RESUMO
Head and neck cancers are the fifth among the most common cancers in France. Two thirds of cases occur at an advanced stage. For advanced disease, progression-free survival, despite undeniable progress, remains below 50% at three years. The last 20 years have been marked by the necessity to identify situations where less intense surgery and/or radiotherapy and/or chemotherapy is possible without jeopardizing the prognosis, and situations where a therapeutic intensification is necessary and results in a gain in survival while better preserving function with less toxicity. French cooperative groups gathering radiation oncologists (GORTEC), surgeons (GETTEC) and medical oncologists or physicians involved in the management of systemic treatments in head and neck cancers (GERCOR) are now belonging to the INCa-labelled Intergroup ORL to deal with the challenges of head and neck cancers.
Assuntos
Otolaringologia/organização & administração , Neoplasias Otorrinolaringológicas/terapia , Radioterapia (Especialidade)/organização & administração , Quimiorradioterapia/métodos , Quimiorradioterapia/tendências , Intervalo Livre de Doença , França , Humanos , Quimioterapia de Indução/métodos , Lasers de Gás/uso terapêutico , Oncologia/organização & administração , Tratamentos com Preservação do Órgão/métodos , Otolaringologia/métodos , Otolaringologia/tendências , Neoplasias Otorrinolaringológicas/mortalidade , Neoplasias Otorrinolaringológicas/patologia , Neoplasias Otorrinolaringológicas/virologia , Infecções por Papillomavirus/complicações , Neoplasias dos Seios Paranasais/cirurgia , Fototerapia/métodos , Radioterapia (Especialidade)/métodos , Radioterapia (Especialidade)/tendências , Retratamento/métodos , Robótica/métodos , Biópsia de Linfonodo SentinelaRESUMO
BACKGROUND: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. METHODS: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to-event data. RESULTS: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. CONCLUSIONS: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Quimioterapia Adjuvante/métodos , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/radioterapia , Laringectomia , Radioterapia Adjuvante/métodos , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/fisiopatologia , Carcinoma de Células Escamosas/cirurgia , Quimioterapia Adjuvante/efeitos adversos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Europa (Continente) , Feminino , Fibrose/etiologia , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Edema Laríngeo/etiologia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/fisiopatologia , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Masculino , Pessoa de Meia-Idade , Mucosite/etiologia , Estadiamento de Neoplasias , Seleção de Pacientes , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Recuperação de Função Fisiológica , Indução de Remissão , Projetos de Pesquisa , Terapia de Salvação/métodos , Falha de Tratamento , Resultado do TratamentoRESUMO
The study of epidemiology and of the carcinogenesis in epidermoid carcinomas of the upper aerodigestive tract shows that their occurrence is not random. Tobacco abuse plays a major role, especially because of benzopyrene, mutagen of the P53 gene, however it is associated with many other potentiating factors: alcohol, metals, hydrocarbures, virus, food, climate, genetic fragility that create genetic lesions at the origin of carcinogenesis. The latter occurs as "field cancerization" with multiple alterations of the mucosa and general attack of the control systems of the differentiation, growth and cell apoptosis which usually protect the cell against the phenomena of carcinogenesis. The P53 protein gene, retinoid receptors as well as the system of detoxifying glutathion S transferase are modified at the very early stage of these diseases, these abnormalities can be logically related to epidemiological data. These data lead us therefore to imagine complementary specific reverting therapies of induced genetic abnormalities, through the reexpression of non mutated gene encoding P53 protein and the use of retinoid. These various modalities are reported hereafter.