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5.
Target Oncol ; 13(3): 309-331, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29569164

RESUMO

Metastatic renal cell carcinoma (mRCC) is an incurable malignancy, characterized by its resistance to traditional chemotherapy, radiation, and hormonal therapy. Treatment perspectives and prognosis of patients with mRCC have been significantly improved by advances in the understanding of its molecular pathogenesis, which have led to the development of targeted therapeutics. Different molecular factors derived from the tumor or the host detected in both tissue or serum could be predictive of therapeutic benefit. Some of them suggest a rational selection of patients to be treated with certain therapies, though none have been validated for routine use. This article provides an overview of both clinical and molecular factors associated with predictive or prognostic value in mRCC and emphasizes that both should be considered in parallel to provide the most appropriate, individualized treatment and achieve the best outcomes in clinical practice.


Assuntos
Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Prognóstico
6.
Oncology ; 95(1): 8-12, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29587278

RESUMO

OBJECTIVE: The aim of this study was to assess a risk-adapted strategy for stage I seminoma guided by the presence of rete testis invasion. METHODS: Between January 2013 and December 2015, a total of 135 consecutive patients with stage I seminoma from 18 Spanish tertiary hospitals were included in a prospective multicenter study. Median patient age was 38 years (range 22-60). Preoperative beta-human chorionic gonadotropin was elevated in 9.6% of patients. Rete testis invasion was present in 47.4% of patients. After orchiectomy, subjects with rete testis invasion were treated with 2 courses of adjuvant carboplatin (area under the curve of 7, with 21-day interval). Those without this risk factor were managed by surveillance. Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method. RESULTS: After a median follow-up time of 33 months, only 6 relapses were recorded (5 on surveillance, 1 after carboplatin). These cases were rescued with BEP or EP chemotherapy, and all 135 patients are currently disease free without sequelae. Three-year DFS was 92.0 and 98.2% for patients on surveillance and after carboplatin, respectively. Three-year OS was 100%. CONCLUSION: A risk-adapted approach based on rete testis invasion as a single risk factor is feasible and yielded an excellent outcome with a 3-year DFS of 94.9%.


Assuntos
Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Rede do Testículo/patologia , Seminoma/tratamento farmacológico , Seminoma/patologia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Adulto , Gonadotropina Coriônica/sangue , Terapia Combinada , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Orquiectomia , Estudos Prospectivos , Seminoma/cirurgia , Espanha , Neoplasias Testiculares/cirurgia , Adulto Jovem
7.
J Clin Oncol ; 29(35): 4677-81, 2011 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-22042940

RESUMO

PURPOSE: To confirm the efficacy of a risk-adapted treatment approach for patients with clinical stage I seminoma. The aim was to reduce both the risk of relapse and the proportion of patients receiving adjuvant chemotherapy while maintaining a high cure rate. PATIENTS AND METHODS: From 2004 to 2008, 227 patients were included after orchiectomy in a multicenter study. Eighty-four patients (37%) presented no local risk factors, 44 patients (19%) had tumors larger than 4 cm, 25 patients (11%) had rete testis involvement, and 74 patients (33%) had both criteria. Only the latter group received two courses of adjuvant carboplatin, whereas the rest were managed by surveillance. RESULTS: After a median follow-up time of 34 months, 16 relapses (7%) have been documented (15 [9.8%] among patients on surveillance and one [1.4%] among those treated with carboplatin). All relapses occurred in retroperitoneal lymph nodes, except for one case in pelvic nodes. Median node size was 25 mm, and median time to recurrence was 14 months. All patients were rendered disease-free with chemotherapy. The actuarial 3-year disease-free survival rate was 88.1% (95% CI, 82.3% to 93.9%) for patients on surveillance and 98.0% (95% CI, 94.0% to 100%) for those treated with adjuvant chemotherapy. Overall 3-year survival was 100%. CONCLUSION: With the limitations of the short follow-up duration, we confirm that a risk-adapted approach is effective for stage I seminoma. Adjuvant carboplatin seems adequate treatment for patients with 2 risk criteria, as is active surveillance for those with 0 to one risk factors. More reliable predictive factors are needed to improve the applicability of this model.


