Background Patients with refractory colorectal (CRC) cancer have few treatment options. This trial tests the combination of metformin and irinotecan in this setting. Methods A phase 2 single-arm trial was conducted, patients received metformin 2500 mg orally a day plus irinotecan 125 mg/m2 intravenously weekly D1 and D8 every 21 days. The primary endpoint was the disease control rate according to the Response Evaluation Criteria in Solid Tumors version 1.1 at 12 weeks. Results Between December 2015 and January 2018, 41 patients were enrolled. Seventeen patients (41%) met the primary endpoint of disease control in 12 weeks; hence, the study was deemed positive. The median progression-free survival was 3.3 months (CI 95%, 2.0–4.5 months), and the median overall survival was 8.4 months (CI 95%, 5.9–10.8 months). Both mutation RAS status and disease control at 12 weeks impacted overall survival in the multivariate model (HR 2.28, CI 95%, 1.12–4.7, p = 0.02; and HR 0.21, CI 95%, 0.08–0.5, p = 0.001, respectively). The most common adverse event was diarrhoea (29.2% grade 3). Conclusions In this trial, metformin plus irinotecan demonstrated disease control in patients with refractory CRC. Further trials with optimised diarrhoea control are needed to confirm these results.

Resumo O uso de placebo em pesquisa clínica tem sido motivo de debate nos últimos anos, sobretudo após a Associação Médica Mundial publicar, em 2002, nota de esclarecimento do parágrafo 29 da Declaração de Helsinki. O Brasil tem se destacado por sua posição firme e contrária ao uso flexível de placebo. Tanto o Conselho Federal de Medicina quanto o Conselho Nacional de Saúde editaram resoluções que normatizam seu uso no Brasil, de forma a não admiti-lo em caso da existência de um método terapêutico melhor. O presente artigo reforça essa posição e tem por objetivo descrever as diversas aplicações de placebo em pesquisa clínica, bem como trazer à luz a complexa decisão sobre a eticidade de seu uso. Além disso, os autores propõem uma reflexão acerca da utilização de placebo no âmbito da pesquisa, por meio de algoritmos decisórios baseados nas normativas éticas brasileiras.

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e17568 Background: Liver metastasis (mets) from breast cancer is typically associated with poor prognosis. GC is a good option, since patients (pts) have often failed anthracycline and taxane therapy and liver dysfunction may preclude these regimens. Methods: Retrospective study designed to evaluate the clinical outcomes and predictive factors in pts with metastatic breast cancer treated with GC, with special interest for liver mets. Results: From 2004 to 2007, 56 pts were treated with GC. Median age was 52.1 years, 33 pts had PS 0–1, 26 were hormone receptor (HR) negative, 32 had been treated with 3 or more chemotherapy (CT) regimens and 34 had liver mets. The median overall survival (OS) was 7,1 mo (95% CI; 4.3–9.7), the progression free survival was 3.3 mo (95% CI; 2.2–5.5) and the clinical response rate was 25%. OS was 4.0 mo (95% CI; 2.3–8.9) for pts with liver mets and 9.7 mo (95% CI; 6.9–12.9) for pts without liver mets (p = 0.03). No factor showed correlation with OS in pts with liver mets, including age < 45 years (median OS [95% CI]: 2.8 mo [1.8–11.5] versus 4.5 mo [2.5–8.9]; p = 0.74), PS 0–1 (median OS [95% CI]: 7.3 mo [2.5–11.5] versus 2.8 mo [0.8–9.7]; p = 0.55), HR positivity (median OS [95% CI]: 7.3 mo [2.0–11.5] versus 5.9 mo [1.9–9.7]; p = 0.87), bilirubin level ≥ 5 times the superior limit of the normality (median OS [95% CI]: 5.9 mo [0.5–16.7] versus 4.5 mo [2.5–9.7]; p = 0.45), progression free interval after the previous CT ≤ 1 mo (median OS [95% CI]: 4.0 mo [2.0–9.7] versus 7.1 mo [2.5–14.7]; p = 0.93) and previous treatment with ≥ 3 CT regimens (median OS [95% CI]: 7.3 mo [1.0–11.0] versus 4.0 mo [2.0–9.7]; p = 0.93). Conclusions: These data is in accordance with the literature concerning the dismal prognosis in liver mets from breast cancer and the clinical activity of GC. We could not define predictive factors in this cohort, which was probably due to the relatively small number of pts. No significant financial relationships to disclose.