at T1 (immediately prior to the second cycle), at T2 (immediately prior to the third cycle), and at T3 (immediately prior to the fourth cycle). Clinician versus patient (CvP), nurse versus patient (NvP), and clinician versus nurse (CvN) agreements were estimated applying Weighted Cohen's kappa. A multivariate logistic model and generalized equation estimates were applied to evaluate factors possibly influencing CINV development. RESULTS: The incidence of patients reporting CINV varied from 40% at T0 to 71% at T3. Both CvP and NvP agreement on the investigated items were mainly moderate, slightly increasing over time, and becoming substantial for some items, in particular for NvP. Pre-chemotherapy anxiety in its mild, moderate, and severe manifestations, as well as mild, moderate, and severe anxiety experienced after chemotherapy start, exposed patients to a higher risk of anticipatory and acute/delayed CINV, respectively. CONCLUSIONS: Despite clinical staff awareness of patients' status and perceptions, CINV still represents a clinical problem. This study confirms that particular attention should be paid to anxiety due to its key role in CINV development.
Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Neoplasias Pulmonares/complicações , Náusea/induzido quimicamente , Vômito/induzido quimicamente , Adulto , Idoso , Antieméticos/farmacologia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The prognostic and predictive role of KRAS mutations in advanced nonsmall-cell lung cancer (NSCLC) is still unclear. TAILOR prospectively assessed the prognostic and predictive value of KRAS mutations in NSCLC patients treated with erlotinib or docetaxel in second line. PATIENTS AND METHODS: NSCLC patients from 52 Italian hospitals were genotyped for KRAS and EGFR mutational status in two independent laboratories. Wild-type EGFR patients (N = 218) received first-line platinum-based chemotherapy and were randomly allocated at progression to erlotinib or docetaxel. Overall survival (OS) according to KRAS mutational status was the primary end point. RESULTS: KRAS mutations were present in 23% of TAILOR randomized cases. The presence of a KRAS mutation did not adversely affect progression-free (PFS) or overall (OS) survival [hazard ratio (HR) PFS = 1.01, 95% confidence interval (CI) 0.71-1.41, P = 0.977; OS = 1.24, 95% CI 0.87-1.77, P = 0.233], nor influenced treatment outcome (test for interaction: OS P = 0.965; PFS P = 0.417). Patients randomized to docetaxel treatment experienced longer survival independently from the KRAS mutational status of their tumors (HR: mutated KRAS 0.81, 95% CI 0.45-1.47; wild-type KRAS 0.79, 95% CI 0.57-1.10). CONCLUSION: In TAILOR, KRAS was neither prognostic nor predictive of benefit for either docetaxel or erlotinib. Docetaxel remains superior independently from KRAS status for second-line treatment in EGFR wild-type advanced NSCLC patients. CLINICAL TRIAL REGISTRATION: NCT00637910.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Docetaxel , Cloridrato de Erlotinib/administração & dosagem , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Taxoides/administração & dosagemRESUMO
PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangement confers sensitivity to ALK inhibitors (ALKis) in non-small-cell lung cancer (NSCLC). Although several drugs provided an impressive outcome benefit, the most effective sequential strategy is still unknown. We describe outcomes of real-life patients according to the treatment strategy received. PATIENTS: We retrospectively collected 290 ALK rearranged advanced NSCLC diagnosed between 2011 and 2017 in 23 Italian institutions. RESULTS: After a median follow-up of 26 months, PFS for crizotinib and a new generation ALKis were 9.4 [CI 95% 7.9-11.2] and 11.1 months [CI 95% 9.2-13.8], respectively, while TTF were 10.2 [CI 95% 8.5-12.6] and 11.9 months [CI 95% 9.7-17.4], respectively, being consistent across the different settings. The composed outcomes (the sum of PFS or TTF) in patients treated with crizotinib followed by a new generation ALKis were 27.8 months [CI 95% 24.3-33.7] in PFS and 30.4 months [CI 95% 24.7-34.9] in TTF. The median OS from the diagnosis of advanced disease was 39 months [CI 95% 31.8-54.5]. Patients receiving crizotinib followed by a new generation ALKis showed a higher median OS [57 months (CI 95% 42.0-73.8)] compared to those that did not receive crizotinib [38 months (CI 95% 18.6-NR)] and those who performed only crizotinib as target agent [15 months (CI 95% 11.3-34.0)] (P < 0.0001). CONCLUSION: The sequential administration of crizotinib and a new generation ALKis provided a remarkable clinical benefit in this real-life population, being an interesting option to consider in selected patients.
