RESUMO
Tyrosine kinase inhibitors (TKIs) are very efficacious in non-small-cell lung cancer (NSCLC) patients harboring activating Epidermal Growth Factor Receptor (EGFR) mutations. However, about 10% of EGFR wild type (wt) patients respond to TKI, with unknown molecular mechanisms of sensitivity. We considered a case series of 34 EGFR wt NSCLC patients responsive to erlotinib after at least one line of therapy. Responsive patients were matched with an equal number of non-responsive EGFR wt patients. A panel of 26 genes, for a total of 214 somatic mutations, was analyzed by MassARRAY® System (Sequenom, San Diego, CA, USA). A 15% KRAS mutation was observed in both groups, with a prevalence of G12C in non-responders (80% vs. 40% in responders). NOTCH1, p53 and EGFR-resistance-related mutations were found more frequently in non-responders, whereas EGFR-sensitizing mutations and alterations in genes involved in proliferation pathways were more frequent in responders. In conclusion, our findings indicate that p53, NOTCH1 and exon 20 EGFR mutations seem to be related to TKI resistance. KRAS mutations do not appear to influence the TKI response, although G12C mutation is more frequent in non-responders. Finally, the use of highly sensitive methodologies could lead to the identification of under-represented EGFR mutations potentially associated with TKI sensitivity.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , Cloridrato de Erlotinib , Éxons , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Receptor Notch1/genética , Receptor Notch1/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismoRESUMO
BACKGROUND: To assess the efficacy and safety of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous non-small cell lung cancer (NSCLC) on the basis of the two registrative trials [ECOG E4599 trial and BO17704 (AVAiL) trial]. METHODS: A pooled analysis of the two trials was performed using a random effect model, and the results were summarized as number-needed-to-treat (NNT) and number-needed-to-harm (NNH). A 2-step analysis was performed. The primary analysis included only the patients treated with bevacizumab 15 mg/kg in the experimental arm, whereas the secondary analysis (with descriptive aim) included the patients treated with bevacizumab 15 mg/kg or those treated with bevacizumab 7.5 mg/kg in the experimental arm. The 1-year survival and 6-month progression-free rates were assumed as indexes of efficacy, and grade III-IV side effects were assumed as index of safety in both analyses. RESULTS: 1,921 patients were potentially eligible for the pooled analysis and were included in the secondary analysis, whereas 1,576 patients were included in the primary analysis. A large heterogeneity was documented for both 6-month progression-free interval (I(2) = 88.164%, p = 0.004) and overall survival (I(2) = 73.541, p = 0.052). The absolute risk reduction of 1-year death and 6-month progression were 3.3% (95% CI = -6.5 to 13.2%, p = 0.507), with a NNT = 30; and 15.2% (95% CI = 0.07-29.6%, p = 0.04), with a NNT = 6 (both in favor of the bevacizumab-containing regimens), respectively. The absolute risk of treatment-related death was 2.4% (95% CI = 0.8-3.9%, p = 0.003), with a NNH = 41 against the bevacizumab-containing regimens; that of bleeding was 3.3% (95% CI = 1.6-4.9%, p < 0.001), with a NNH = 30; that of hypertension was 6.6% (95% CI = 4.6-8.6%, p < 0.001), with a NNH = 15; that of proteinuria was 2.1% (95% CI = 0.3-3.8%, p = 0.024), with a NNH = 47; that of neutropenia was 7.3% (95% CI = 3.2-11.4%, p < 0.001), with a NNH = 13; that of thrombocytopenia was 1.5% (95% CI = 0.2-2.7%, p = 0.021), with a NNH = 66. No significant differences were observed in the efficacy and the safety analysis when all the patients treated with bevacizumab 7.5 mg/kg and 15 mg/kg were included into the pooled analysis. CONCLUSION: Adding bevacizumab to standard chemotherapy in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC seems to favor a modest improvement in the main outcomes, with a significant worsening of the safety profile. These data suggest caution in the generalized use of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC.
