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1.
ESMO Open ; 6(5): 100254, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34481329

RESUMO

BACKGROUND: The advanced lung cancer inflammation index [ALI: body mass index × serum albumin/neutrophil-to-lymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: This retrospective study included 672 stage IV NSCLC patients treated with programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. RESULTS: High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) = 0.402, P < 0.0001, n = 460], but not chemo-immunotherapy (HR = 0.624, P = 0.111, n = 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P = 0.008) and time-on-treatment (HR = 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR = 0.694, P = 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor proportion score ≥50% receiving first-line ICI monotherapy, a high ALI score >18 identified a subset with longer OS and time-on-treatment (median 35 and 16 months, respectively), similar to these under chemo-immunotherapy. CONCLUSIONS: The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-L1 inhibitors alone, but not in combination with chemotherapy. Its association with outcomes appears to be stronger than that of other widely used parameters. For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Inflamação , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos
2.
Breast Cancer Res Treat ; 182(1): 85-96, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32418045

RESUMO

PURPOSE: The efficacy of nab-paclitaxel in patients with metastatic breast cancer (MBC) has been demonstrated in randomized clinical trials. However, real-world evidence on effectiveness remains limited. PATIENTS AND METHODS: The primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC treated with nab-paclitaxel. Secondary objectives included progression-free survival (PFS), overall survival (OS) and quality of life, assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument. RESULTS: Eligible patients (N = 150; 36% with de novo MBC presentation) with a median age of 64.5 years were enrolled (86% were ER+, 33.3% (50/150) were ≥ 70 years of age and 53% were treated in the third or later line of treatment). A median of 6 cycles were administered but 26% of patients required dose reduction due to toxicity. The ORR was 26.7% [95% confidence interval (CI) 19.6-33.7], the median PFS was 6.2 months (95% CI 5.2-7.3), and the median OS 21.1 months (95% CI 17.2-not estimable). There was no statistical significant difference in the median PFS of patients < and ≥ 70 years of age. The patients' baseline FACT-B total score remained unchanged. The serious and non-serious adverse event incidence rates were 13% and 48%, respectively. CONCLUSIONS: This prospective study provides further evidence on quality of life, efficacy, and safety of nab-paclitaxel in patients with MBC and sheds more light in special subpopulations such as the elderly and those treated beyond the second line.


Assuntos
Albuminas/uso terapêutico , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Paclitaxel/uso terapêutico , Qualidade de Vida , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/metabolismo , Carcinoma Lobular/secundário , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida
3.
Support Care Cancer ; 27(12): 4535-4542, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30919155

RESUMO

PURPOSE: Cutaneous toxicities from novel anticancer treatments are an emerging problem in dermato-oncology. However, the prevalence of those toxicities and necessity of skin consultations are currently unknown. The purpose of our study was to perform an epidemiologic analysis of cutaneous toxicities that were referred to our cutaneous toxicity clinic in Athens, Greece. METHODS: All patients examined at the oncodermatology department over a 42-month period were included. Gender, age, type of cancer, type of antineoplastic treatment, and type of toxicity were recorded and analyzed. RESULTS: Four hundred fifty-nine patients (182 males, 277 females) with mean age (SD) 60.6 years (13.05) were included in the analysis. Six hundred seventy-two cutaneous toxicities were recorded. Chemotherapy-induced toxicities were the most commonly recorded incidents, with taxanes being the most commonly involved agent. Immune-related adverse events (IRAEs) have steadily increased over the past 3 years. Treatment modifications due to skin toxicities were more common in patients treated with targeted agents and immune checkpoint inhibitors than in those treated with chemotherapy. The toxicities that led to the most treatment modifications were acneiform eruptions and perionychias. The most common IRAEs recorded were psoriasis in 11 patients, followed by pruritus, macular rash, and lichenoid-type eruptions. In addition, 4 interesting cases of IRAEs are discussed. CONCLUSION: Antineoplastic treatments can lead to a wide range of cutaneous toxicities. Our study underlines the need for a multidisciplinary approach in oncologic patients. The dermatologists' role is crucial in effectively managing those reactions and preventing antineoplastic drug dose adjustments or discontinuation of treatment.


