RESUMO
The effects of the short-term pre-operative administration of tamoxifen (TAM, 20 mg once daily) on the tumor levels of steroid receptors and the nuclear proliferation Ki-67 antigen, were investigated in 32 elderly patients with hormone-sensitive, operable primary breast cancer by means of fine-needle aspiration biopsy (FNAB). The FNAB smears before (pre-TAM) and after six weeks of treatment (post-TAM) were stained immunocytochemically in order to obtain an H-score for steroid receptors, and the percentage of cellular nuclei containing Ki-67. The mean oestrogen receptor (ER) score between the pre- and post-TAM specimens fell from 181.2 9.7 ( SEM) to 148.1 7.9 (Wilcoxon's matched-pairs signed-rank test, p=0. 01) and there was also a significant decrease in both the mean progesterone receptor (PgR) score (178.4 10.6 vs 148.5 10.6; p=0.01) and mean Ki-67 index (8.2% 1.2 vs 4.9% 0.9; p=0.0002). The reliability of FNAB as a sampling method was checked by comparing the results of the immunocytochemical assay (ICA) of the post-TAM biopsies with those of the immunohistochemical assay (IHA) of the corresponding excised tumors. There was a positive correlation between the ICA and IHA scores: ER (Spearman's correlation coefficient, rho=0.66, p<0.001), PgR (rho=0.84, p<0.001) and Ki-67 (rho=0.96, p<0.001). We conclude that the sequential use of FNAB is a reliable means of assessing the behaviour of within-tumor biomarkers during endocrine therapy.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Antagonistas de Estrogênios/uso terapêutico , Antígeno Ki-67/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Tamoxifeno/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/química , Feminino , Humanos , Imuno-HistoquímicaRESUMO
To investigate whether c-erbB 2 serum levels may be predictive of clinical response, progression-free and overall survival in postmenopausal women with advanced breast cancer hormonally treated, 265 patients enrolled in previous clinical trials were evaluated. C-erbB 2 serum levels were assessed before the start of treatment and in a subgroup of patients also at the first response evaluation. In addition, serum CA 15.3 levels were determined. The role of c-erbB 2 was investigated by means of multiple regression models in which both c-erbB 2 and CA 15.3 values were modelled as continuous variables together with other known prognostic factors. The failure probability tended to be higher in the presence of high c-erbB 2 levels, but the trend was not statistically significant; in contrast, significant results were obtained for progression-free survival (PFS,P <0.001) and overall survival (OS, P=0.014). The within-patient c-erbB 2 variation significantly predicted PFS (P=0.006) and OS (P=0.040). It is worth noting that c-erbB 2 and CA 15.3 baseline levels were significantly correlated and that the prognostic effect of c-erbB 2 tended to disappear in the presence of high CA 15.3 levels for PFS and OS.
RESUMO
AIMS AND BACKGROUND: At least half of the patients with squamous cell carcinoma of the esophagus (SCCE) present at diagnosis with metastatic disease, and most patients in a locally advanced phase will develop metastases despite potentially curative local therapy. Thus, the majority of patients with SCCE will become candidate for palliative chemotherapy. Only a few drugs have demonstrated moderate activity (>15%) against SCCE. The main purpose of this phase II trial was to assess the activity of vinorelbine, a semisynthetic vinca alkaloid with a wide spectrum of action, in advanced or relapsed SCCE. METHODS: Seventeen patients were included in the trial. Eleven of them had already received chemotherapy (cisplatin and fluorouracil) and/or radiotherapy at the time of the first diagnosis. All patients were treated with vinorelbine at the dose of 30 mg/m2 every two weeks. RESULTS: Sixteen of the 17 patients enrolled in the trial were assessable for activity: partial responses were observed in 4 of the 16 (25%), and 3 of them were pre-treated patients. A significant improvement of dysphagia was obtained in 4 of 11 symptomatic patients. Toxicity was mild, with only one episode of grade 4 neutropenia and constipation. CONCLUSIONS: In our experience, single-agent vinorelbine is active against SCCE. It was also active in patients previously treated with cisplatin and fluorouracil. The good tolerability and the possibility of relieving symptoms such as dysphagia strongly suggest the addition of vinorelbine to combination regimens with cisplatin as front-line chemotherapy for SCCE.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Vimblastina/análogos & derivados , Vimblastina/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , VinorelbinaRESUMO