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Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Intervalo Livre de Doença , Esquema de Medicação , Medicina Baseada em Evidências , Hemorragia/induzido quimicamente , Humanos , Hipertensão/induzido quimicamente , Neutropenia/induzido quimicamente , Proteinúria/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
BACKGROUND: Non-small cell lung cancer (NSCLC) is the primary cause of cancer-related deaths worldwide. Epidermal Growth Factor Receptor (EGFR)-mutated patients usually benefit from TKIs treatment, but a significant portion show unresponsiveness due to primary resistance mechanisms. We investigated the role of TP53 mutations in predicting survival and response to EGFR-TKIs in EGFR-mutated NSCLC patients, to confirm, on an independent case series, our previous results. METHODS: An independent retrospective cohort study was conducted, on a case series of 136 EGFR-mutated NSCLC patients receiving first or second generation TKIs as a first line therapy, and a smaller fraction of patients who acquired the T790M resistance mutation and were treated with third generation TKIs in the second or further line of treatment. TP53 mutations were evaluated in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) of the patients. RESULTS: Forty-two patients (30.9%) showed a TP53 mutation. Considered together, TP53 mutations had no significant impact on time-to-event endpoints. Considering the different TP53 mutations separately, exon 8 mutations confirmed their negative effect on PFS (HR 3.16, 95% 1.59-6.28, p = 0.001). In patients who developed the T790M resistance mutation, treated with third generation TKIs, the TP53 exon 8 mutations predicted worse PFS (even though not statistically significant), and OS (HR 4.86, 95% CI: 1.25-18.90, p = 0.023). CONCLUSIONS: TP53 exon 8 mutations confirmed their negative prognostic impact in patients treated with first and second generation TKIs and demonstrated a role in affecting clinical outcome in patients treated with third generation TKIs.
RESUMO
OBJECTIVES: Considering the frequent expression of somatostatine receptors, we designed the G04.2011 trial to investigate the efficacy of the somatostatine analogue lanreotide in maintenance for SCLC patients after response to standard treatment. MATERIALS AND METHODS: A multicenter, randomized, phase 3 trial was conducted in SCLC expressing somatostatine receptors at baseline Octreoscan, responding after platinum-based chemotherapy with/without radiotherapy. Patients were randomized 1:1 to receive maintenance lanreotide 120 mg subcutaneously every 28 days, up to 1 year or progression versus observation. Randomization was stratified according to stage (limited/extended, LD/ED). The primary end-point was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. RESULTS: Seventy-one patients were randomly assigned (39 to lanreotide, 32 to observation) in 9 Italian institutions. Median PFS was 3.6 (95% CI 3.2-3.9) with lanreotide versus 2.3 months (95% CI 1.7-2.9) with observation (HR 1.51, 95% CI 0.90-2.50; P = 0.11). Stage was an independent predictor for PFS (HR 3.14, 95% CI 1.77-5.57; P < 0.0001). Median PFS was 7.0 (95% CI <1-13.5) with lanreotide versus 3.8 months (95% CI <1-8.6) with observation in LD (P = 0.21), and 3.0 (95% CI 2.2-3.8) versus 2.2 (95% 1.7-2.7) in ED (P = 0.19). Median OS was 9.5 (95% CI 4.8-14.3) with lanreotide versus 4.7 months (95% CI <1-16.6) with observation (P = 0.47). Treatment-related adverse events occurred in 28% of patients with lanreotide (grade 3 in two patients). CONCLUSION: Although survival outcomes were not significantly prolonged with lanreotide as a maintenance in SCLC expressing somatostatin receptors after response to standard treatment, lanreotide showed a slight PFS benefit in LD SCLC deserving further investigations.
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Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Peptídeos Cíclicos/uso terapêutico , Receptores de Somatostatina/genética , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética , Somatostatina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/efeitos adversos , Prognóstico , Modelos de Riscos Proporcionais , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Somatostatina/administração & dosagem , Somatostatina/efeitos adversos , Somatostatina/uso terapêutico , Resultado do TratamentoRESUMO
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.
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Adenocarcinoma/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Ensaios Clínicos Controlados como Assunto , Intervalo Livre de Doença , Seguimentos , Humanos , Metanálise como Assunto , Terapia Neoadjuvante , Recidiva Local de Neoplasia/prevenção & controle , Guias de Prática Clínica como Assunto , Cuidados Pré-Operatórios , Radioterapia/efeitos adversos , Neoplasias Retais/mortalidade , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Molecular diagnostics for non-small cell lung cancer (NSCLC) has become the standard of care for personalized treatment. Epidermal growth factor receptor (EGFR) mutation and EML4-ALK translocation represent the two most important alterations in first-line treatment decision-making. However, other potentially targetable alterations are also present. METHODS: One thousand consecutive NSCLC patients with EGFR wild type (wt) tumors diagnosed by routine molecular analysis were considered. KRAS, BRAF, ERBB2, PIK3CA, NRAS, ALK, MAP2K1, RET and DDR2 gene mutations were analyzed using the multiparametric Sequenom MassARRAY® platform. EML4-ALK and ROS1 rearrangements were also assessed by fluorescent in situ hybridization. HER4 status was determined by direct sequencing. RESULTS: Three hundred and forty-eight (34.8%), 31 (3.1%), 39 (4.4%), 14 (1.8%), 6 (0.7%), 16 (1.8%), 5 (0.6%) and 9 (0.9%) patients showed an alteration in KRAS, BRAF, ALK, ROS1, NRAS, PIK3CA, MAPK1/2 and HER2 genes, respectively. Of the 657 patients for whom all markers were determined, 318 (48%) patients had at least one alteration. Eight patients showed overlapping mutations, 4 KRAS mutation/EML4-ALK translocation, one KRAS mutation/ROS1 rearrangement, 2 KRAS/PIK3CA mutations, and one BRAF/PIK3CA mutations. CONCLUSIONS: About 50% of our patients had a potentially targetable alteration, confirming the usefulness of a multiparametric approach for routine molecular diagnostics aimed at identifying potential therapeutic targets.
