Germline mutations of the tumour suppressor gene BRCA1 are involved in the predisposition and development of breast cancer and account for 20 -45% of all hereditary cases. There is an increasing evidence that these tumours are characterised by a specific phenotype and pattern of gene expression. We have hypothesised that differences in chemosensitivity might parallel molecular heterogeneity of hereditary and sporadic breast tumours. To this end, we have investigated the chemosensitivity of the BRCA1-defective HCC1937 breast cancer cell line, and the BRCA1-competent MCF-7 (hormone-sensitive) and MDA-MB231 (hormoneinsensitive) breast cancer cell lines using the MTT assay. The 50% inhibitory concentration (IC 50 ) for the individual compounds were derived by interpolate plot analysis of the logarithmic scalar concentration curve after a 48 h exposure. HCC1937 cells were significantly (Po0.005) more sensitive to cisplatin (CDDP) (IC 50 : 30-40 mM) compared with MCF-7 (IC 50 : 60-70 mM) and MDA-MB231 (IC 50 : 90 -100 mM) cells. On the other hand, BRCA1-defective breast cancer cells were significantly less sensitive to doxorubicin (Dox) (IC 50 : 45-50 mM) compared with MCF-7 (IC 50 : 1-5 mM) and MDA-MB231 (IC 50 : 5-10 mM) (Po0.02), as well as to paclitaxel (Tax) (IC 50 : 42 mM for HCC1937, 0.1 -0.2 mM for MCF-7 and 0.01 -0.02 mM for MDA-MB231) (Po0.001). Full-length BRCA1 cDNA transfection of BRCA1-defective HCC1937 cells led to the reconstituted expression of BRCA1 protein in HCC1937/ WT BRCA1-derived cell clone, but did not reduce tumour cell growth in soft agar. BRCA1 reconstitution reverted the hypersensitivity to CDDP (Po0.02), and restored the sensitivity to Dox (Po0.05) and Tax (Po0.001), compared with parental HCC1937 cells. Taken together, our findings suggest a specific chemosensitivity profile of BRCA1-defective cells in vitro, which is dependent on BRCA1 protein expression, and suggest prospective preclinical and clinical investigation for the development of tailored therapeutical approaches in this setting.

1099 Background (TPO)-receptor agonists (romiplostim and eltrombopag) are new therapeutic modalities in the treatment of ITP. Romiplostim treatment was associated with a number of benefits compared with the standard of care in non splenectomized ITP patients: higher platelet response rate, lower rates of treatment failure and splenectomy, fewer bleeding events, and fewer blood transfusions. Nevertheless there are not enough data on the long-term side effects and economic consequences of prolonged treatment. Furthermore, there are no criteria to identify patients potentially cured and that could stop therapy. For all these reasons we have carried out a study of platelet kinetics in all patients treated with TPO- receptor agonists and we have identified a subset who achieved a normal platelet kinetics and that is no longer relapsed two years after discontinuation of the drug Patients and Methods A total of 18 adult patients, female (63%),median (range) age 55 (31 – 78) years, median (range) baseline platelet count 19 (3 – 32) × 109/L.,median of 4 (1 – 7) prior ITP therapies, received romiplostim administered once weekly sc, with dose adjustments to maintain platelet counts in the target range of 50–150×109/L. The median time since ITP diagnosis was 6,8 years (range, 0.6–12.8 years) and 10% had undergone a splenectomy. Patients received romiplostim for a median of 98 weeks (range, 18–104); taking the average weekly dose of all patients, the median was 4 mcg/kg. Home administration was started by 16% of patients (3/18) but 2/3 patients discontinued home administration and resumed weekly outpatient injection. All patients achieved a platelet count ≥50×109/L. Results 3 out of 18 experienced thrombocytosis and rebound thrombocytopenia. A PKS with (111)In oxine-labeled autologous platelets was performed in all patients failing steroid treatment, before romiplostim was started. A gamma function was used for the calculation of platelet mean life span (MLS) that was greatly reduced in 100% of patients.3 patients, who had achieved early a stable platelet count ≥150×109/L. despite the discontinuation of romiplostim maintain normal platelet count after 24 months of follow-up. Stricking a second PKS six months after starting the treatment showed in these subset, a normal platelet half-life with normal uptake on the spleen and liver. Conclusions In our opinion PKS, in romiplostim responding patients who discontinued treatment for the stability of response, may easily detect patients probably cured Disclosures: No relevant conflicts of interest to declare.

Background: Kaposi's sarcoma (KS) is a potentially life-threatening multifocal neoplasm that may represent a difficult therapeutic challenge in disseminated stages. Liposomal anthracyclines, or combination chemotherapy are widely used to treat this kind of patients. The efficacy of taxanes ( paclitaxel and docetaxel), as agents with antiangiogenic properties, has been described previously in the treatment of KS patients butthe length of the infusion, the need for pre-medication with steroids and toxicity caused by solvents -Cremophor EL (CrEL) and polysorbate 80 (Tween80) -can limit their utilization, especially in elderly patients.Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication which can make it easier to tolerate .At the moment there are no studies on its efficacy and safety in older KS patients.

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Chemotherapy-induced thrombocytopenia (CIT) can cause delay or reduction in subsequent courses of chemotherapy. As reported in literature thrombocytopenia occurred in 82% of those receiving only carboplatin, and in 58%, 64%, and 59% of those receiving combination therapies with carboplatin, gemcitabine, or paclitaxel, respectively. Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has been shown efficacy and safety in chronic immune thrombocytopenia (ITP) patients not responding to previous therapy by raising the platelets count in both continued long-term administration and in a repeated short-term administration. Eltrombopag bound the thrombopoietin receptor in the transmembrane region, an area different from where thrombopoietin or romiplostim bound, and activated the thrombopoietin receptor in a different fashion. Here, we report on a series of 18 patients at high risk of CIT because of platinum chemotherapy schedules t who received low doses eltrombopag as prophilaxis Patients and methods: A total of 18 consecutive adult patients, female (60 %), median age 47 years (range 28 -65) were enrolled in the study.The reason of chemotherapy has been ovary cancer in 4 patients, colon cancer in 6 patients relapsed DLBC lymphoma in 4 pts, TNBC in 2 patients, pancreatic cancer in 2 pts. All patients received eltrombopag25 mg by mouth twice a weekly as soon as the platelet count falls below 80000 mmc, and continued on treatment until completion of cycles of chemotherapy. Results and Conclusion: The mean platelet count nadir was 60000 mmc; the number of days with platelet count < 80000/µL was 4 days; The maximum value reached was 270,000 mmc. No treatment-related toxicity was observe. The principal endpoints of the study : avoid nadir platelet counts < 50,000/µL,,platelettransfusions,bleeding events, chemotherapy dose reductions chemotherapy delays. were achieved in all patients. In our opinion low dose eltrombopagprophilaxis can be an effective and safe strategy for preventing the CIT.