Assuntos
Antineoplásicos/efeitos adversos , Toxidermias/etiologia , Pele/efeitos dos fármacos , Erupções Acneiformes/induzido quimicamente , Idoso , Exantema/induzido quimicamente , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Estudos Retrospectivos
4.
Eur J Cancer Care (Engl) ; 27(4): e12850, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29672984

RESUMO

Cardiopulmonary resuscitation (CPR) in patients with cancer is an ethical issue of worldwide interest. A questionnaire-based study was carried out in a Greek oncology hospital aiming to explore the attitude of Greek cancer patients towards CPR. Overall, 200 patients (94 male, 106 female) of a mean age of 62.8 years took part in the study. Only 42 (21%) patients indicated that they knew what CPR really involves and only 20 (10%) patients thought that CPR has serious side effects, while the mean estimated in-hospital CPR survival rate to hospital discharge was 56.6% (minimum = 2%, maximum = 99%, standard deviation [SD] = 25.16) and 42.1% (minimum = 0%, maximum = 90%, SD = 24.56%) in case of unselected and cancer patients respectively. Despite their poor knowledge, 177 (88.5%) patients were willing to undergo CPR in case of an in-hospital arrest, 127 (63.5%) thought that they had the right to choose their CPR status and 141 (70.5%) believed that they should be asked about it when they enter the hospital. Most patients (36%) wanted their CPR status to be decided by themselves, their family and their doctor jointly. These findings indicate that specific measures should be applied to clinical practice in order to best manage this ethical issue, and consequently, improve cancer care.


Assuntos
Reanimação Cardiopulmonar , Conhecimentos, Atitudes e Prática em Saúde , Parada Cardíaca/terapia , Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
5.
Br J Cancer ; 117(1): 8-14, 2017 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-28510571

RESUMO

BACKGROUND: Pazopanib is a tyrosine kinase inhibitor with antiangiogenic activity. Vascular endothelial growth factor expression is increased in SCLC and is correlated with poor prognosis. The efficacy and tolerance of second-line pazopanib in SCLC was evaluated. PATIENTS AND METHODS: Patients with platinum-sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were enrolled in a multicentre phase II study. The primary end point was the progression-free survival rate (PFS-R) at week 8 in each cohort. Pazopanib (800 mg per day per os) was administered until progressive disease (PD). Circulating tumour cells (CTCs) were enumerated using the Cellsearch assay. RESULTS: All patients were evaluable for response and toxicity. In the intention-to-treat analysis, eight (13.8%) patients achieved partial response (PR) (95% confidence interval (CI): 5.0-22.7), 20 (34.5%) stable disease (SD) and 30 (51.7%) PD. Accrual in cohort B was halted because the hard-stop rule was met; in cohort A, the PFS-R was 59% (95% CI: 43.5-74.4; PR=7, SD=16). Nine (23.1%) patients received pazopanib for >6 months and 3 of them for >12 months. One pazopanib cycle resulted to a significant decrease to the number of patients with ⩾5 CTCs/7.5 ml of blood (20%) compared with baseline (50%). The median PFS and OS for all patients was 2.5 months (95% CI: 1.9-3.1 months) and 6.0 months (95% CI: 3.8-8.2 months), respectively (cohort A: PFS=3.7 months and OS=8.0 months). No unexpected toxicity was observed. CONCLUSIONS: Second-line treatment with pazopanib in platinum-sensitive SCLC is well tolerated and resulted in promising objective responses and disease control; CTC enumeration might serve as a reliable surrogate biomarker of response.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Células Neoplásicas Circulantes , Pirimidinas/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos , Carboplatina , Cisplatino , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Indazóis , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Lung Cancer ; 104: 16-23, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28212995