Fluoropyrimidines remain the most important drugs in the treatment of breast and colorectal carcinoma, but response rates and survival time have been disappointing. Optimal administration is by continuous intravenous infusion, which makes it cumbersome to use and compromises patient independence. Recently, a number of new agents, including fluorouracil prodrugs and selective dihydropyrimidine dehydrogenase inhibitors, have been studied, with promising results. Capecitabine is the first in a new class of fluoropyrimidines. It is an oral, tumor-activated anticancer drug whose activity mimics that of continuously infused 5-fluorouracil. Capecitabine circumvents dihydropyrimidine dehydrogenase catabolism and appears to be at least as active against metastatic colorectal and breast cancer as conventionally administered intravenous 5-fluorouracil, with significantly less toxicity, an improved quality of life, and lesser cost. Capecitabine may ultimately provide enhanced antitumor activity to fluorouracil-containing regimes for advanced colorectal and breast cancer.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Pró-Fármacos/uso terapêutico , Animais , Antimetabólitos Antineoplásicos/química , Antimetabólitos Antineoplásicos/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina , Ensaios Clínicos como Assunto , Neoplasias Colorretais/radioterapia , Desoxicitidina/química , Desoxicitidina/metabolismo , Desoxicitidina/farmacologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Pró-Fármacos/farmacologia , Radioterapia Adjuvante , Análise de Sobrevida , Resultado do TratamentoRESUMO
Esophageal cancer is uncommon, but its incidence is rapidly increasing in the Western countries because of the high incidence of the cardia esophageal adenocarcinoma. Notwithstanding the encouraging results achieved with surgical procedures, esophageal carcinoma has a poor prognosis with 5-year survival in 10% of cases without differences between both squamous and adenocarcinoma histologies. Almost 50% of esophageal cancer patients have unresectable disease at presentation; in the past years combined modality treatments, using chemotherapy and/or radiotherapy with or without surgery, have been evaluated to reduce the risk of local and/or distant recurrences. Ongoing regimens with new agents (Taxanes, Vinorelbine, Irinotecan), in association or not with platinum compounds, show good antitumor efficacy and tolerability, even in the metastatic disease. Preoperative strategies with radiation only did not give any advantage compared to surgery alone, instead, controversial results were obtained, with a minimal advantage, using chemotherapy. Combined chemotherapy and radiation, in suitable candidates for resection has shown an improvement of complete pathological responses, in both the histologies, but with superior toxicities when compared to chemotherapy or radiation therapy alone. Postoperative adjuvant therapies as radiation, chemotherapy or both, have not led to a marked improvement in overall survival and should be performed only in clinical trials. The use of chemoradiotherapy showed a clear advantage versus radiotherapy alone and in many cases equivalent to regimens plus surgery even if control studies haven't been performed. Clinical trials with novel biologic agents, in combination to chemotherapy or alone, against cell growth arrest, neoagiongenesis and tumor metastasis invasion process are currently under evaluation. In the coming years new markers as antigen Ki-67 determination, p53 mutation or high levels activity of thymidylate synthase and novel staging techniques as PET could be precious to identify the better treatment for each patient.
