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1.
Target Oncol ; 16(6): 789-799, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34755244

RESUMO

BACKGROUND: Real-world data on extended follow-up of patients with BRAF V600-mutant metastatic melanoma are limited. We investigated dabrafenib plus trametinib (dab + tram) outside of a clinical trial setting (Individual Patient Program; DESCRIBE Italy). OBJECTIVE: To describe the baseline features, treatment patterns, efficacy, and safety outcomes in patients with BRAF V600-mutant unresectable or metastatic melanoma who had received dab + tram as part of the Managed Access Program (MAP) in Italy. PATIENTS AND METHODS: An observational, retrospective chart review was conducted in Italian patients with BRAF V600-mutant unresectable stage III/IV melanoma receiving dab + tram as part of the MAP. Baseline features, treatment patterns, efficacy, and safety outcomes were evaluated. RESULTS: Overall, 499 patients were included in this analysis. BRAF V600E mutation was seen in 81.4% of patients. Overall response rate achieved in 243 of the 390 evaluable patients was 62.3% (95% CI 57.5-67.1). Median progression-free survival (PFS) was 9.3 months (95% CI 8.6-10.6). Subgroup analyses revealed that patients with normal lactate dehydrogenase (LDH) and ≤ three metastatic sites without brain metastases at baseline had better outcomes. With normal LDH at baseline, median PFS for patients with one or two metastatic sites other than cerebral was 18 months. No new safety signals were observed. Treatment was permanently discontinued because of treatment-emergent adverse events (TEAEs) in 9.2% of patients, and pyrexia (27.3%) was the most common TEAE, with a lower incidence than that in the phase 3 studies of dab + tram. CONCLUSION: Treatment of BRAF V600E-mutant metastatic melanoma with dab + tram in the real-world setting was effective and safe, including the unselected population with several patients having a high tumor burden - concordant with the results of the pivotal phase 3 studies of dab + tram.


Assuntos
Melanoma , Segunda Neoplasia Primária , Neoplasias Cutâneas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Imidazóis , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Mutação , Segunda Neoplasia Primária/etiologia , Oximas/farmacologia , Oximas/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/farmacologia , Piridonas/uso terapêutico , Pirimidinonas , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico
2.
Eur J Cancer ; 155: 56-63, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34358777

RESUMO

BACKGROUND: Pre-clinical data suggest that docetaxel and enzalutamide interfere with androgen receptor translocation and signalling. The aim of this study is to assess the efficacy of their concurrent administration in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). METHODS: In this open-label, randomised, phase II trial, previously untreated mCRPC patients were randomised 1:1 to receive eight 21-d courses of docetaxel 75 mg/m2, oral prednisone 5 mg twice daily and oral enzalutamide 160 mg/d (arm DE), or the same treatment without enzalutamide (arm D). The primary end-point was the percentage of patients without investigator-assessed disease progression 6 months after the first docetaxel administration. RESULTS: The 246 eligible patients were randomly assigned to receive docetaxel, prednisone and enzalutamide (n = 120) or docetaxel and prednisone (n = 126). The 6-month progression rate was 12.5% (95% confidence interval [CI] 8.1-20.6) in arm DE and 27.8% (95% CI 22.8-39.4) in arm D (chi-squared test 10.01; P = 0.002). The most frequent grade III-IV adverse events were fatigue (12.5% in arm DE versus 5.6% in arm D), febrile neutropenia (9.3% versus 4.0%) and neutropenia (7.6% versus 5.6%). CONCLUSIONS: The combination of enzalutamide and docetaxel appears to be more clinically beneficial than docetaxel alone in previously untreated mCRPC patients, although serious adverse events were more frequent. Our findings suggest that first-line treatment with this combination could lead to an additional clinical benefit when prompt and prolonged disease control is simultaneously required. Clearly, these results should be considered cautiously because of the study's phase II design and the absence of an overall survival benefit. TRIAL REGISTRATION NUMBERS: EudraCT 2014-000175-43 - NCT02453009.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/uso terapêutico , Docetaxel/uso terapêutico , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Prednisona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Docetaxel/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/farmacologia
3.
Cancer Biother Radiopharm ; 36(5): 391-396, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33769088