RESUMO

OBJECTIVES: To investigate the effect of pazopanib on different CTCs subpopulations in patients with recurrent SCLC and evaluate their clinical relevance. METHODS: Peripheral blood was obtained before the administration of pazopanib (n=56 patients), after the first cycle (n=35 patients) and at disease progression (n=45 patients). CTCs were detected by CellSearch and double immunofluorescent staining using antibodies against the cytokeratins (CK), TTF-1, CD56 and VEGFR2. RESULTS: Before treatment, CTCs could be detected in 50% of patients by CellSearch; phenotypic characterization of CTCs demonstrated that 50%, 46.6% and 27.6% of patients had CD45-/TTF1+, CD45-/CD56+ and TTF-1+/CD56+ CTCs, respectively. Additionally, 59% of CTCs were TTF-1+/VEGFR2+ and 53% CK+/VEGFR2+. One pazopanib cycle resulted to a significant decrease of the number of CTCs (CellSearch: p=0.043) and CK+/VEGFR2+ cells (p=0.027). At the time of PD, both the total number of CTCs (p=0.027) and the number of the different subpopulations were significantly increased compared to post-1st cycle values; this increased CTCs number was associated with a significant increase of TTF-1+/VEGFR2+ (p=0.028) and CK+/VEGFR2+ CTCs (p=0.018). In multivariate analysis, only the number of CTCs as assessed by CellSearch after one treatment cycle was significantly associated with OS (HR: 0.21; p=0.005). CONCLUSIONS: Pazopanib has a significant effect on different subpopulations of CTCs in patients with relapsed SCLC; the detection of VEGFR2+ CTCs during treatment could be a surrogate marker associated with resistance to pazopanib.


Assuntos
Inibidores da Angiogênese/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Células Neoplásicas Circulantes/efeitos dos fármacos , Pirimidinas/farmacologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Sulfonamidas/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Biomarcadores Tumorais/metabolismo , Antígeno CD56/imunologia , Proteínas de Ligação a DNA/imunologia , Feminino , Humanos , Indazóis , Antígenos Comuns de Leucócito/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Células Neoplásicas Circulantes/patologia , Ensaios Clínicos Controlados não Aleatórios como Assunto , Pirimidinas/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Sulfonamidas/administração & dosagem , Fatores de Transcrição , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/imunologia
7.
Pharmacogenomics J ; 14(3): 248-55, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24061601

RESUMO

The aim of the study was to evaluate the association of vascular endothelial growth factor (VEGF) genotypes with treatment efficacy in a phase II trial. This study evaluated weekly docetaxel, as first-line treatment for metastatic breast cancer. Existing data from in vitro and animal model experiments suggest that docetaxel at low doses has anti-angiogenic activity. DNA was extracted from blood samples of 86 patients participating in the trial. Genotyping was performed for selected single-nucleotide polymorphisms (SNPs; VEGF-2578, -1498, -1154, and +936). Moreover, due to the highly polymorphic nature of the studied areas, we were able to analyze additional registered SNPs. All candidate genotypes were evaluated for associations with overall survival (OS), progression-free survival (PFS) and response rate. The VEGF-1154 GG genotype was more frequent in patients not responding to treatment compared with responders (42.9% vs 0.0%, P=0.048). Moreover, the VEGF-2578 AA genotype was associated with longer PFS compared with CC (hazard ratio (HR)=0.40; 95% confidence interval (CI) 0.17-0.98; pairwise P=0.0457). Patients with the VEGF-1190 GG genotype demonstrated shorter PFS compared with those with the alternative genotypes (GA and AA) combined (HR=3.85; 95% CI: 1.20-12.50; P=0.0224). In addition, the VEGF-2551/-2534 homozygous del18bp and VEGF-2430/-2425 homozygous ins1bp genotypes were associated with worse PFS compared with no deletion and no insertion, respectively (HR=2.49; 95% CI: 1.02-6.07; pairwise P=0.0442 and HR=2.57; 95% CI: 1.05-6.27; pairwise P=0.0385, respectively). Furthermore, patients with the VEGF-1498 CC genotype exhibited longer median OS compared with those with the alternatives genotypes (CT and TT) combined (HR=0.27; 95% CI: 0.08-0.89; P=0.0311). In multivariate analysis, the VEGF-2578 AA genotype retained its significance (P=0.0220) for PFS. Our results support the association of specific VEGF genotypes with clinical outcome in patients with metastatic breast cancer treated with a potentially anti-angiogenic regimen, such as weekly docetaxel. However, current results should be validated prospectively in larger cohorts.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Polimorfismo Genético , Taxoides/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Sequência de Bases , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Primers do DNA , Docetaxel , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Taxoides/administração & dosagem
8.
Cancer Chemother Pharmacol ; 71(1): 245-55, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23096218

