RESUMO
BACKGROUND: In the Phase III 'GRETA' trial 474 women aged ≥70 years with early breast cancer were randomly assigned to surgery plus tamoxifen for 5 years or tamoxifen alone for 5 years. This is a long-term update. PATIENTS & METHODS: Focusing on patients still alive in 2003, outcome end points has been recalculated. RESULTS: Median distant metastases disease-free survival is longer with tamoxifen alone for 5 years; (48.8 vs 37.9 months; p = 0.009). No difference was found in distant metastases rate, disease-free survival, breast cancer and overall survival. CONCLUSION: Primary endocrine treatment until the the best response, followed by minimal surgery and prosecution endocrine treatment for 5-10 years is a suitable option for elderly breast cancer patients. Delayed surgery does not prejudice overall survival.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Tamoxifeno/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia. METHODS: From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (N = 478) were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing. RESULTS: Overall, KRAS tumour mutation rate was 30% (145/478 positive cases). Distribution of mutation carriers was surprisingly different within the island: 87/204 (43%) in North Sardinia vs. 58/274 (21%) in Middle-South Sardinia (p<0.001). Among 384 CRC cases whose DNA was available, only one (0.3%) patient carried a mutation in BRAF gene; PIK3CA was found mutated in 67 (17%) patients. A significant inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 19/183 (10%) cases from northern vs. 48/201 (24%) cases from central-southern island (p<0.001). This heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy. CONCLUSIONS: Our findings support the hypothesis that differences in patients' origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes.
Assuntos
Neoplasias Colorretais/genética , Genes ras , Genética Populacional , Mutação , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas B-raf/genética , Sequência de Bases , Classe I de Fosfatidilinositol 3-Quinases , Primers do DNA , Feminino , Humanos , Itália , Masculino , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: Breast cancer patients with >3 involved nodes (N+) have a poor outcome. Chemotherapy (CT), alone or combined with endocrine therapy (ET) in hormone receptor (HOR)-positive patients, is the standard for these women. However, there are still questions surrounding the optimal adjuvant CT regimen. METHODS: 244 patients with >3 N+ were randomized to receive either four 3-weekly courses of epirubicin (E: 100 mg/m(2), day 1) followed by four 4-weekly cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF: 600, 40, 600 mg/m(2), days 1, 8: n = 122) or four 3-weekly courses of paclitaxel (T: 175 mg/m(2), day 1) followed by four 3-weekly cycles of epirubicin and vinorelbine (E: 75 mg/m(2), day 1; V: 25 mg/m(2), days 1, 8: n = 122). After CT, tamoxifen (plus an LH-RH analog in menstruating women) was given to all HOR-positive patients over a period of 5 years. Overall survival (OS) was the primary end point. Relapse-free survival (RFS) and toxicity were secondary end points. RESULTS: At a median follow-up time of 102 months (range 3-146), OS and RFS did not differ significantly between groups (E-CMF vs. T-EV: OS, HR 0.94, 95% CI 0.59-1.48, p = 0.8; RFS, HR 0.86, 95% CI 0.57-1.29, p = 0.45). The lack of any difference between assigned treatments was confirmed by multivariate analysis (E-CMF vs. T-EV: RFS, HR 0.98, 95% CI 0.64-1.48, p = 0.9). The 2 regimens showed different toxicity profiles. In fact, significantly more women assigned to E-CMF were affected by stomatitis (p = 0.001) while significantly more women in the T-EV group developed peripheral neuropathy (p < 0.0001) and musculoskeletal disorders (p < 0.0001). However, side effects were moderate and manageable and no toxic death occurred in either arm of the study. CONCLUSIONS: T-EV was safe and moderately toxic but was not superior to E-CMF.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Epirubicina/administração & dosagem , Fluoruracila/administração & dosagem , Metotrexato/administração & dosagem , Paclitaxel/administração & dosagem , Vimblastina/análogos & derivados , Adulto , Idoso , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Resultado do Tratamento , Vimblastina/administração & dosagem , VinorelbinaRESUMO
BACKGROUND: In recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated. METHODS: Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test. RESULTS AND CONCLUSION: Overall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764_8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations.
Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Mutação , Idoso , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Saúde da Família , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , RecidivaRESUMO
BACKGROUND: Polycystic liver disease (PLD) is a rare, congenital, benign condition characterized by the presence of multiple bile-duct-derived epithelial cysts in the liver parenchyma. The disease is usually asymptomatic, but cyst growth can result in complications such as ascites, esophageal varices, jaundice and hepatic failure. The exact mechanism leading to cyst growth is unclear, but estrogenic stimulation and paracrine action of vascular endothelial growth factor (VEGF) are thought to play a role in the growth of cyst epithelium. CASE REPORT: We report a case of acute liver failure in a young woman with PLD and liver metastases from breast carcinoma. RESULTS: No data are available in the literature about metastatic liver involvement in PLD patients affected by breast cancer. The prognosis of patients with liver metastases is generally poor but fulminant liver failure is a very rare occurrence. Estrogen stimulation seems to be a risk factor for breast cancer and severe PLD. In the reported case, the presence of either the cysts or the metastatic lesions may have resulted in more extensive liver damage. CONCLUSIONS: The adoption of drugs selected in relation to their hepatic toxicity together with careful monitoring of liver function is warranted in the management of breast cancer patients affected by PLD, in order to reduce the risk of liver failure.
Assuntos
Neoplasias da Mama/secundário , Hepatopatias/complicações , Falência Hepática Aguda/etiologia , Neoplasias Hepáticas/secundário , Adulto , Antineoplásicos/uso terapêutico , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/terapia , Terapia Combinada , Cistos/etiologia , Cistos/patologia , Feminino , Humanos , Hepatopatias/fisiopatologia , Falência Hepática Aguda/patologia , Falência Hepática Aguda/fisiopatologia , Neoplasias Hepáticas/fisiopatologia , Mastectomia , RadioterapiaRESUMO
Conventional imaging procedures have proved of limited value in assessing tumor response to neoadjuvant chemotherapy in locally advanced primary breast cancer (LAPBC). We evaluated the usefulness of radioisotopic procedures comparing planar scintimammography (SM) to SPECT, monitoring pre-surgery neoadjuvant chemo- or hormonotherapy response in 32 LAPBC patients. In all cases, 99mTc-tetrofosmin conventional planar SM and SPECT were acquired by dual-head gamma camera with HR parallel hole collimators. In 15 cases, planar SM with small field of view high resolution dedicated breast camera (DBC) was also acquired. Scintigraphic data always correlated with histopathological findings. At surgery, 4/32 patients had pathological complete remission (pCR), while 28/32 patients had residual tumors. Both conventional planar SM and SPECT were true negative in 4/4 (100%) pCR patients, as was DBC in the only studied case. Conventional planar SM and SPECT detected residual tumors in 23/28 (82%) and in 25/28 (89.2%) cases, respectively. Both procedures missed 2 multifocal, scattered microscopic residues, only evidenced at DBC. Conventional planar SM also missed 3 further macroscopic residues (15-20 mm), while SPECT only one of these, a mucinous BC, in which DBC was not performed. DBC correctly classified all other 12 patients in whom the procedure was performed. Both conventional planar SM and SPECT proved useful diagnostic tools in monitoring neoadjuvant chemo/hormono therapy response in LAPBC with SPECT appearing more sensitive; however, our data, although in a limited number of cases, suggest that sensitivity can further be increased using high resolution DBC, especially in detecting microscopic residual tumor foci.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Mamografia , Terapia Neoadjuvante , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstadienos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/tratamento farmacológico , Feminino , Humanos , Linfonodos/patologia , Programas de Rastreamento , Pessoa de Meia-Idade , Compostos Organofosforados , Compostos de Organotecnécio , Prognóstico , Compostos Radiofarmacêuticos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Primary chemotherapy as part of multidisciplinary approach is the established treatment for inoperable stage III B breast cancer. The primary endpoints were conversion to operable disease and feasibility of conservative surgery (breast-conserving therapy: BCT); secondary were clinical and pathological complete response rate, local and distant control and safety of the primary regimen. METHODS: Between 1998 and 2001, 40 inoperable breast cancer patients < or =60 years, 72% T4abc and 28% T4d, received 6 cycles of primary PEV dose-dense regimen: cisplatin 50 mg/m2, epirubicin 100 mg/m2 and vinorelbine 25 mg/m2, i.v. (q 14). Modified radical mastectomy (MRM) or BCT was performed, followed by adjuvant chemotherapy, radiotherapy and hormone therapy. RESULTS: All patients were converted to operable disease, and BCT was feasible in 24% of T4abc patients. After a median follow-up of 84 months (range 58-96), local and distant relapses were 7.5% (0% in BCT ) and 25% (25% in BCT), respectively. Clinical response was 80% (clinical complete response [cCR]: 20%); pathological complete response (pCR) was 40% in breast, 50% in axilla (pLN0); 32% both in breast and axilla. Neutropenia (G4, 30%), leukopenia (G4, 25%), alopecia (G2, 100%), nausea and vomiting (G4, 20%) were the most common toxicities. CONCLUSIONS: The PEV dose-dense regimen seems to be highly effective in terms of resectability and pCR. Toxicity, mainly hematological, was acceptable. Successful BCT is feasible, in selected patients, without compromising local and distant control.