RESUMO

Background: The retrospective studies that have so far described the outcomes of the sequential use of life-prolonging agents (LPAs) did not include metastatic castration-resistant prostate cancer (mCRPC) patients who received radium-223 (223Ra) as part of their treatment. Consequently, it is not known whether including 223Ra in the therapeutic sequence has an impact on cumulative survival. The aim of this study was to evaluate this impact by comparing the cumulative overall survival (OS) in two series of mCRPC patients sequentially treated with two or three LPAs after first-line docetaxel (DOC), including 223Ra and not. Materials and Methods: The authors retrospectively reviewed the records of mCRPC patients with bone involvement alone who received two or three LPAs (including 223Ra) after first-line DOC. The control group was a contemporary series of mCRPC patients with bone involvement alone treated with sequences of two or three LPAs other than 223Ra after first-line DOC. Results: Median cumulative OS was 40.6 months in the 223Ra group of 78 patients and 36.2 months in the non-223Ra group of 186 patients (p = 0.08). OS outcomes were significantly influenced by the number of treatment lines, and baseline Eastern Cooperative Oncology Group performance status (PS) and prostate-specific antigen levels. Conclusions: To the best of the authors' knowledge, this is the first study designed to evaluate the impact of introducing 223Ra in the treatment sequences for mCRPC patients, and the results show that its use does not negatively affect cumulative OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/terapia , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/terapia , Compostos Radiofarmacêuticos/uso terapêutico , Rádio (Elemento)/uso terapêutico , Acetato de Abiraterona/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Benzamidas/administração & dosagem , Neoplasias Ósseas/secundário , Terapia Combinada , Docetaxel/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Feniltioidantoína/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagem
5.
J Transl Med ; 17(1): 296, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464635

RESUMO

BACKGROUND: This multi-institutional retrospective real life study was conducted in 22 Italian Oncology Centers and evaluated the role of Axitinib in second line treatment in not selected mRCC patients. METHODS: 148 mRCC patients were evaluated. According to Heng score 15.5%, 60.1% and 24.4% of patients were at poor risk, intermediate and favorable risk, respectively. RESULTS: PFS, OS, DCR and ORR were 7.14 months, 15.5 months, 70.6% and 16.6%, respectively. The duration of prior sunitinib treatment correlated with a longer significant mPFS, 8.8 vs 6.3 months, respectively. Axitinib therapy was safe, without grade 4 adverse events. The most frequent toxicities of all grades were: fatigue (50%), hypertension (26%), and hypothyroidism (18%). G3 blood pressure elevation significantly correlated with longer mPFS and mOS compared to G1-G2 or no toxicity. Dose titration (DT) to 7 mg and 10 mg bid was feasible in 24% with no statistically significant differences in mPFS and mOS. The sunitinib-axitinib sequence was safe and effective, the mOS was 41.15 months. At multivariate analysis, gender, DCR to axitinib and to previous sunitinib correlated significantly with PFS; whereas DCR to axitinib, nephrectomy and Heng score independently affected overall survival. CONCLUSIONS: Axitinib was effective and safe in a not selected real life mRCC population. Trial registration INT - Napoli - 11/16 oss. Registered 20 April 2016. http://www.istitutotumori.na.it.