RESUMO

PURPOSE: RACGAP1 is a Rac GTPase-activating protein involved in cell growth regulation, cell transformation and metastasis. The aim of the present study was to explore the prognostic and/or predictive significance of RACGAP1 mRNA expression on disease-free survival (DFS) and overall survival (OS) in high-risk early breast cancer patients and compare it to that of Ki67 protein expression and to the Nottingham prognostic index (NPI). METHODS: A total of 595 high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative dose-dense sequential chemotherapy with epirubicin followed by CMF with or without paclitaxel. RNA was extracted from 314 formalin-fixed paraffin-embedded primary tumor tissue samples followed by one-step quantitative RT-PCR for assessing RACGAP1 mRNA expression. RESULTS: High RACGAP1 mRNA expression (above the median) was associated with poor DFS (log-rank, p = 0.002) and OS (p < 0.001). High histological grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of RACGAP1. Results of the Cox multivariate regression analysis revealed that high RACGAP1 mRNA expression independently predicted poor overall survival (Wald's p = 0.008). High Ki67 protein expression was also an adverse prognostic factor for death (p = 0.016), while high NPI score values were not. CONCLUSIONS: High RACGAP1 mRNA expression, as assessed by qRT-PCR, was found to be of adverse prognostic significance in high-risk early breast cancer patients treated with dose-dense sequential chemotherapy. The utility of RACGAP1 mRNA expression in patient selection for treatment with aggressive chemotherapy regimens should be further explored and validated in larger cohorts.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proteínas Ativadoras de GTPase/genética , Regulação Neoplásica da Expressão Gênica , Antígeno Ki-67/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Seleção de Pacientes , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Adulto Jovem
9.
Ann Oncol ; 24(4): 1011-7, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23136231

RESUMO

BACKGROUND: The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC. PATIENTS AND METHODS: One hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events). RESULTS: The median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%). CONCLUSIONS: Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population. Clinical Trial Number ACTRN12610000845033, www.anzctr.org.au.


Assuntos
Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias da Bexiga Urinária/cirurgia , Urotélio/cirurgia , Vimblastina/administração & dosagem , Gencitabina
10.
Ann Oncol ; 23(2): 427-35, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21525406

RESUMO

BACKGROUND: Concomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial. PATIENTS AND METHODS: Totally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m(2), epirubicin 75 mg/m(2) and paclitaxel (Taxol) 175 mg/m(2) (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m(2) (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients). RESULTS: Sixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT. CONCLUSION: IC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma , Quimiorradioterapia , Cisplatino/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Antígeno Ki-67/biossíntese , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Paclitaxel/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Proteína Supressora de Tumor p53/biossíntese , Adulto Jovem
11.
Ann Oncol ; 22(4): 827-834, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20880999

RESUMO

BACKGROUND: Paclitaxel (Taxol) and vinorelbine have shown synergism of cytotoxic effects in vitro and clinical activity in phase I and II studies. This combination was compared prospectively with the paclitaxel/gemcitabine regimen in non-operable non-small-cell lung cancer. PATIENTS AND METHODS: Chemotherapy-naive patients, stage IIIbwet and IV with performance status (0-1), were randomized to receive paclitaxel 200 mg/m(2) on day 1 plus gemcitabine 1 gm/m(2) (group A) on days 1 and 8 every 3 weeks or paclitaxel 80 mg/m(2) plus vinorelbine 22.5 mg/m(2) (group B) on days 1, 8 and 15 every 4 weeks. RESULTS: A total of 398 out of 415 patients were eligible for analysis on intent-to-treat basis (group A: 196, group B: 202). Progression-free survival (PFS) was 5.0 months [95% confidence interval (CI) 4.3-5.6] and 4.4 months (95% CI 3.7-5.2) for groups A and B respectively (P=0.365). Median survival was 11.1 months (95% CI 9.2-13.0) and 8.6 months (95% CI 7.0-10.2) for groups A and B respectively (P = 0.147). Grade 3/4 neutropenia and leukopenia were worse in group B (P<0.001, in both cases). Febrile neutropenia and severe infections were more prominent (P<0.001, P=0.029 respectively) in group B. CONCLUSION: Although response rate, PFS and survival were non-different in both groups, toxicity was significantly worse in group B and therefore further investigation of P-Vin is of no value.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Vimblastina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Grécia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Vinorelbina , Gencitabina
13.
Cancer Chemother Pharmacol ; 65(6): 1009-21, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20130877

