Single-arm phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients over 70 with previously treated metastatic colorectal adenocarcinoma FFCD 1404 - REGOLD.

BACKGROUND: Regorafenib significantly increases overall survival (OS) in patients with metastatic colorectal cancer previously treated but gives toxicities. OBJECTIVES: to assess the efficacy and safety of regorafenib at it's approved dose in the older population. PATIENTS AND METHODS: This multicenter single-arm phase II enrolled patients ≥70 years old after the failure of fluoropyrimidine-based chemotherapy, anti-VEGF, and anti-EGFR treatment. The primary endpoint was disease control rate (DCR) 2 months after initiation of regorafenib (160 mg/day, 3 weeks on/1 week off). RESULTS: Forty-three patients were enrolled, with a median age of 77 years. The 2 months DCR was 31.4% in the 35 evaluable patients. For the 42 patients that received at least one dose of regorafenib, median progression-free survival and OS were 2.2 and 7.5 months. The median time to autonomy degradation and quality of life degradation was 3.1 and 3.2 months, respectively. A grade 3-4 treatment-related adverse events was observed in 35/42 patients, notably: fatigue (45.2%), hand-foot skin reaction (19.0%), hypertension (21.4%), and diarrhea (7.1%). There is a trend to achieve DCR in patients ≤80 years and a trend to discontinue the study due to toxicity in patients with ECOG ≥1, over 80 years and with impaired baseline autonomy. CONCLUSION: Treatment with regorafenib in pretreated patients ≥70 years is feasible and demonstrate similar efficacy that was observed in previous studies in young patients. Fatigue is the most frequent severe adverse event. However, caution should be taken for older patients with ECOG ≥1, over 80 years, and with impaired baseline autonomy.

Re-exploring immune-related side effects of docetaxel in an observational study: Blood hypereosinophilia.

Docetaxel is a major anticancer drug that can induce hypersensitivity reactions leading to deleterious treatment interruptions. Blood hypereosinophilia could be a biological sign, potentially lethal, of delayed visceral hypersensitivity reactions. We hypothesized this biological event is probably underreported. In this prospective observational study, we followed up 149 patients treated with docetaxel monotherapy for breast or lung cancer. For each patient, blood eosinophil counts were recorded during docetaxel treatment and up to 3 months after the end of docetaxel treatment. For all patients, blood eosinophil counts significantly increased under docetaxel chemotherapy (P < 0.01). Seven percent had persistent eosinophilia after the end of treatment. Four patients had blood eosinophil counts over 1000/mm3 with severe cardiac, cutaneous and digestive toxicities, and docetaxel imputability was confirmed using drug-imputability scales. For two of these four patients, tissue biopsies were performed during the time of hypereosinophilia and of severe toxicities. Specific immunostainings and electron microscopy found numerous degranulating mast cells and eosinophils. Our study demonstrated that eosinophilia is frequent under docetaxel and could lead to severe complications, implicating eosinophils and mast cells, and possibly IgE. One way of treating hypersensitivity reactions could be by targeting IgEs with omalizumab, an anti-IgE monoclonal antibody approved for the treatment of severe allergic asthma, and successfully used in food and poison-induced anaphylactic reactions.