Assuntos
Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Sunitinibe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Axitinibe/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica
6.
Minerva Urol Nefrol ; 71(5): 508-515, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30957475

RESUMO

BACKGROUND: The aim of this study was to prospectively evaluate the safety and oncologic outcomes of multimodal treatment in high risk-locally advanced prostate cancer patients (PCa). METHODS: High-risk-locally advanced prostate cancer patients without distant metastases before radical prostatectomy (RP) were included. Adjuvant high-dose intensity-modulated radiation therapy (IMRT) with concurrent docetaxel and long-term androgen-deprivation therapy (ADT) were started after 3-6 months from RP. ADT was maintained for two years. Acute and late toxicity were evaluated with the Common Terminology Criteria for Adverse Events (v. 3.0). Biochemical and clinical recurrence-free survival were explored by using the Kaplan-Meier method. RESULTS: Overall 42 patients were included. Acute genitourinary toxicity was observed with Grade I, II, and III in four (9.5%), two (4.8%), and one (2.3%) patients, respectively. Acute gastrointestinal toxicity was reported to be of Grade I and II in 12 (29.3%) and three (7.2%) patients, respectively. In these patients, concomitant genito-urinary and gastrointestinal toxicity occurred in three (7.2%) cases. A residual GU Grade I toxicity was present only in one patient. Toxicity due to CHT was found in four (9.5%) patients. Complete continence after RP and IMRT was achieved in 32 patients (76.2%). After a median follow-up of 3.4 years, BCR and clinical recurrence were observed in 16.7% and 9.5% of patients, respectively. A 5-year biochemical and clinical recurrence-free survival rate were 70.7% and 84.0%, respectively. Five-year overall survival was 93.6%. None of the patients died for prostate cancer during follow-up. CONCLUSIONS: This novel multimodal treatment paradigm for high-risk locally advanced prostate cancer has an acceptable level of toxicity and good oncological outcomes observed after a long follow-up.


Assuntos
Quimiorradioterapia Adjuvante/métodos , Excisão de Linfonodo/métodos , Prostatectomia/métodos , Neoplasias da Próstata/terapia , Idoso , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Quimiorradioterapia Adjuvante/efeitos adversos , Terapia Combinada , Docetaxel/efeitos adversos , Docetaxel/uso terapêutico , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Intervalo Livre de Progressão , Neoplasias da Próstata/cirurgia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Análise de Sobrevida , Resultado do Tratamento
7.
BJU Int ; 123(1): 98-105, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29956884

RESUMO

OBJECTIVE: To report the safety and efficacy results of patients enrolled in the Italian Nivolumab Renal Cell Cancer Expanded Access Programme. PATIENTS AND METHODS: Patients with metastatic renal cell cancer (mRCC) previously treated with agents targeting the vascular endothelial growth factor pathway were eligible to receive nivolumab 3 mg/kg once every 2 weeks. Patients included in the analysis had received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. RESULTS: A total of 389 patients were enrolled between July 2015 and April 2016, of whom 18% were aged ≥75 years, 6.7% had non-clear cell RCC, 49.6% had bone and 8.2% brain metastases, and 79% had received ≥2 previous lines of therapy. The most common any-grade treatment-related AEs were fatigue (13%) and rash (9%). Twenty-two patients (5.7%) discontinued treatment because of AEs. There were no treatment-related deaths. The objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% confidence interval 3.7-6.2) and the 12-month overall survival rate was 63%. Similar survival rates were reported among patients with non-clear-cell histology, elderly patients, those with bone and/or brain metastases, and those who had received prior first-line sunitinib or pazopanib, or prior everolimus. CONCLUSION: The safety and efficacy observed were consistent with those reported in the pivotal Checkmate 025 trial. Results in patients with non-clear-cell mRCC who were elderly, pretreated with everolimus, and had bone and/or brain metastases encourage the use of nivolumab in these categories of patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/secundário , Carcinoma de Células Renais/secundário , Everolimo/uso terapêutico , Feminino , Humanos , Indazóis , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Pirimidinas/uso terapêutico , Critérios de Avaliação de Resposta em Tumores Sólidos , Retratamento , Sulfonamidas/uso terapêutico , Sunitinibe/uso terapêutico , Taxa de Sobrevida
8.
Cytokine ; 113: 50-60, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29958796