RESUMO

The optimal adjuvant treatment for gastric cancer remains controversial. We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen, in patients with high-risk gastric cancer, with that of the same chemotherapy plus radiation therapy (RT). In addition, we evaluated the prognostic and/or predictive value of a panel of molecular markers. Patients with histologically proven, radically resected gastric cancer, stage > or =T3 and/or N+ were randomized to 6 cycles of docetaxel with cisplatin, both at 75 mg/m2 every 3 weeks (arm A) or the same treatment with RT (arm B; 45 Gy). Due to excessive nausea and vomiting, cisplatin was substituted by carboplatin at AUC (area under the curve) of 5 after the first 45 patients (22 group A, 23 group B). The prognostic value of EGFR, ERCC1, HER2, MET/HGFR, MAP-Tau, and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays (TMAs). A total of 147 patients were randomized. After a median follow-up of 53.7 months, no differences in overall (OS) and disease-free survival (DFS) were found between the two arms. The most common grade 3/4 toxicities for arms A and B (excluding alopecia) were non-febrile neutropenia (11 and 17%, respectively), febrile neutropenia (9 and 7%) and diarrhea (7 and 4%, respectively). Patients with ERCC1 positive tumors had significantly longer median DFS (33.1 vs. 11.8 months, Wald P = 0.016) and OS (63.2 vs. 18.8 months, Wald P = 0.046). Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk, radically resected gastric cancer. However, the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/análise , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Diarreia/induzido quimicamente , Docetaxel , Receptores ErbB/análise , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Prognóstico , Receptor ErbB-2/análise , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Análise Serial de Tecidos , Resultado do Tratamento
14.
J Chemother ; 21(5): 573-83, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19933050

RESUMO

It is controversial whether non-small cell lung cancer (NSCLC) in the elderly constitutes a distinct clinico-biological entity compared to younger counterparts. As reported data are scant and discordant, we sought to analyze retrospectively the medical records of Hellenic NSCLC patients aged >70 years and compare them with those of age (70-45 years) and younger (<45 years) patients. Records were abstracted from the Hellenic Cooperative Oncology Group (HeCOG) cancer registry database. Presentation, management and outcome data of 417 elderly patients aged > or =70, 1374 age 70-45 years old and 115 patients aged < or =45 years old with histologically confirmed NSCLC managed from 1989 until 2004 were retrieved and compared. Elderly patients differed significantly in terms of presence of symptoms (p<0.001), including thoracic pain (p=0.003), dyspnea (p<0.001), cough (p<0.001) and fatigue (p<0.001), eastern Cooperative Oncology Group performance status (PS) 2-3 (p<0.001), and histological type (more commonly diagnosed with squamous cell carcinoma (p<0.002) and less frequently with adenocarcinoma). Although elderly patients had significantly higher rates of PS 2-3, they had significantly better median time to disease progression (TTP) compared to the younger counterpart (6.4 versus 4.3 months p=0.047). Overall survival (OS) was not significantly different between elderly and young patients (median OS 11.8 versus 11.5 months; p=0.6), but platinum-based chemotherapy and radiotherapy were variables associated favorably with TTP and survival in the elderly. This large retrospective series presents strong evidence that NSCLC constitutes a similar clinicopathologic entity in elderly and young individuals with discretely differing biological behavior and that elderly symptomatic patients should be considered for effective anticancer treatment whenever possible.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Grandes/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/terapia , Neoplasias Pulmonares/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Fatores Etários , Idoso , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Quimioterapia Adjuvante , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Sistema de Registros , Taxa de Sobrevida , Resultado do Tratamento
15.
Anticancer Res ; 29(2): 693-702, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19331224

RESUMO

BACKGROUND: Erythropoietin corrects and prevents anemia and decreases the need for red blood cell (RBC) transfusions; its impact on quality of life (QOL) of cancer patients receiving chemotherapy is not clear. PATIENTS AND METHODS: 399 patients with solid tumors and Hb level of < or = 12 g/dl receiving chemotherapy were randomized to receive or not 10,000 IU epoetin-alpha thrice weekly. QOL was measured by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale and various subscales at baseline, at two months and at the end of the study. RESULTS: Changes in the average QOL scores were similar in the two groups. The improvement in Hb levels was significantly higher for the epoetin-alpha group, with a decrease in transfusion requirements compared to the control group. CONCLUSION: Epoetin-alpha does not improve QOL of patients with solid tumors receiving chemotherapy as assessed using FACT-An scale and various subscales, despite improving Hb levels and reducing transfusion requirements.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Eritropoetina/uso terapêutico , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/tratamento farmacológico , Anemia/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transfusão de Sangue , Epoetina alfa , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Qualidade de Vida , Proteínas Recombinantes , Resultado do Tratamento , Adulto Jovem
16.
Anticancer Res ; 29(2): 745-51, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19331231