RESUMO
An indirect comparison of cisplatin-pemetrexed (CP) and cisplatin-raltitrexed (CR) was performed. The Odds Ratios of 10, 15 and 20 month survival rate and response rate were assumed as indexes of efficacy; the Odds Ratio of grade III-IV side effects, and the absolute risk of overall, hematologic and non-hematologic toxicity, were assumed as indexes of safety. The outcomes of 352 patients were analysed. The Odds Ratios and 95% Confidence Interval (95% CI) of 10, 15 and 20 months survival rate and response rate were 1.2 (95% CI 0.65-2.24, p = 0.559), 1.02 (95% CI 0.49-2.12, p = 0.953), 1.13 (95% CI 0.44-2.91, p = 0.805) and 0.56 (95% CI 0.26-1.21, p = 0.141), respectively. An absolute increased risk of grade III-IV side effects was observed for CP: 6% (95% CI 3-9%, p < 0.001), 9% (95% CI 2-16%, p = 0.008) and 3% (95% CI 0-5%, p = 0.035) for overall, hematological and non-hematological toxicity. CP and CR can be considered comparable in terms of efficacy in the treatment of metastatic pleural mesothelioma, with a modest increased risk of grade III-IV side effects for CP.
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Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Humanos , Mesotelioma Maligno , Metanálise em Rede , Pemetrexede/administração & dosagem , Quinazolinas/administração & dosagem , Tiofenos/administração & dosagem , Resultado do TratamentoRESUMO
Purpose: To analyze the impact of TP53 mutations on response to first-line tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non-small cell lung cancer (NSCLC).Experimental Design: 136 EGFR-mutated NSCLC patients receiving first-line TKIs were analyzed. TP53 mutations were evaluated in 123 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).Results:TP53 mutations were observed in 37 (30.1%), 10 (27.0%), 6 (16.2%), 9 (24.3%), and 12 (32.4%) patients in exons 5, 6, 7, and 8, respectively. DCR was 70% in TP53-mutated patients compared with 88% in TP53-wild type (wt) patients [relative risk, RR, of disease progression: 3.17 (95% CI, 1.21-8.48), P = 0.019]. In particular, a 42% DCR was observed in patients with TP53 exon 8 mutation versus 87% in exon 8 wt patients [RR of disease progression 9.6 (2.71-36.63), P < 0.001]. Shorter median PFS and OS were observed in patients with TP53 exon 8 mutations compared with others (4.2 vs. 12.5, P = 0.058, and 16.2 vs. 32.3, P = 0.114, respectively); these differences became significant in the subgroup with EGFR exon 19 deletion (4.2 vs. 16.8, P < 0.001, and 7.6 vs. not reached, P = 0.006, respectively), HR 6.99 (95% CI, 2.34-20.87, P < 0.001) and HR 4.75 (95% CI, 1.38-16.29, P = 0.013), respectively.Conclusions:TP53 mutations, especially exon 8 mutations, reduce responsiveness to TKIs and worsen prognosis in EGFR-mutated NSCLC patients, mainly those carrying exon 19 deletions. Clin Cancer Res; 23(9); 2195-202. ©2016 AACR.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Proteína Supressora de Tumor p53/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Éxons/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Deleção de Sequência/genéticaRESUMO
BACKGROUND: Epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, and echinoderm microtubule-associated protein-like 4 (EML4) anaplastic lymphoma kinase (ALK) translocation are generally considered to be mutually exclusive. However, concomitant mutations are found in a small number of patients and the effect of these on response to targeted therapy is still unknown. PATIENTS AND METHODS: We considered 380 non-small-cell lung cancer (NSCLC) patients who underwent nonsequential testing for EGFR and EML4-ALK translocation. KRAS mutation analysis was also performed on 282 patients. RESULTS: We found 1.6%, 1.1%, and 2.5% of patients who showed a double mutation comprising EGFR and EML4-ALK, EGFR and KRAS, and EML4-ALK and KRAS, respectively. Twenty-eight patients with EGFR mutation underwent first-line therapy with a tyrosine kinase receptor; a clinical benefit was observed in 81.8% of patients with EGFR mutations only and in 67% of those who also showed an EML4-ALK translocation. Twelve patients with an EML4-ALK translocation received crizotinib and 7 of these had disease progression within 3 months (2 had a concomitant KRAS mutation and 1 had a concomitant EGFR mutation). Two patients showed stable disease, 1 of whom also had a KRAS mutation. Two patients obtained a partial response and 1 had a complete response; all harbored an EML4-ALK translocation only. The median overall survival of patients who carried an EML4-ALK translocation alone or concomitant with a KRAS mutation was 57.1 (range, 10.7-not reached) and 10.7 (range, 4.6-not reached) months, respectively. CONCLUSION: Concomitant EGFR, EML4-ALK, or KRAS mutations can occur in NSCLC. Concomitant KRAS mutation and EML4-ALK translocation represents the most common double alteration and confers a poor prognosis.