RESUMO

BACKGROUND: Immune tolerance seems to correlate with disease progression and T regulatory cells (Tregs) and myeloid-derived suppressor cells play a relevant role in immunosuppression. Cyclophosphamide (Cyt) and Fluorouracil (FU) seem to reduce these cell populations. METHODS AND OBJECTIVE: Establishing safety, feasibility, activity and impact on the immune system (neutrophil/lymphocyte [N/L], platelet/L [Plt/L], monocyte [M] and lymphocyte subpopulation (CD3, CD4, CD8, CD16, HLADR/CD3, Tregs, cells count), CD8/Treg and C-reactive protein (CRP). TREATMENT: 1) Cyt 300 mg/sqm ±â€¯FU 500 mg/sqm day (d) 1 and interleukin 2 (IL-2) 18 MUI/sqm intravenous (I.V.) d 4-6, 18-20 or 2) Cyt 300 mg/sqm + FU 500 mg/sqm day d 1, IL-2 4.5 MUI subcutaneous (S.C.) d 3-6, 17-20. The cycle was repeated every four weeks for 2 cycles. Stable or responding patients (pts) continued therapy for 3 cycles. RESULTS: From February 2014 to December 2016, 13/14 pre-treated pts (mean 3 lines) with solid tumors were enrolled. Male/Female: 1/1. The median age and Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 68 years and 1 respectively. Mean 2 cycles of therapy were administered. G3-4 toxicities presented as diarrhea and bleeding anemia in 2 pts and proteinuria and erhytroderma in 1pt, respectively. Regarding the hematological profile, a more reduction in Plt, less decrease of Plt/Ly, and less increase of Treg with I.V. than S.C. IL-2 administration was observed. However a transient decrease of Treg on day 7 of first cycle in the I.V. IL-2 was reported. RESPONSE: PR 3 (23%), SD 3 (23%), PD 7 (54%). The response duration was 2+ and 3 months in 2 HCC and 18+ months in the pancreatic cancer (PC). Pathological CR was reported in one HCC treated with I.V. IL-2. The median progression-free-survival (PFS) and overall survival (OS) were 1 and 7 months. CONCLUSION: Cyt-FU-IL-2 can be considered safe, feasible and moderately active in heavily pre-treated pts. Plt, Plt/Ly, CD8/Treg and a transient Tregs reduction were observed without significative difference on survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Fluoruracila/uso terapêutico , Interleucina-2/administração & dosagem , Neoplasias/tratamento farmacológico , Idoso , Estudos de Viabilidade , Feminino , Humanos , Infusões Intravenosas/métodos , Injeções Subcutâneas/métodos , Masculino , Uso Off-Label , Intervalo Livre de Progressão
9.
PLoS One ; 13(7): e0199642, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29979712

RESUMO

BACKGROUND: Results from phase III clinical trial CheckMate 025 have established nivolumab as the standard of care for treatment of metastatic renal-cell carcinoma (mRCC) after VEGF inhibitor failure; however, elderly patients are under-represented in the registration trial and little is known about the activity of nivolumab in this subgroup. The purpose of the Expanded Access Program was to provide nivolumab to patients with mRCC who had progressed despite treatment with other agents that were considered standard of care. METHODS: Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months or until progression or unacceptable toxicity. The current analysis included all patients from the EAP Italian cohort who had received ≥1 dose of nivolumab. Adverse events (AEs) were monitored using Common Terminology Criteria for Adverse Events v4.0. RESULTS: A total of 389 patients with advanced RCC were enrolled in the Italian cohort of the EAP and treated with nivolumab. Of these patients, 125 (32%) were at least 70 years of age and 70 (18%) were at least 75 years of age. Efficacy with nivolumab in the elderly patients was similar to that observed in the overall EAP population and in the CheckMate 025 trial. Safety was comparable between the elderly patients and the overall EAP population, and was consistent with what previously reported. CONCLUSION: The final results suggest that elderly patients with pretreated metastatic RCC may benefit from therapy with nivolumab.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Itália , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Retratamento , Análise de Sobrevida , Resultado do Tratamento
10.
Future Oncol ; 14(14): 1347-1354, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29774766