RESUMO

BACKGROUND: The aim of this retrospective study was to present the epidemiological, pathological and clinical characteristics and treatment results of Greek women with epithelial ovarian cancer (EOC). PATIENTS AND METHODS: From February 1976 to December 2006, 1,791 patients had been diagnosed, treated and followed up in the participating centers of the Hellenic Cooperative Oncology Group (HeCOG). Cox-regression analysis was carried out in order to identify possible prognostic factors. RESULTS: The median age at diagnosis was 60 years. Seventy-five percent had a performance status (PS) of 0-1, 58.5% had a serous carcinoma, 36% had poorly differentiated tumors and 57% had International Federation of Gynecology and Obstetrics (FIGO) stage III disease. Approximately half of the patients had been subjected to a total abdominal hysterectomy, bilateral oophorectomy and omentectomy, and 80% of them had undergone optimal debulking surgery. Among 1,462 patients with advanced disease, 96% had received platinum-based chemotherapy, while platinum plus paclitaxel had been administered to two-thirds of them. Among 609 patients with known data for response, 34% had achieved a complete objective response (CR) and 30% a partial response (PR), resulting in an overall response rate (RR) of 64%. Performance status, FIGO stage and residual disease (RD) after cytoreductive surgery were the strongest prognostic factors for time-to-tumor progression (TTP) and for overall survival (OS), while age was found to be significant only for OS. The median TTP was 107 months (95% confidence interval (CI), 92-121 months) for patients with stages I-II, 17 months (95% CI, 15-18 months) for those with stages III-IV 96 months (95% CI, 58-133 months) for patients without RD and 17 months (95% CI, 15-18 months) for those with RD. Median OS had not been reached for the patients with stages I-II, while it was 40 months (95% CI, 37-43 months) for those with stages III-IV, 141 months (95% CI, 103-179 months) for patients without RD and 42 months (95% CI, 39-45 months) for those with RD. CONCLUSION: There were no significant differences in patient characteristics or types of treatments administered in Greek women with EOC in comparison with those reported in the English literature.


Assuntos
Neoplasias Ovarianas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Grécia/epidemiologia , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
17.
Breast Cancer Res Treat ; 115(1): 87-99, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18483853

RESUMO

BACKGROUND: Effective anthracycline-free combinations need to be evaluated in metastatic breast cancer (MBC), due to the increased number of patients treated with anthracycline-based adjuvant chemotherapy. PATIENTS AND METHODS: Patients with MBC were randomized to paclitaxel and carboplatin (PCb) every 3 weeks or docetaxel and gemcitabine (GDoc) every 3 weeks or weekly paclitaxel (Pw). Trastuzumab was given to patients with HER-2 over-expressing tumors. The primary endpoint of the study was survival. Quality of life (QoL) and cost were assessed. RESULTS: Totally, 416 eligible patients entered the study. Median survival times were 29.9 months for PCb, 26.9 for GDoc and 41.0 for Pw (P = 0.037). According to multivariate analysis, adjuvant chemotherapy, >1 metastatic sites, lack of maintenance hormonal therapy, and worse performance status (PS) were significant adverse prognostic factors for survival, while Pw when compared to GDoc improved survival (P = 0.03), as well as when compared to PCb in the subgroup of patients with PS = 1 (P = 0.01, treatment by PS interaction P = 0.03). No significant differences in terms of time to progression were found. Severe myelotoxicity and mucositis were more frequent with GDoc, while severe neuropathy with PCb and Pw. QoL changes did not differ significantly between treatment groups, while cost analysis favored Pw. CONCLUSIONS: Pw appears to be the most preferable choice among the 3 anthracycline-free taxanes-based regimens tested in the present study.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Taxoides/administração & dosagem , Trastuzumab , Gencitabina
18.
Eur J Cancer ; 44(12): 1693-700, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18639450