Assuntos
Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Seminoma/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Quimioterapia Adjuvante , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Orquiectomia , Estudos Prospectivos , Fatores de Risco , Seminoma/patologia , Seminoma/cirurgia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Adulto Jovem
8.
Lung Cancer ; 62(1): 62-71, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18440089

RESUMO

Concurrent chemoradiotherapy (CCR) followed or preceded by full-dose chemotherapy seems to be a standard treatment for unresectable non-small cell lung cancer (NSCLC). Gemcitabine is a strong radiosensitizer, and a phase I study confirmed the feasibility of CCR with low-dose gemcitabine administered twice-weekly in NSCLC patients. Consequently, we designed a prospective, multicentric, phase II trial to evaluate the efficacy and toxicity of this approach, following induction chemotherapy with cisplatin and gemcitabine. We included patients with unresectable stage III NSCLC, no pleural effusion, adequate pulmonary, renal, liver and hematological functions, Karnofsky index >70 and planned treated volume (PTV) <2200cm3. Treatment consisted of 3 cycles of cisplatin (100mg/m2, d1) and gemcitabine (1250mg/m2, d1 and 8) q3w, followed by CCR (gemcitabine 50mg/m2 on Mondays and Thursdays and radiotherapy 68.4Gy, 1.8Gyqd). After the inclusion of 22 patients (group A), an unacceptable toxicity was detected. Thus, cisplatin dose was reduced to 70mg/m2, and gemcitabine dose was adjusted to 35mg/m2 during CCR. Another 34 patients (33 eligible, group B) were included. Five patients in group A and 6 patients in group B discontinued the study treatment during induction. Thus, 17 and 27 patients, respectively initiated CCR. Hematological toxicity (grades III and IV) was particularly relevant in group A during this phase, with 35 and 23% of thrombopenia and neutropenia, respectively. Nonhematological grades III-IV toxicity of chemoradiation was significant and similar in groups A and B: esophagitis 35.2 and 33.3% and pneumonitis 23.5 and 25.9%, respectively. 40.9% of patients in group A vs. 57.5% in group B completed treatment. Overall response (intention-to-treat analysis) was 68.1% in group A and 63.5% in group B. Median survival was 17.7 months for the whole group with a mean follow-up of 41.2 months. 20% of patients were alive at 3 years. Long-term results of this schedule are encouraging. However, nonhematological toxicity of chemoradiation is substantial and different strategies should be tested to minimize it.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Radioterapia , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Gencitabina
9.
J Clin Oncol ; 23(34): 8717-23, 2005 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-16260698

RESUMO

PURPOSE: To assess the efficacy of a risk-adapted treatment policy for patients with stage I seminoma by using universally accepted risk criteria. PATIENTS AND METHODS: Between 1999 and 2003, 314 patients with clinical stage I seminoma after orchiectomy were prospectively included. One hundred patients (31.8%) presented no risk factors and were managed with surveillance. In contrast, 131 patients (41.7%) had tumors larger than 4 cm, 33 patients (10.5%) had rete testis involvement, and 50 patients (15.9%) had both risk factors. All the latter received two courses of adjuvant carboplatin. RESULTS: Chemotherapy was well tolerated, as only 17 patients (7.9%) presented grade 3 to 4 toxicity. Relapses were observed in six patients (6.0%) on surveillance and in seven patients (3.3%) treated with carboplatin (0.8% of tumors larger than 4 cm, 9.1% of those involving the rete testis, and 6.0% of patients with both risk criteria). All were located at the retroperitoneum, except for one at the spermatic cord. Median tumor size was 25 mm (range, 11 to 70 mm), and median time to relapse was 9 months (range, 4 to 28 months). All patients were rendered disease-free with chemotherapy (etoposide plus cisplatin). Median follow-up was 34 months (range, 12 to 72 months). The actuarial 5-year disease-free survival rate was 93.4% for patients on surveillance and 96.2% for patients treated with adjuvant chemotherapy. Overall 5-year survival was 100%. CONCLUSION: Adjuvant carboplatin is effective in reducing the relapse rate in patients with stage I seminoma and risk factors. A risk-adapted strategy is safe and feasible and should be considered an alternative to systematic approaches, such as irradiation, chemotherapy, or surveillance.


Assuntos
Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Seminoma/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Quimioterapia Adjuvante , Gonadotropina Coriônica Humana Subunidade beta/sangue , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Orquiectomia , Estudos Prospectivos , Fatores de Risco , Seminoma/patologia , Seminoma/cirurgia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Resultado do Tratamento , Vômito/induzido quimicamente
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