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.

There is evidence that sex hormones and intrauterine factors are involved in the etiology of testicular cancer. We evaluated the importance of perinatal and adult life correlates of sex hormones as risk factors for testicular cancer in a case control study of 97 incident, histologically confirmed cases, residents of the Greater Athens area and environs, who were diagnosed in the 3 specialized cancer hospitals and the major General Hospital in Athens during the 2 year period 1993-94. Cases were age-matched to 2 healthy controls from the same study base. Both cases and controls as well as their mothers were interviewed by the same investigator and the data were analyzed through conditional logistic regression. The odds ratio for testicular cancer was elevated among persons born after a pregnancy characterized by severe nausea. Among the adult life factors, higher body mass was associated with reduced risk, as was evidence of baldness. To the extent that nausea during pregnancy reflects higher levels of pregnancy estrogens on the one hand, and baldness is linked to androgens on the other, our data suggest that estrogens in the intrauterine life and androgens at later stages may have sequential opposing effects for the development of testicular cancer. Int. J. Cancer 71:982-985, 1997.

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The docetaxel-gemcitabine combination is an active and well tolerated salvage treatment in patients with MBC. Previous treatment with taxanes does not preclude a good clinical response to this regimen.

Based on observations of a discrepancy between 'hypersensitivity' reactions to docetaxel (DT) and the clinical features of allergic reactions, we explored the hypothesis that DT-induced acute hypersensitivity reactions (AHRs) have a non-allergic origin. Forty cancer patients receiving DT and 16 patients receiving other potentially allergenic chemotherapeutic agents were included in the study. All DT patients received standard pre- and post-medication. Before, during and after administration of the drugs, clinical symptoms and signs were recorded, and serial blood sampling was performed for the first 2 cycles for all patients or in all subsequent cycles in case of AHRs. Plasma histamine and serum tryptase, two established drug allergy markers, were measured. Seventy-five chemotherapy sessions were evaluable. Nine patients on DT, two on paclitaxel (PT) and one on pegylated doxorubicin experienced an AHR during the first course of chemotherapy. In all cases, heart rate remained stable or increased, while arterial pressure was unchanged or raised; no hypotension or bradycardia was noted. All episodes resolved with discontinuation of drug and did not reappear during a re-challenge with the same agent 30 min later. Tryptase levels were normal in all pre- and post-exposure samples (post-exposure: 11.32+/-35.63 microg/l, normal values <13.5 microg/l). In all but one AHR-free PT, pre- and post-exposure histamine concentrations remained normal (post-exposure: 2.86+/-11.88 nM, normal values <10 nM). No eosinophilia or basophilia was observed. We conclude that 'hypersensitivity' reactions to DT seem not to be histamine or tryptase mediated; thus, their allergenic nature should be questioned. The underlying mechanism may be related to other biological processes such as the release of vasoactive molecules or non-histamine/tryptase-mediated allergy. If the former is demonstrated by further study, the safety of DT administration will be confirmed, and the pre- and post-medication practice might be revisited.