RESUMO

The primary objective was to compare the 3-year survival of rectal cancer patients randomised postoperatively to irinotecan (IRI), Leucovorin (LV) and bolus 5-fluorouracil (5FU) or LV-bolus 5FU with radiotherapy. Secondary objectives included disease-free survival, local relapse and toxicity. The study included 321 eligible patients. The treatment consisted of weekly administration of IRI 80 mg/m(2) intravenously (IV), LV 200 mg/m(2) and 5FU 450 mg/m(2) bolus (arm A) versus LV 200 mg/m(2) and 5FU 450 mg/m(2) IV bolus (arm B). One cycle included four infusions and treatment was continued for a total of six cycles. The first cycle was followed by pelvic irradiation plus 5FU. There were no differences between the arms in 3-year overall, disease-free and local relapse-free survival. Grades 3 and 4 toxicity was similar in both the arms with the exception of leucopaenia, neutropaenia and alopecia, which were higher in the IRI arm. IRI added to adjuvant radiochemotherapy with LV and bolus 5FU was not shown to improve survival, whereas the incidence of severe leucopaenia was significantly higher in the IRI arm.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Quimioterapia Adjuvante , Estudos de Coortes , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Análise de Sobrevida , Resultado do Tratamento
19.
Ann Oncol ; 19(1): 115-22, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17938425

RESUMO

BACKGROUND: This phase III study was designed to compare the combination paclitaxel (Taxol)-gemcitabine (PG) versus carboplatin-gemcitabine (CG) in patients with advanced inoperable non-small-cell lung cancer. METHODS: Chemotherapy-naive patients with performance status of zero or one were randomized to gemcitabine 1 gm/m(2) on days 1 and 8 plus either paclitaxel 200 mg/m(2) on day 1 (arm A) or carboplatin at an area under the concentration-time curve of 6 mg on day 1 (arm B) every 3 weeks. Primary end point was overall survival (OS). Secondary end points included objective response (OR), time to progression and toxicity. RESULTS: A total of 512 patients were enrolled and 452 eligible (arm A, 225; arm B, 227) were analyzed. All characteristics were well balanced with the exception of vena cava obstruction symptoms and lymph node involvement. Median survival was 9.97 months [95% confidence interval (CI) 8.74-12.0] for group A and 10.49 (95% CI 9.04-11.94) for group B. There was no difference in the OS, 1-year survival, OR and TtP. However, statistically significant differences were seen in toxicity. CONCLUSION: The two regimens are equally active. Myelotoxicity is worse in the CG group whereas alopecia, myalgia and neurotoxicity worse in the PG group.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cimetidina/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Dexametasona/administração & dosagem , Difenidramina/administração & dosagem , Feminino , Cardiopatias/induzido quimicamente , Doenças Hematológicas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Ondansetron/administração & dosagem , Paclitaxel/administração & dosagem , Pré-Medicação , Modelos de Riscos Proporcionais , Gencitabina
20.
Cancer Chemother Pharmacol ; 62(2): 277-84, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17901952

RESUMO

BACKGROUND: Cancer of unknown primary (CUP) lacks established therapy although it affects 3% of cancer patients. We evaluated the irinotecan-oxaliplatin combination (IROX regimen) in previously untreated patients with non-favorable subsets of unknown primary carcinomas. METHODS: This was a multicenter phase-II trial. Protocol treatment consisted of oxaliplatin 80 mg/m(2) followed by irinotecan 160 mg/m(2) administered every 3 weeks. The primary end points were response rate and toxicity, and secondary end points were time to progression and survival. RESULTS: Forty-seven patients with liver, bone or multiple visceral metastases entered into the trial and received a median 6 chemotherapy cycles (1-11). The regimen was very well tolerated with one febrile neutropenia case and six cases with diarrhea grade 3 (16%). In intent-to-treat analysis the tumor response rate was 13% (95% CI = 4.8-25.7%) and 12 patients (27%, 95%CI 13.9-40.4%) had at least 4 months' duration of disease stabilization. The median time to progression was 2.7 months and the median survival was 9.5 months, with 40% of patients alive at 1 year. CONCLUSIONS: The IROX regimen demonstrated similar efficacy and a favorable toxicity profile compared to other more toxic chemotherapy combinations in patients with poor-prognosis CUP.


Assuntos
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/mortalidade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina
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