RESUMO

AIM: We report the outcomes observed with nivolumab in metastatic renal cell carcinoma patients with poor prognostic features enrolled in the Italian expanded access program. PATIENTS & METHODS: Nivolumab was available for patients who relapsed after at least one prior systemic treatment in the advanced or metastatic setting. RESULTS: Of 389 patients, 32 (8%) had brain metastasis, 129 (33%) had liver and 193 (50%) had bone metastasis. These subpopulations achieved a disease control rate of 53, 45 and 47%, respectively. Fifty-one patients had G4 tumor, and they showed 23% objective response rate. The safety profile of the subgroups was in line with the expanded access program population. No new safety signals were reported. CONCLUSION: Patients with poor prognostic features may derive relevant benefits from nivolumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Itália , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Nivolumabe , Seleção de Pacientes , Prognóstico , Estudos Prospectivos , Resultado do Tratamento
11.
Int J Mol Sci ; 19(1)2017 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-29295527

RESUMO

The CDH1 gene, coding for the E-cadherin protein, is linked to gastric cancer (GC) susceptibility and tumor invasion. The human epidermal growth factor receptor 2 (HER2) is amplified and overexpressed in a portion of GC. HER2 is an established therapeutic target in metastatic GC (mGC). Trastuzumab, in combination with various chemotherapeutic agents, is a standard treatment for these tumors leading to outcome improvement. Unfortunately, the survival benefit is limited to a fraction of patients. The aim of this study was to improve knowledge of the HER2 and the E-cadherin alterations in the context of GC to characterize subtypes of patients that could better benefit from targeted therapy. An association between the P7-CDH1 haplotype, including two polymorphisms (rs16260A-rs1801552T) and a subset of HER2-positive mGC with better prognosis was observed. Results indicated the potential evaluation of CDH1 haplotypes in mGC to stratify patients that will benefit from trastuzumab-based treatments. Moreover, data may have implications to understanding the HER2 and the E-cadherin interactions in vivo and in response to treatments.


Assuntos
Caderinas/genética , Haplótipos/genética , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto , Idoso , Antígenos CD , Sequência de Bases , Feminino , Frequência do Gene/genética , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Modelos de Riscos Proporcionais , Análise de Sobrevida
12.
Gynecol Oncol ; 144(2): 256-259, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27993479

RESUMO

BACKGROUND: Few data are available on the outcome of surgery after a bevacizumab-containing regimen. The MITO 16A- MaNGO OV2A phase 4 trial evaluates the outcomes of first-line CPB in a clinical-practice-like setting. Here we present the results of the subgroup of patients undergoing IDS after neoadjuvant treatment or suboptimal primary surgery. METHODS: 400 chemonaïve epithelial ovarian cancer patients, age≥18, ECOG PS 0-2 were eligible to receive C (AUC 5 d1, q21) plus P (175mg/m2 d1, q21) and B (15mg/kg d1 q21) for 6cycles followed by B maintenance until cycle 22nd. RESULTS: 79 patients (20%) underwent IDS. Overall, 74 patients received at least one administration of B before IDS. Median age was 61.2, 70% of the patients had FIGO IIIC disease. The median number of cycles before IDS was 3 both for chemotherapy and bevacizumab respectively. A residual disease ≤1cm was achieved in 64 patients (86.5%). Four percent of the patients experienced fever and 4% required blood transfusion after surgery. Surgical wound infection and/or dehiscence, pelvic abscess, intestinal sub-occlusion and fistula were experienced by one patient each. CONCLUSIONS: In the MITO16A-MaNGO OV2A phase 4 trial, combined chemotherapy and bevacizumab did not hamper IDS and the rate of perioperative complications was similar to what expected without bevacizumab. These data support the hypothesis that adding bevacizumab to first line chemotherapy for ovarian cancer might not be denied to patients for whom IDS is planned.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Idoso , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário , Terapia Combinada , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem
13.
Cancer Med ; 5(11): 3272-3281, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27748041