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Epirubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: The BRCA2-8765delAG mutation was firstly described in breast cancer families from French-Canadian and Jewish-Yemenite populations; it was then reported as a founder mutation in Sardinian families. We evaluated both the prevalence of the BRCA2-8765delAG variant in Sardinia and the putative existence of a common ancestral origin through a haplotype analysis of breast cancer family members carrying such a mutation. METHODS: Eight polymorphic microsatellite markers (D13S1250, centromeric, to D13S267, telomeric) spanning the BRCA2 gene locus were used for the haplotype analysis. Screening for the 8765delAG mutation was performed by PCR-based amplification of BRCA2-exon 20, followed by automated sequencing. RESULTS: Among families with high recurrence of breast cancer (> or = 3 cases in first-degree relatives), those from North Sardinia shared the same haplotype whereas the families from French Canadian and Jewish-Yemenite populations presented distinct genetic assets at the BRCA2 locus. Screening for the BRCA2-8765delAG variant among unselected and consecutively-collected breast cancer patients originating from the entire Sardinia revealed that such a mutation is present in the northern part of the island only [9/648 (1.4%) among cases from North Sardinia versus 0/493 among cases from South Sardinia]. CONCLUSION: The BRCA2-8765delAG has an independent origin in geographically and ethnically distinct populations, acting as a founder mutation in North but not in South Sardinia. Since BRCA2-8765delAG occurs within a triplet repeat sequence of AGAGAG, our study further confirmed the existence of a mutational hot-spot at this genomic position (additional genetic factors within each single population might be involved in generating such a mutation).
Assuntos
Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Deleção de Genes , Predisposição Genética para Doença/genética , Proteínas Reguladoras de Apoptose , Neoplasias da Mama/metabolismo , Canadá/etnologia , Etnicidade , Feminino , França/etnologia , Genética Populacional , Haplótipos , Humanos , Israel/etnologia , Itália/epidemiologia , Judeus/genética , Masculino , Linhagem , Repetições de Trinucleotídeos , Iêmen/etnologiaRESUMO
Esophageal cancer (EC) is a highly lethal disease. Approximately 50% of patients present with metastatic EC and most patients with localized EC will have local recurrence or develop metastases, despite potentially curative local therapy. The most common sites of distant recurrence are represented by lung, liver and bone while brain and breast metastases are rare. Usually patients with advanced disease are not treated aggressively and their median survival is six months. We report a woman patient who developed breast and brain metastases after curative surgery. We treated her with a highly aggressive chemotherapeutic and surgical combination resulting in a complete remission of the disease even after 11-year follow-up. We think that in super selected patients with more than one metastasis, when functional status is good and metastases are technically resectable, a surgical excision may be considered as a salvage option and chemotherapy should be delivered to allow a systemic control.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/cirurgia , Neoplasias da Mama/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/secundário , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/secundário , Cisplatino/administração & dosagem , Terapia Combinada , Neoplasias Esofágicas/patologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/terapia , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Osteopetrosis or Albers-Schönberg's disease is a heterogeneous group of rare hereditary troubles of the bone characterized by bone sclerosis due to an alteration of the bone reabsorption mediated by osteoclasts. The defect in the osteoclastic activity is responsible for complete or partial medullary cavities occlusion, with consequent reduced hemopoiesis, and for the excessive fragility of the affected bone segments. CASE REPORT: We reported the case of a young man of 31 years affected by osteopetrosis in which a small cell lung cancer developed. RESULTS: Small cell lung cancer is a particularly rare neoplasm in the young, and even though it is highly sensitive to chemotherapeutic treatment its prognosis remains poor. The greatest clinical problem connected with chemotherapeutic treatment of patients affected by osteopetrosis is the variability of the reduction of their bone marrow reserve, which could expose them to an excessive hematological toxicity caused by the therapy. CONCLUSIONS: The adoption of suitable prophylactic measures, such as the use of growth factors and drugs selected in relation to their toxicity or given in reduced doses, should be appropriately considered in these subjects.