Assuntos
Quinase do Linfoma Anaplásico/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe/uso terapêutico , Feminino , Rearranjo Gênico , Humanos , Itália , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemAssuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Genes ras , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/patologiaRESUMO
BACKGROUND: In order to combine an active regimen with a simultaneous efficient mobilization of peripheral blood precursor cells (PBPC), we explored the combination of Docetaxel 75 mg/m2 and Epirubicin 120 mg/m2 with G-CSF 5 mcg/Kg/day s.c. to mobilize PBPC in breast cancer patients to support high-dose chemotherapy (HDC). PATIENTS AND METHODS: Forty patients were enrolled: 27 high risk and 13 metastatic. The entire procedure, including chemotherapy and PBPC collection, was on an outpatient basis. RESULTS: The median day of starting apheresis was day +10 (range 10-12) and the average value of circulating CD34+ cells at peak was 175/microliter (range 33-403). The median yield of CD34+ cells per apheresis was 8.76 x 10(6)/Kg (range 1.83-27.87). None of the patients developed side effects which required hospitalization. All patients enrolled successively received HDC as consolidation treatment. High risk patients received one and metastatic patients two HDC with PBPC reinfusion. All patients obtained a complete engraftment. No significant differences between high-risk and metastatic patients were observed. CONCLUSIONS: Our study suggests that the combination of Docetaxel, Epirubicin, and G-CSF is feasible, safe and efficient outpatient mobilizing treatment for patients with breast cancer receiving HDC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Epirubicina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Paclitaxel/análogos & derivados , Paclitaxel/uso terapêutico , Taxoides , Adulto , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/sangue , Docetaxel , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Células-Tronco Hematopoéticas/citologia , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Resultado do TratamentoRESUMO
A 53-year-old woman experienced rapidly progressing liver failure four years after a quadrantectomy for a breast carcinoma. She had received adjuvant chemotherapy and radiotherapy, and second-line chemotherapy for bone metastasis one year earlier. The hepatic failure manifested with ascites, jaundice, elevation of serum bilirubin and hepatic enzyme levels and hypoalbuminemia. Imaging studies showed an enlarged liver without metastatic lesions. The patient died of hepatic decompensation within two weeks. Liver examination at autopsy revealed massive neoplastic infiltration consistent with a primary breast carcinoma. It is important to realize that this unusual pattern of liver metastasis cannot be demonstrated even with the most advanced techniques of instrumental diagnosis (CT scan, ultrasonography and magnetic resonance imaging), and should be taken into account in the differential diagnosis of rapidly progressing liver failure.
Assuntos
Neoplasias da Mama/patologia , Carcinoma/secundário , Falência Hepática/etiologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Autopsia , Neoplasias Ósseas/secundário , Carcinoma/metabolismo , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Falência Hepática/tratamento farmacológico , Falência Hepática/metabolismo , Testes de Função Hepática , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Pessoa de Meia-Idade , Falha de TratamentoRESUMO
In 1989 we started an accelerated hyperfractionated schedule of radiotherapy (two 1.6 Gy daily fractions) in standard risk localized Ewing's sarcoma of bone, with the aim at reducing late effects in young patients and at improving disease control through a better integration of treatment modalities. From 1991, the same schedule was used in preoperative radiotherapy of adult soft tissue sarcomas of the extremities: the main purpose was to reduce the time to surgery and to evaluate surgical complications in comparison with a previous experience of hypofractionated radiotherapy (one 3 Gy daily fraction). From 1991 to 1997, 76 patients with Ewing's sarcoma and 24 patients with soft tissue sarcoma were treated at our Institution. Results and complication rates are analyzed in comparison with historical data. In Ewing's sarcoma, a correct evaluation of improvement in local control was difficult because of changing treatment policy (bulky disease was not included in the present series). Late effects, as evaluated in patients with a minimum follow-up of 3 years, occurred with similar incidence, but at higher total dose levels in patients treated with accelerated hyperfractionation. In patients with soft tissue sarcomas, incidence of surgical complications is reduced as compared to historical experience. Major problems of wound healing were seen in association with intraoperative brachitherapy boost.