RESUMO

Cetuximab improves efficacy when added to chemotherapy for metastatic colorectal cancer (mCRC). Effective management of skin reactions from cetuximab improves quality of life (QoL), and treatment compliance in clinical trials. No data are available from real-world settings. The ObservEr observational, multicenter, prospective study evaluated QoL, the incidence of skin reactions, and management of chemotherapy plus cetuximab in first-line for mCRC. The primary endpoint was QoL measured with the Dermatology Life Quality Index (DLQI) and EORTC QLQ-C30. Secondary endpoints were the incidence of skin and serious adverse events, median overall and progression-free survival, tumor response, and resection rates. Between May 2011 and November 2012, 228 patients with KRASwt mCRC were enrolled at 28 Italian centers, 225 evaluable, median age 65 years. QoL did not change during treatment and was not affected by the choice of prophylactic or reactive skin management. The incidence of cetuximab-specific grade ≥3 skin reactions was 14%, with no grade 4/5 events. Skin reactions correlated with survival (P = 0.016), and their incidence was influenced by chemotherapy regimen (oxaliplatin vs. irinotecan-Incidence rate ratio [IRR] 1.72, P < 0.0001) and gender (male vs. female-IRR 1.38, P = 0.0008). Compliance at first postbaseline evaluation was 97.75%. Median overall survival was 23.6 months, median progression-free survival 8.3 months. Cetuximab plus chemotherapy did not compromise QoL in the routine clinical setting when patients receive close monitoring plus prophylactic or reactive management of skin reactions. We observed the same correlation between overall survival (OS) and skin reactions reported in controlled clinical trials, also in this setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Qualidade de Vida , Proteínas ras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab/administração & dosagem , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento
15.
Future Oncol ; 12(4): 493-502, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26776493

RESUMO

AIM: To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer. PATIENTS & METHODS: The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes. RESULTS: We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3-4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival. CONCLUSION: The findings of this study suggest that toxicity is acceptable, survival is independent of patient's age and survival can be significantly prolonged by the use of new agents.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel , Humanos , Masculino , Modelos de Riscos Proporcionais , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Retratamento , Estudos Retrospectivos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento
16.
Clin Genitourin Cancer ; 14(2): e161-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26775721

RESUMO

BACKGROUND: The administration of carboplatin AUC 7 has become a standard adjuvant option for patients undergoing orchiectomy for stage I seminoma, in alternative to radiotherapy on retroperitoneal lymphnodes or surveillance. The toxicity of AUC 7 carboplatin appeared manageable in the pivotal trial of Oliver et al, but dose ranges were not reported. Fear of toxicity may induce arbitrary dose reductions, which may potentially compromise patients' outcome. PATIENTS AND METHODS: We reviewed adjuvant carboplatin administration in 115 stage I seminoma patients followed in 11 Italian medical oncology centers since 2005. Clinical and pathological data, modality of carboplatin dose calculation, dose reductions, toxicities, and relapses were recorded. RESULTS: Median age was 35 years (range, 18-65 years), adverse prognostic factors were either T ≥ 4 cm (17.4%) or rete testis invasion (28.7%), both of them (35.7%), none or unspecified (18.3%). GFR was estimated mainly by Cockroft-Gault formula (55.7%) or Jeliffe formula (26.1%), with a median of 105 mL/min (range, 75-209 mL/min). The median dose of carboplatin was 900 mg (range, 690-1535 mg). A dose reduction > 10% was applied to 14 patients. Toxicities were mild fatigue, moderate nausea/vomiting, 5.2% of grade 3 to 4 thrombocytopenia. After a median follow-up of 22.1 months, 5.2% of patients have relapsed in the retroperitoneal lymph nodes. None of the patients that relapsed were treated with reduced dose. All but one achieved complete remission with salvage chemotherapy. CONCLUSIONS: Adjuvant AUC 7 carboplatin reduce relapses of stage I seminoma patients to 5.2%, with manageable toxicities. Dose reductions should be proscribed.


