The development of brain metastasis is a late event in the course of colorectal carcinoma and occurs most often in patients with extensive systemic disease that contraindicates surgical resection. Radiotherapy can improve the survival of this group of patients whereas the role of chemotherapy is still unclear due to the low frequency of such cases.

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cisplatin 50 mg/m2 on day 1, gemcitabine starting at 1400 mg/m on days 1 and 8 every 21 days. Subsequent levels were increased by 200 mg/m2. Forty-two patients with metastatic NSCLC were enrolled (37 males; median age 61 years; squamous cell carcinoma 19 patients; performance status 2, in 13 patients; 18 patients had significant weight loss). MTD was found to be 2600 mg/m2 because of DLT in three of six patients: two neutropenic fever and one massive bleeding. Overall toxicity was generally mild consisting mainly of neutropenia. Asthenia was the most common non-hematological effect. Overall response rate was 19 out of 41 patients (46.3%) and median survival was 31 weeks. We conclude that the recommended dose for a phase II dose is gemcitabine 2400 mg/m2 days 1 and 8 as a 30-min infusion when given with cisplatin 50 mg/m2.

Background:The combination of BRAF and MEK inhibitors delays the onset of resistance and provides more sustained and dramatic responses in comparison with a BRAF inhibitor in monotherapy. The objective of the study was to evaluate the effectiveness of the combination therapy with vemurafenib/cobimetinib in terms of durability, and to describe differential characteristics in patients associated to durable responses in real-world settings. Patients and Methods: Retrospective, observational, cross-sectional, multicenter study involving 41 patients with advanced melanoma harboring a BRAF V600 mutation who initiated a combination therapy with vemurafenib/cobimetinib between May 2018 and March 2019. Participants were differentiated regarding the durability of the response: durable (complete response, CR, or a partial response, PR, for at least 12 months) and non-durable (stable disease, SD, progressive disease, PD, or CR/PR <12 months). Secondary endpoints included treatment adherence, labor productivity, anxiety/depression, and safety profile. Results: During the combination therapy, 12 patients (29.3%) had a CR, 19 a PR (46.3%), 5 showed SD (12.2%), and 5 had PD. A total of 12 patients (29.3%) were considered as achieving a durable response and 29 (70.7%) as a non-durable one. Practically all sociodemographic and clinical characteristics were similar between patients. Body mass index was the only differential factor (with higher body mass index achieving a non-durable response). The treatment adherence was 100% in patients with durable response and 66.7% in those with non-durable. Conclusion:The combination treatment with vemurafenib/cobimetinib results in an important impact on long-term survival, leading to a steady CR in one-third of the patients.

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