Assuntos
Neoplasias Esofágicas/terapia , Terapia Combinada , Neoplasias Esofágicas/patologia , Humanos , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , PrognósticoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Fertilidade/efeitos dos fármacos , Adulto , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Menopausa , Metotrexato/administração & dosagem , Gravidez , Estudos Retrospectivos , Risco , Resultado do TratamentoRESUMO
BACKGROUND: Response and survival in patients with advanced or metastatic nonsmall cell lung carcinoma (NSCLC) remain poor. As single agents, the nucleoside analog gemcitabine, and the semisynthetic vinca alkaloid vinorelbine, have been shown to be effective in NSCLC and to have a low toxicity profile. METHODS: Fifty-four chemotherapy-naive patients with NSCLC Stage IIIB (any TN3M0 or T4 any NM0) or IV (any T any NM1) were enrolled in this single-institution Phase II study. Gemcitabine 1250 mg/m(2) and vinorelbine 25 mg/m(2) were both administered on Days 1 and 8 every 3 weeks for up to 9 courses unless disease progression or severe toxicity required their discontinuation. RESULTS: Partial tumor regression was observed in 16 patients, for an overall response rate of 30% (95% confidence interval, 18.4-46.7%) on an intent-to-treat basis. The median time to progression was 5 months (range, 3-20). The median survival was 12 months (range, 5-42+); 1-year and 2-year survival rates were 49.1% and 17%, respectively. Hematologic toxicity was mild with only 11% of the patients developing Grade 3 neutropenia. None of the patients developed any Grade 4 toxicity. CONCLUSIONS: The combination of gemcitabine plus vinorelbine is feasible on an outpatient basis. The good activity and tolerability of the regimen make it a suitable candidate for further trials, using platinum-based regimens as comparators and possibly selecting elderly and less fit patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vinorelbina , GencitabinaRESUMO
The aim of the present study was to evaluate the clinical activity and side effects of a combination chemotherapy consisting of a five-day continuous infusion of fluorouracil and i.v. vinorelbine in metastatic previously treated breast cancer patients. The patient population was represented by 28 women with evaluable disease, previously subjected to chemotherapy, including anthracycline-containing regimens in 89% of patients. Treatment consisted of five-day infusion of 700 mg/m2/day of fluorouracil and vinorelbine, 20 mg/m2 i.v. bolus on day 1 and 6. In the absence of Grade > 3 leukopenia and stomatitis, cycles were repeated every three weeks, for a total of six cycles. Four complete and thirteen partial responses were documented, accounting for a response rate of 61% (95% CI: 40.5-78.5); the clinical efficacy was high even in patients unresponsive to prior anthracycline treatment. The median response duration calculated from the first drug injection was 8 months (range 4-11). Treatment was well tolerated, with 4% Grade 4 stomatitis and 20% Grade 3 leukopenia as the main toxic reactions. This drug combination is active in metastatic previously treated breast cancer patients, is devoid of severe side effects, and warrants further testing.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas , Injeções Intravenosas , Leucopenia/induzido quimicamente , Pessoa de Meia-Idade , Estudos Prospectivos , Terapia de Salvação , Estomatite/induzido quimicamente , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , VinorelbinaRESUMO
BACKGROUND: To explore the activity and tolerability of gemcitabine (GEM) and carboplatin (CBDCA) in non-small-cell lung cancer (NSCLC) we tested four administration sequences on H460 NSCLC cells, and at the same time performed a randomized phase II trial using analogous schedules. PATIENTS AND METHODS: GEM was given first in two in vitro sequences, and CBDCA first in the other two; interaction was quantified calculating a combination index. Eighty-eight chemotherapy-naïve, stage IV NSCLC patients were randomly assigned to receive either: GEM (1000 mg/m(2)) on days 1 and 8 and CBDCA (AUC 5 mg.min/ml) on day 1, 4 h before GEM (arm A); same as arm A except CBDCA given 4 h after GEM (arm B); GEM on days 1 and 8 and CBDCA on day 2 (arm C); GEM on days 2 and 9 and CBDCA on day 1 (arm D). Courses were repeated every 21 days. RESULTS: In the preclinical study, CBDCA given before GEM produced a synergistic cytotoxic effect. Two complete and 29 partial responses occurred in 86 of 88 treated patients (intention-to-treat analysis 35%; 95% confidence interval 25.5% to 46.8%). One- and 2-year survivals were 44% and 11%, respectively. Grade 3/4 thrombocytopenia occurred in 11%; grade 3/4 neutropenia in 17%; and non-hematological toxicity was insignificant. Median survival was 11 months (range 7-18+), but better in patients receiving CBDCA first (arms A and D) (13 versus 9 months) than in patients receiving GEM first (arms B and C). The response was greater (50% versus 31%) in arm A than in the other arms. CONCLUSIONS: The CBDCA/GEM combination is safe and active against stage IV NSCLC. Our preclinical and clinical findings suggest that administration of CBDCA before GEM gives the better outcome.