Assuntos
Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Seminoma/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Quimioterapia Adjuvante , Relação Dose-Resposta a Droga , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Seminoma/patologia , Neoplasias Testiculares/patologia , Resultado do Tratamento , Adulto Jovem
17.
Clin Genitourin Cancer ; 14(1): 48-55, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26382222

RESUMO

UNLABELLED: Metastatic castration-resistant prostate cancer mainly affects older men, opening issues about the efficacy and safety of therapies in this population. We have demonstrated that abiraterone, a selective androgen biosynthesis inhibitor, is a safe and active therapeutic option in a subgroup of 47 very elderly adults (aged > 80 years) enrolled in the Italian named patient program, with a tolerability profile and clinical outcomes comparable to those of younger population. BACKGROUND: Prostate cancer mainly affects elderly men, who are often frail and whose reduced physiological reserves and multiple comorbidities increase the risk of side effects. The availability of new drugs has improved the overall survival (OS) of patients with castration-resistant prostate cancer (CRPC) but has increased the number of very elderly CRPC patients receiving anticancer drugs, raising questions about their efficacy and safety in this population. PATIENTS AND METHODS: We assessed the tolerability of abiraterone (AA) in a cohort of very elderly adults with metastatic CRPC (mCRPC) enrolled in the Italian AA named patient program and analyzed their clinical outcomes. We retrospectively reviewed the clinical records of 47 mCRPC patients aged > 80 years who had received AA after docetaxel. The Kaplan-Meier method was used to calculate OS and progression-free survival (PFS). Safety and clinical outcomes were also analyzed by age group (< 80 and > 80 years). Cox regression analysis was used to calculate the differences in PFS and OS between the groups according to the stratification variables. RESULTS: In very elderly men, the prostate-specific antigen response rate was 48.9%, and the median PFS and OS were 8 and 18 months, respectively. The differences in toxicities between the older and younger age groups were not major. The limitation of the present study was mainly its retrospective nature. CONCLUSION: Our data show that AA is active and safe in very elderly patients and leads to outcomes similar to those observed in younger patients, thus confirming that AA is a manageable therapeutic option for this patient population.


Assuntos
Acetato de Abiraterona/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Ensaios de Uso Compassivo , Intervalo Livre de Doença , Docetaxel , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Neoplasias de Próstata Resistentes à Castração/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
18.
Future Oncol ; 11(21): 2881-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26436290

RESUMO

BACKGROUND: The objective of this study was to analyze the impact of visceral metastases in castration-resistant prostate cancer (CRPC) treated with abiraterone. MATERIALS & METHODS: All CRPC patients received abiraterone 1000 mg daily plus prednisone 10 mg orally daily. Liver and lung metastases were considered as visceral metastases. RESULTS: Of 265 CRPC patients, 49 had visceral metastases. Results on progression-free survival were not significantly different in patients with or without visceral metastases. Conversely, the median overall survival between the two groups was 12.4 and 18.5 months (p = 0.01), respectively, and median overall survival of patients with liver-only disease versus other sites was 10.5 versus 18.5 months (p = 0.006), respectively. CONCLUSION: Visceral disease appears to be an important predictor of clinical outcome in CRPC patients treated with abiraterone.