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Mutação , Prognóstico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Malignant pericardial mesothelioma is an uncommon variety of a primary malignant cardio-pericardial tumor and it is a highly lethal and fortunately rare cardiac neoplasm. The presentation of pericardial mesothelioma is aspecific and pathologically mesothelioma is not the most common among primary tumors of the pericardium. It is characterized by atypical solid growth of mesothelium with formation of atypical cavities surrounded by fibrous stroma. Antemortem diagnosis is difficult and distant metastases are extremely rare. Radical surgery can be used to treat localized mesothelioma. The treatment for advanced primary pericardial mesothelioma is usually palliative because the tumor is resistant to radiotherapy and chemotherapy. The prognosis is unfavorable. The median survival from the onset of symptoms is six months. In this paper we report two cases of patients with primary mesothelioma of the pericardium without a definite history of asbestos exposure.
Assuntos
Neoplasias Cardíacas/patologia , Mesotelioma/patologia , Pericárdio/patologia , Adulto , Idoso , Diagnóstico Diferencial , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico , Humanos , Masculino , Mesotelioma/complicações , Mesotelioma/diagnóstico , Prognóstico , SobrevidaRESUMO
Although cisplatin and etoposide seem to represent the treatment of choice in Small-Cell Lung Cancer, a lot of data exist in literature supporting both the use of anthracycline-containing regimens and the use of alternating regimens where platinum-containing regimens and anthracycline-containing regimens are alternatively used as first line in the same patient. In our paper we review the outcomes of two different series of patients treated with ciclophosphamide-epidoxorubicin-etoposide (CEVP16) or carboplatin-etoposide (CBE) for extended Small-Cell Lung Cancer. Sixty-three patients (53.4%) were treated with CEVP16 and 55 patients (46.6%) with CBE. Response Rate (complete plus partial responses) was greater in patients treated with CEVP16 (49.2%) when compared with the response rate in patients treated with CBE (30.9%) (p=0.04 using the Chi-Square test); no differences were observed in the median time to progression (235 vs 199 days, using the Log-Rank test). Overall survival was greater in the CEVP16 group when compared with the CBE one (281 vs 208 days and 35.6% vs 16.3% of patients alive after 2 years of follow up for CEVP16 and CBE respectively, p=0.02 using the Log-Rank test). Although our data present all the methodological limits of the "case-series", it is interesting to observe how an anthracycline-containing regimen seems to be more effective than a platinum-containing one and how it could still play a role in the treatment of extended Small-Cell Lung Cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Cisplatino/uso terapêutico , Ciclofosfamida/uso terapêutico , Epirubicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Cisplatin-containing regimens represent the gold standard in the treatment of advanced non-small cell lung cancer, but carboplatin is often preferred for its better toxic profile when palliation is the aim of the treatment. The synergistic effect and tolerability of carboplatin-gemcitabine combination are well known. In this phase II trial, we evaluated the activity and safety of a schedule with carboplatin and gemcitabine, defined in our previous phase I trial. METHODS: Thirty-seven patients with measurable stage IV non-small cell lung cancer were treated with carboplatin, AUC 4.5 mg/ml/min on day 1, and gemcitabine, 800 mg/m2 on days 1 and 8, every 21 days. All patients were treated until disease progression or intractable toxicity and were evaluated before each course of chemotherapy for toxicity and after every 3 courses for response. RESULTS: After a median follow-up of over 10 months, complete response, partial response, and stabilization of the disease were observed in 3 (8.1%), 9 (24.3%), and 15 patients (40.5%), respectively. Median time to progression was 7 months. At this writing, 27 patients have died, with a median survival of 10 months, and 29 (78.3%), 16 (43.2%), and 11 (29.7%) patients are alive after 6, 12, and 15 months of follow-up, respectively. Toxicity was mild, and mainly hematological, with a significant correlation with the number of courses of chemotherapy (P = 0.0003). CONCLUSIONS: Our results are comparable with those reported in the literature and confirm the good activity and tolerability of the carboplatin-gemcitabine combination. Up to 4 courses of chemotherapy with carboplatin and gemcitabine may represent an interesting option