Assuntos
Braço , Neoplasias Ósseas/radioterapia , Fracionamento da Dose de Radiação , Perna (Membro) , Neoplasias de Tecido Muscular/radioterapia , Sarcoma/radioterapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Muscular/tratamento farmacológico , Neoplasias de Tecido Muscular/cirurgia , Radioterapia Adjuvante , Indução de Remissão , Sarcoma de Ewing/radioterapia , Resultado do TratamentoRESUMO
BACKGROUND: Increased knowledge about the treatment of pancreatic cancer has influenced the management of locally advanced and metastatic disease. Nonetheless, prognosis remains dismal (24%, 1-year survival). The impact on overall survival (OS) of second-line therapy has not been clarified and the use of platinum salts and/or fluoropyrimidines is hotly debated. It is the hope that future treatment can be tailored to predict chemosensitivity in order to improve outcomes in patients with locally advanced and metastatic pancreatic cancer. Since DNA-damaging agents could be one therapeutic option, a retrospective multicenter study was performed to evaluate the efficacy of salvage treatment with the hypothesis that levels of the DNA repair gene excision repair cross complementing 1 (ERCC1) could influence OS. PATIENTS AND METHODS: In a population of 160 patients treated with fluoropyrimidine-based second-line chemotherapy, expression levels of ERCC1 were determined by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). In 108 patients with locally advanced and metastatic pancreatic cancer treated with either fluoropyrimidines and platinum salts (group A=58) or fluoropyrimidines alone (group B=50), ERCC1 levels were correlated with OS, time to progression and response to chemotherapy. RESULTS: Median survival was significantly higher in group A with low ERCC1 levels [11.9 versus 9.9 months; p ≤ 0.05] (median follow-up 24 months). Moreover in the same group, a trend towards longer time to progression was observed. No differences in OS were observed when ERCC1 was studied (low versus high) in patients not treated with platinum salts. On multivariate analysis of pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for OS. CONCLUSION: The results of this study indicate that ERCC1 may predict survival in pancreatic cancer patients treated by platinum and fluoropyrimidine as second-line chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Pirimidinas/uso terapêutico , Adulto , Idoso , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Endonucleases/biossíntese , Endonucleases/genética , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/genética , Pirimidinas/administração & dosagem , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Terapia de Salvação , Taxa de SobrevidaRESUMO
BACKGROUND: Platinum-based combination chemotherapy is currently recommended as the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its benefit seems limited to fit patients with a performance status (PS) of 0 or 1. For PS2 patients, there is no consensus on standard treatment. With the aims of reviewing the evidence supporting each of these therapeutic options, possibly reaching a consensus for treatment of PS2 patients affected by advanced NSCLC in clinical practice, and suggesting the priorities for clinical research in this field, an European Experts Panel took place in Avellino, Italy in April 2003. RESULTS: and conclusions On the basis of current evidence, chemotherapy treatment appears justified for patients with advanced NSCLC and PS2. Single-agent chemotherapy (gemcitabine, vinorelbine, taxanes) could be the preferred option, although carboplatin-based or low-dose cisplatin-based doublets may represent alternative options. Stronger evidence is expected from new clinical research specifically focused on PS2 patients. Single-agent chemotherapy should be the standard arm against which experimental treatments are tested in randomised trials dedicated to PS2 patients. High priority should be given to the evaluation of tolerability and efficacy of platinum-based combinations, and to the testing of new biological agents. Another research priority is the improvement of supportive care. Patients strongly need symptomatic improvement: end points such as symptom relief, clinical benefit and quality of life should have a central position in trials dedicated to PS2 NSCLC patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Avaliação de Estado de Karnofsky , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos como Assunto , Prova Pericial , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de NeoplasiasRESUMO
Thirty-four ovarian and breast cancer patients received autologous peripheral blood progenitor cell transplantation after high-dose myeloablative chemotherapy and either granulocyte-colony-stimulating factor (G-CSF) or granulocyte/macrophage-colony-stimulating fictor (GM-CSF) in the immediate post-transplant period. The recovery of T cell functionality was monitored by a three-color flow-cytometric approach using carboxyfluorescein diacetate succinimidyl ester, a probe the fluorescence intensity of which halves at each round of cell replication, in conjunction with CD3 and CD25 monoclonal antibodies. There was no significant difference between the two treatments on days 12, 20, and 40, T cell proliferation always being considerably lower than that of control cultures from healthy donors. At day 80, a significantly higher proportion of mitogen-stimulated T cells from GM-CSF-treated patients expressed interleukin-2 receptor, and a higher proportion of these T cells were actively proliferating. This phenomenon did not reflect any difference in the relative proportion of various lymphocyte subsets (T cells, CD4 and CD8+ T cells, CD45RA+ and CD45RO- T cells, and natural killer cells). At the end of follow-up (1-1.5 years) T cell proliferation had returned to values typically observed in healthy individuals in both groups of patients. Soon after transplantation (day 12), neutrophils from G-CSF-treated patients had a more elevated Fcgamma receptor I density and monocytes from GM-CSF-treated patients had a more elevated Fcgamma receptor II and MHC class II molecules density. The up-modulation of Fcgamma receptor II was maintained until day 40. Thus, administering G-CSF and GM-CSF in the post-transplant period affects T lymphocyte proliferation and phagocyte membrane molecules differently.