Assuntos
Androstenos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Vísceras/patologia , Idoso , Idoso de 80 Anos ou mais , Androstenos/farmacologia , Antineoplásicos Hormonais/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento
19.
Int J Cancer ; 137(12): 2971-80, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26099996

RESUMO

Pre-therapeutic DPYD pharmacogenetic test to prevent fluoropyrimidines (FL)-related toxicities is not yet common practice in medical oncology. We aimed at investigating the clinical validity of DPYD genetic analysis in a large series of oncological patients. Six hundred three cancer patients, treated with FL, have been retrospectively tested for eight DPYD polymorphisms (DPYD-rs3918290, DPYD-rs55886062, DPYD-rs67376798, DPYD-rs2297595, DPYD-rs1801160, DPYD-rs1801158, DPYD-rs1801159, DPYD-rs17376848) for association with Grade ≥3 toxicity, developed within the first three cycles of therapy. DPYD-rs3918290 and DPYD-rs67376798 were associated to Grade ≥3 toxicity after bootstrap validation and Bonferroni correction (p = 0.003, p = 0.048). DPYD-rs55886062 was not significant likely due to its low allelic frequency, nonetheless one out of two heterozygous patients (compound heterozygous with DPYD-rs3918290) died from toxicity after one cycle. Test specificity for the analysis of DPYD-rs3918290, DPYD-rs55886062 and DPYD-rs67376798 was assessed to 99%. Among the seven patients carrying one variant DPYD-rs3918290, DPYD-rs55886062 or DPYD-rs67376798 allele, not developing Grade ≥3 toxicity, 57% needed a FL dose or schedule modification for moderate chronic toxicity. No other DPYD polymorphism was associated with Grade ≥3 toxicity. Our data demonstrate the clinical validity and specificity of the DPYD-rs3918290, DPYD-rs55886062, DPYD-rs67376798 genotyping test to prevent FL-related Grade ≥3 toxicity and to preserve treatment compliance, and support its introduction in the clinical practice.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Di-Hidrouracila Desidrogenase (NADP)/genética , Fluoruracila/efeitos adversos , Neoplasias/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
20.
Anticancer Res ; 35(6): 3563-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26026126

RESUMO

The lung is a common site of metastases, whose prevalence varies as a function of the primary tumor site, which is usually colorectal cancer (CRC), breast carcinoma, or genitourinary cancers, such as ovary, urinary bladder and renal cell carcinomas. The aim of the present study was to analyze whether the site of primitive tumor affects overall survival (OS) of patients with lung metastases (LMs) who underwent pulmonary metastasectomy. The data of 41 patients with surgically treated CRC (Group A=22 patients) and non-colorectal carcinomas (Group B=19 patients), who developed matachronous LMs and underwent pulmonary metastasectomy with curative intent, were analyzed. The origin of non-colorectal LMs was genitourinary cancer in nine and breast cancer in 10 patients. Overall, there were 22 men and 19 women, with a median age of 65 years (range=31-80); 18 patients had a solitary metastatic tumor, while 23 had two or more LMs. Twenty-nine patients underwent wedge resection, through thoracotomy or video-assisted thoracic surgery, while 12 underwent pulmonary lobectomy. Seventy-five LMs were resected with a 5-tear OS of 48.8%. No difference was found between elderly (≥65 year-old) and younger patients (p=0.26), and between those with solitary or multiple LMs (p=0.62) in terms of survival rate. The female patients had a worse OS (31.6% vs. 63.6%; odds ratio (OR)=3.79, 95% confidence interval (CI)=1.03-13.91, p=0.003) compared to males, independent of the origin of primary cancer. There was no difference in the cumulative survival rates (OR=1.65, 95%CI=0.48-5.69, p=0.42) between Groups and the log-rank test (p=0.75) was not significant. In conclusion, the main pathological characteristics of metastatic lesions and advanced age do not appear to be associated with a poor prognosis in patients with LMs, while the female gender is a negative prognostic factor. Thus, the primary tumor site should not be considered a major criterion in selecting patients for pulmonary metastasectomy.


Assuntos
Neoplasias Colorretais/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Metastasectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Fatores de Risco , Cirurgia Torácica Vídeoassistida , Resultado do Tratamento
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