HLA-mismatched natural killer (NK) cells have shown efficacy in acute myeloid leukemia, and their adoptive transfer in patients with other malignancies has been proven safe. This phase I clinical trial was designed to evaluate safety (primary endpoint) and possible clinical efficacy (secondary endpoint) of repetitive administrations of allogeneic, in vitro activated and expanded NK cells along with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients with unresectable, locally advanced/metastatic NSCLC receiving 1st/2nd line chemotherapy were eligible to receive 2-4 doses of activated NK cells from two relative donors. Donor's CD56(+) cells were cultured for 20-23 days with interleukin-15 (IL-15) and hydrocortisone (HC) and administered intravenously between chemotherapy cycles. Premedication with corticosteroids and/or H1 inhibitors was allowed. Sixteen patients (performance status 0-1) with adenocarcinoma (n = 13) or squamous cell carcinoma (n = 3) at stage IIIb (n = 5) or IV (n = 11) receiving 1st (n = 13) or 2nd (n = 3) line treatment were enrolled. Fifteen patients received 2-4 doses of allogeneic activated NK cells (0.2-29 × 10(6)/kg/dose, median 4.15 × 10(6)/kg/dose). No side effects (local or systemic) were observed. At a median 22-month follow-up (range, 16.5-26 months) 2 patients with partial response and 6 patients with disease stabilization were recorded. Median progression free survival and overall survival were 5.5 and 15 months, respectively. A 56% 1-year survival and a 19% 2-year survival were recorded. In conclusion, repetitive infusions of allogeneic, in vitro activated and expanded with IL-15/HC NK cells, in combination with chemotherapy are safe and potentially clinically effective.

BackgroundTargeting angiogenesis is nowadays one of the most promising approaches for breast cancer. Bevacizumab (BEV), a VEGF-trap monoclonal antibody, was recently approved in combination with paclitaxel (PAC) for the first line treatment of advanced breast cancer (ABC). The activity of this combination in pretreated patients is not known.MethodsPatients with pretreated ABC and progressive disease received BEV 10 mg/kg with PAC 135 mg/m2 every two weeks for six months and then maintenance with BEV 15 mg/kg every three weeks until progression. This regimen was chosen for better patient convenience, while maintaining the same dose intensity for both drugs.Results42 patients were reviewed retrospectively (41 f, 1 m, mean age 57 years). Overall response rate was 35.7%. Stable disease was observed in 45.2% of patients, whereas 14.3% of patients progressed. The median overall survival was greater than 20 months, with a one year rate of 83.4%. The median progression free survival was 12.1 months, with a one year rate of 51.8%. Toxicity was in general acceptable.ConclusionThis biweekly BEV/PAC combination seems to be active with acceptable toxicity in pretreated ABC with an advantage over the weekly regimen regarding quality of life and preservation of resources.

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