Assuntos
Carcinoma de Células Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Osteopetrose/complicações , Adulto , Biópsia , Carcinoma de Células Pequenas/complicações , Carcinoma de Células Pequenas/diagnóstico por imagem , Carcinoma de Células Pequenas/patologia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Osteopetrose/diagnóstico por imagem , Osteopetrose/patologia , RadiografiaRESUMO
PURPOSE: To investigate the value of the addition of either cisplatin (CDDP) or lonidamine (LND) to epirubicin (EPI) in the first-line treatment of advanced breast cancer. PATIENTS AND METHODS: Three hundred seventy-one metastatic breast cancer patients with no prior systemic chemotherapy for advanced disease were randomized to receive either EPI alone (60 mg/m(2) on days 1 and 2 every 21 days), EPI and CDDP (30 mg/m(2) on days 1 and 2 every 21 days), EPI and LND (450 mg orally daily, given continuously), or EPI, CDDP, and LND. Time to progression, response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study. RESULTS: The groups were well balanced with respect to prognostic factors. Time to progression did not differ in the comparison between CDDP arms and non-CDDP arms (median, 10.9 months v 9.4 months, respectively; P =.10) or between that of LND arms and non-LND arms (median, 10.8 months v 9.9 months, respectively; P =.47), nor did overall survival. The response rate did not significantly differ in the comparison between LND arms and non-LND arms (62.9% v 54.0%, P =.08). No difference in treatment activity was observed between CDDP arms and non-CDDP arms. Toxicity was significantly higher in the CDDP arms, leading to CDDP dose adjustment in 40% of cases. The most frequent side effects were of a hematologic and gastrointestinal nature. The addition of LND produced more myalgias and fatigue. CONCLUSION: Neither CDDP nor LND was able to significantly improve the time to progression obtained by EPI. CDDP, however, significantly worsened the drug's tolerability.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/patologia , Cisplatino/administração & dosagem , Progressão da Doença , Epirubicina/administração & dosagem , Feminino , Humanos , Indazóis/administração & dosagem , Modelos Logísticos , Pessoa de Meia-Idade , Análise de SobrevidaRESUMO
From September 2001 to November 2002, 35 patients aged 70-81 (median, 75) years, with measurable metastatic lesions from colorectal carcinoma, were treated with a combination of oxaliplatin (OXA) infused i.v. over 2 h on day 1, and capecitabine, assumed orally twice a day (12-h apart) from day 2 to day 15. An alternated dose escalation for both drugs was planned over the first three cycles for each patient, in the absence of WHO grade > or =2 toxicity on previous cycle: starting doses were 85 mg/m2 for OXA, and 2000 mg/m2 (day) for capecitabine on first cycle; on second cycle, OXA was planned at 100mg/m2, while capecitabine was planned at 2500 mg/(m2 day) on third cycle. Treatment was repeated every 3 weeks until progression, or for a maximum of 12 cycles. A total of 212 cycles were administered, with a median of 6 (range, 1-12) cycles/patient. Dose escalation was performed in 18 (51%) patients for OXA, and in 4 (11%) patients for capecitabine. No grade 4, and 10 (29%) cases of grade 3 toxicity of any type were reported. Abdominal symptoms (pain, nausea, or vomiting) affected 66% of patients, but they were of grade 3 in only 2 (6%) patients. Grade 3 diarrhoea occurred in 3 (9%) patients. Two complete and 12 partial responses (PR) were reported, for an overall response rate of 40% (95% CI, 24-58%). Progression of disease occurred in 23 (66%) patients, and 18 (51%) died. The actuarial median progression-free and survival time were 6.9 and 14.1 months, respectively.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Desoxicitidina/análogos & derivados , Metástase Neoplásica/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina , Neoplasias Colorretais/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fluoruracila/análogos & derivados , Humanos , Itália , Masculino , Dose Máxima Tolerável , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Análise de Sobrevida , Resultado do TratamentoRESUMO
We investigated the activity and toxicity of a combination of vinorelbine 25 mg/m2 on days 1 and 15; epirubicin 25 mg/m2 on days 1, 8, 15; and 5-fluorouracil continuous infusion at 200 mg/m2 every day, administered as first-line chemotherapy in anthracycline-naive metastatic breast cancer patients. Fifty-three patients entered the study. Cycles were repeated every 28 days. Objective response was 60% by World Health Organisation (WHO) criteria and 63% by Response Evaluation Criteria in Solid Tumours (RECIST). The median time to progression was 12.7 months (17.6 months in responders) and the median survival duration was 32.9 months. The dose-limiting toxicity was leucopenia (grade 3/4 in 36% of patients). Grade 3/4 non-haematological toxicities included mucositis in 11% of patients, skin and cardiac toxicity in 4% and 2%, respectively. The combination of vinorelbine, epirubicin and 5-fluorouracil continuous infusion was found to be an active and manageable first-line regimen for metastatic breast cancer patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalos de Confiança , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , VinorelbinaRESUMO
BACKGROUND: A biweekly regimen of irinotecan 200 mg/m2 on day 1 and levo-leucovorin (LV) 250 mg/m2 plus 5-fluorouracil (5-FU) 850 mg/m2 via intravenous bolus on day 2 was assessed in 2 consecutive randomized trials in metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Individual data of 254 patients were merged, and baseline features potentially affecting overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of severe toxicity were analyzed by univariate and multivariate analyses. RESULTS: In the pooled series, ORR was 33% (95% confidence interval [CI], 27%-39%). Liver-only disease (47% vs. 25%; P=0.0012) and absence of previous weight loss (38% vs. 20%; P=0.0189) were significantly associated with a higher ORR on the multivariate analysis. Absence of weight loss (hazard ratio, 1.40; 95% CI, 1.02-1.93; P=0.0377) was significantly associated with a longer PFS (7.5 months vs. 6 months). Median OS was 15.1 months (95% CI, 13.5-16.6 months). Primary surgery, good performance status (PS), only one metastatic site, and oxaliplatin-based second-line treatment independently predicted a longer OS. Grade 4 neutropenia was significantly associated with a PS>or=1, whereas risk of grade>or=3 diarrhea was directly related to age and previous weight loss. CONCLUSION: Patients with no weight loss and/or preserved PS and with a limited disease extent appeared to obtain the greatest benefit from our irinotecan/5-FU/LV regimen, with acceptable toxicity. Notably, the regimen was effective and well tolerated by elderly patients. This regimen may represent the rationale for assessing the addition of novel antiangiogenic drugs to the treatment of metastatic CRC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Injeções Intravenosas , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento , Redução de PesoRESUMO
BACKGROUND: To assess the activity and toxicity of primary chemotherapy with epirubicin (60 mg/m2 every other week) and vinorelbine (25 mg/m2, weekly) plus granulocyte colony-stimulating factor (G-CSF) for 12 weeks, in patients with locally advanced breast cancer in a multicenter setting. PATIENTS AND METHODS: Patients with stage IIIA or IIIB breast cancer, not older than 70, were eligible. A two-stage phase II design was applied. Response was assessed clinically, instrumentally and pathologically. RESULTS: Out of 48 enrolled patients, 87.5% received all planned cycles, with a median dose-intensity of 30 mg/m2/week for epirubicin and 23.8 mg/m2/week for vinorelbine. A clinical or instrumental objective response was reached in 42 patients (87.5%, exact 95% CI: 74.7-95.3); significant downstaging was reached in all but one patient; 6 cases had a pathological complete response in the breast, and 2 cases in the lymph nodes too (pathological complete response rate 4.2%, exact 95% CI: 0.5-14.2); a further 2 patients had only microscopic cancer foci at pathological examination of the breast. Radiological tests underestimated the treatment effect on the breast. Toxicity was mild, neutropenia being the most frequent (grade 3-4 in 47% of patients), but never complicated with fever or sepsis. Mild constipation (< or =grade 2) occurred in 35% of patients. Moderate to severe asthenia occurred in 12% of 6 patients. No cardiac toxicity was reported. At 3 years, disease-free survival was 68% and overall survival 81%. CONCLUSION: Primary chemotherapy with epirubicin every other week, weekly vinorelbine and G-CSF support is highly active and well tolerated in patients with locally advanced breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Epirubicina/administração & dosagem , Vimblastina/análogos & derivados , Vimblastina/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Mastectomia , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Taxa de Sobrevida , VinorelbinaRESUMO
