Câncer de Cólon 2 - Resenha / Colon Cancer 2 - Review

ABSTRACT

Purpose: To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Patients and methods: Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m(2)/d) either alone (arm A, n=379) or combined with oxaliplatin (60 mg/m(2) weekly × 6; arm B, n=368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. Results Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% vs 8% of treated patients; P<.001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ³ 45 Gy (P<.001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% vs 18%, arm A vs arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P=.904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A vs arm B; P=.447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P=.701), and 7% versus 4% had positive circumferential resection margins (P=.239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A vs arm B; P=.014). Conclusion: Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.

RESUMO

Radioterapia em combinação com as fluoropirimidinas é a abordagem neoadjuvante padrão do adenocarcinoma do reto médio e baixo. Na busca de tratamentos cada vez mais eficazes os autores avaliam, uma vez mais, se a adição de oxaliplatina ao tratamento convencional (radioterapia + 5-FU) poderia trazer algum benefício adicional. O estudo foi bem controlado e os pacientes, quase 750 no total, distribuídos aleatoriamente entre os dois braços.A taxa de resposta completa (16%) foi idêntica nos dois grupos. Em ambos os grupos a quase totalidade dos pacientes pode ser submetida à cirurgia, sendo que a necessidade de amputação abdominoperineal foi muito semelhante entre eles (20% versus 18% - p < 0,001).A maior diferença entre os dois braços foi no tocante à toxicidade. Efeitos colaterais graus 3 e 4 foram muito mais frequentes no grupo com oxaliplatina (24% versus 8%).Em suma, o tratamento primário padrão do adenocarcinoma do reto continua sendo a combinação de radioterapia e fluoropirimidina. A inclusão de oxaliplatina não se acompanhou de melhores resultados, o que já fora observado em estudos anteriores.