in the palliative treatment of non-small cell lung cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Cuidados Paliativos/métodos , Idoso , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/secundário , Desoxicitidina/administração & dosagem , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: Although small-cell lung cancer is a chemosensitive malignancy, most patients rapidly relapse. Results of second-line treatment are generally poor. We conducted a phase II study to evaluate the activity and toxicity of a combination of gemcitabine and paclitaxel as second-line chemotherapy. PATIENTS AND METHODS: Eligible patients were refractory or relapsed small-cell lung cancer, with an Eastern Cooperative Oncology Group performance status of 0-2 and measurable disease. Paclitaxel was administered at 135 mg/m(2) days 1 and 8 immediately followed by gemcitabine at 1000 mg/m(2) every 3 weeks up to 6 courses. Restaging of disease was scheduled every 3 courses. RESULTS: Forty-one patients were enrolled. The median age was 65 years. Nineteen patients were considered refractory (progressive disease during or within 90 days from completion of first-line treatment), whereas 22 patients were chemotherapy sensitive. A total of 135 courses was administered (range, 1-6; median, 3). Nine patients achieved a partial remission (partial response, 22%), and 10 patients had stable disease (24%), with a disease control rate (partial response + stable disease) of 46%: in 12 (55%) of 22 patients who were sensitive and in 7 (37%) of 19 patients with refractory disease, respectively. All partial responses but one were observed in the sensitive group. The median duration of response was 5 months. The most-frequent severe toxicities were neutropenia grade 3-4 and neurologic grade 3 in 24% and 7% of delivered courses, respectively. CONCLUSIONS: The combination of gemcitabine and paclitaxel investigated in our study achieved a high disease control rate, but the schedule we adopted appeared to be quite toxic.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/induzido quimicamente , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , GencitabinaRESUMO
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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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Dor/tratamento farmacológico , Dor/etiologia , Cuidados Paliativos , Qualidade de Vida , Resultado do TratamentoRESUMO
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.
Assuntos
Antineoplásicos/uso terapêutico , Fibromatose Agressiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas , Quimioterapia Adjuvante , Fibromatose Agressiva/patologia , Fibromatose Agressiva/cirurgia , Humanos , Mesilato de Imatinib , Masculino , Metotrexato/administração & dosagem , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Resultado do Tratamento , Vimblastina/administração & dosagemRESUMO
BACKGROUND: Staging procedures used to detect metastatic breast cancer at the time of diagnosis are bone scan (BS), chest X-ray (CXR), liver ultrasonography (LUS) and laboratory parameters (LP). These procedures are expensive and not all patients need them. We aimed to identify groups of patients with different risks for metastatic disease. METHODS: We reviewed data from 1,218 consecutive cases of breast cancer. Pathological and biological parameters and instrumental procedures performed at the time of diagnosis and during 6 months of follow-up were recorded. True positive and negative, false positive and negative cases were evaluated. All cases were grouped on the basis of tumour size, nodal involvement, biological characteristics, menopausal status and age. RESULTS: We observed 46 (3.8%) true positive cases with metastatic disease at the time of diagnosis. Documentation relating to BS, CXR and LUS was available for 1,193, 1,206 and 1,206 patients, respectively, with 37 (3.1%), 8 (0.7%) and 10 (0.8%) true positive tests. Logistic regression analysis showed significant odds ratio estimates for pT status and nodal status, thus highlighting the role of these morphological data. These findings suggest that breast cancer patients can be divided into two subgroups: first group pT1-3N0-1. with < or = 3 involved nodes, and second group pT1-3N1 with > or = 4 involved nodes, pT4 and pN2 (metastases detection rate 1.46 and 10.68%, respectively). In the former group the appropriate procedures of staging would only be laboratory parameters, whereas in the latter group BS, CXR, LUS, LP and tumour markers CEA and CA 15.3 would.be necessary. CONCLUSIONS: The standard staging procedures to detect metastatic disease at breast cancer diagnosis require modification. On the basis of the literature data and our findings, the full staging procedure is appropriate in the second group of patients.