To evaluate the usefulness of 99mTc-tetrofosmin (TF) SPECT in the detection of intrathoracic malignant lesions, we studied 304 patients, 261 with malignant and 43 with benign lesions; 196 of the former had non-treated primary tumors, 193 lung cancer (LC) and 3 mesotheliomas, 11 had LC recurrences and 54 had metastases from different kinds of tumors. Twenty-nine patients with primary tumors were re-checked after chemotherapy or surgery. In all patients, after 740 MBq TF injection, both planar and SPECT images were acquired and analysed qualitatively, SPECT images also semiquantitatively. Scintigraphy was always compared to CT. SPECT showed higher sensitivity, specificity and accuracy values than CT (98.1, 90.7 and 97 vs. 96.2, 81.4, and 93.9%, respectively), their combined use achieving 100% sensitivity and 98.8% accuracy. Planar did not give more information than SPECT, showing a significantly lower sensitivity (63.2%) and accuracy (67.4%). SPECT showed higher accuracy values than CT and planar (86.9 vs. 78.3 and 69.6%) in NSCLC mediastinal lymph node staging. Moreover, SPECT was concordant with CT in correctly evaluating the response to chemotherapy or surgery in all monitorized primary tumors cases, except in one in whom only SPECT detected residual tumor. The semiquantitative analysis added useful information in differentiating malignant from benign lesions and in monitoring the response to chemo-therapy. TF SPECT appears a highly accurate diagnostic method in the detection of intrathoracic malignant lesions, in lungs and pleura, as well as in NSCLC mediastinal lymph node staging and in monitoring treatment effectiveness, playing a complementary role to CT in selected cases.
Assuntos
Compostos Organofosforados , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Neoplasias Torácicas/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Terapia Combinada , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Pneumopatias/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Mesotelioma/diagnóstico por imagem , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasia Residual , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , Neoplasias Pleurais/cirurgia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Neoplasias Torácicas/tratamento farmacológico , Neoplasias Torácicas/patologia , Neoplasias Torácicas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
We evaluated the usefulness of 99mTc-tetrofosmin (TF) scintigraphy in monitoring chemotherapy response in 31 inoperable lung cancer (LC) patients, 24 NSCLC and 7 SCLC. In all cases after 740 MBq 99mTc-TF i.v. injection both planar and SPECT images were acquired, before and after 3 cycles of chemotherapy; SPECT was analysed both qualitatively and semiquantitatively by calculating tumor/background ratio (T/B). Scintigraphic data were always related to CT findings, according to which patients were classified into 2 groups after therapy: responders (with >or=50% reduction in tumor size) and non-responders (with an increase or no change/no significant reduction in tumor size). Four patients were rechecked for the third time, during long-term follow-up. SPECT images, positive before therapy in all cases, were concordant with CT in assessing treatment response in 13/13 responders and in 18/18 non-responder patients, showing tumor reduction in the former and an increase or no change/no significant reduction in the latter. Planar imaging failed to give additional information but also led to disease down-staging in some cases. T/B ratio significantly decreased after therapy (1.67+/-0.39 vs. 3.02+/-0.87, p<0.005) in responders Assuntos
Neoplasias Pulmonares/tratamento farmacológico
, Neoplasias Pulmonares/patologia
, Compostos Organofosforados
, Compostos de Organotecnécio
, Compostos Radiofarmacêuticos
, Tomografia Computadorizada de Emissão de Fóton Único/métodos
, Idoso
, Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
, Carcinoma Pulmonar de Células não Pequenas/patologia
, Carcinoma de Células Pequenas/tratamento farmacológico
, Carcinoma de Células Pequenas/patologia
, Linhagem Celular Tumoral
, Progressão da Doença
, Feminino
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Tomografia Computadorizada por Raios X
, Resultado do Tratamento
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Neoplasias Pulmonares/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/cirurgia , Terapia Combinada , Cistectomia/métodos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Evolução Fatal , Humanos , Achados Incidentais , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/cirurgia , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , GencitabinaRESUMO
Among primary liver cancers occurring worldwide, hepatocellular carcinoma (HCC) is the major histological type accounting for 70-85% of all cases. Phase III trials in patients with advanced HCC treated with sorafenib (SO), a multitargeted tyrosine kinase inhibitor, showed significant improvements in both overall and progression-free survival. We report the cases of two elderly patients with advanced HCC who had prolonged stable disease following treatment with SO (400 mg bid). Patient 1 was treated with SO for a period of 16 months until evidence of right sacral metastases was noted. Patient 2 received SO 400 mg bid from January 2009 to October 2009 until radiological evidence of disease progression was noted. Both patients experienced minimal toxicity, suggesting that SO can be safely administered to elderly patients.