Background:Sunitinib (VEGFR/PDGFR inhibitor) and everolimus (mTOR inhibitor) are both approved for advanced renal cell carcinoma (RCC) as first-line and second-line therapy, respectively. In the clinics, sunitinib treatment is limited by the emergence of acquired resistance, leading to a switch to second-line treatment at progression, often based on everolimus. No data have been yet generated on programmed alternating sequential strategies combining alternative use of sunitinib and everolimus before progression. Such strategy is expected to delay the emergence of acquired resistance and improve tumour control. The aim of our study was to assess the changes in tumours induced by three different sequences administration of sunitinib and everolimus.Methods:In human Caki-1 RCC xenograft model, sunitinib was alternated with everolimus every week, every 2 weeks, or every 3 weeks. Effects on necrosis, hypoxia, angiogenesis, and EMT status were assessed by immunohisochemistry and immunofluorescence.Results:Sunitinib and everolimus programmed sequential regimens before progression yielded longer median time to tumour progression than sunitinib and everolimus monotherapies. In each group of treatment, tumour growth control was associated with inhibition of mTOR pathway and changes from a mesenchymal towards an epithelial phenotype, with a decrease in vimentin and an increase in E-cadherin expression. The sequential combinations of these two agents in a RCC mouse clinical trial induced antiangiogenic effects, leading to tumour necrosis.Conclusions:In summary, our study showed that alternate sequence of sunitinib and everolimus mitigated the development of mesenchymal phenotype compared with sunitinib as single agent.

No standard second-line chemotherapy after GEM-platinum failure exists and data on survival benefit remain limited. Material and methods: We retrospectively reviewed patients with recurrent/advanced BTC who received gemcitabine-oxaliplatin (GEMOX)-based chemotherapy followed by 5-fluorouracil-irinotecan (FOLFIRI)-based chemotherapy to evaluate the efficacy of the sequential treatment strategy. Overall survival (OS) and PFS were calculated by Kaplan-Meier method. Results: Fifty-two patients were analyzed, 21 (40%) had intrahepatic, 14 (27%) had hilar/extrahepatic, and 17 (33%) had gallbladder cancer. Median age was 64 years (range 38-79 years). Prior curative intent resection of the primary tumor was performed in 23 (44.2%) patients and GEMOX adjuvant chemotherapy was given in 12 (23.1%) patients. After a median follow-up of 36.3 months, 47 (90.4%) patients completed the treatment strategy. First-sequence GEMOX and second sequence FOLFIRI achieved 4.8 months and 3.2 months median PFS, respectively. The global OS for the sequential chemotherapy was 21.9 months. The sequence of FOLFIRI resulted in a median OS of 8.4 months. Conclusion: The sequence of GEMOX-FOLFIRI is a potential treatment strategy for patients with recurrent/advanced BTC.

Non-small cell lung cancer (NSCLC) is the most deadly cancer in the world. Vinorelbine is an active vinca-alkaloid with a broad spectrum of anti-tumour activity. In particular, it has high activity in NSCLC, where a synergy with cisplatin has been demonstrated. Recently, oral vinorelbine has shown a similar activity and efficacy as compared to the intravenous formulation, giving to the patient an easier way of administration and increasing his comfort. Although surgery remains the best chance of cure for patients with resectable NSCLC, it is now accepted that postoperative cisplatin-based adjuvant chemotherapy significantly improves survival in patients with NSCLC. The combination of cisplatin and vinorelbine is the most active among all the adopted schedules. Patients presenting with locally advanced disease at diagnosis benefit from concomitant chemotherapy with cisplatin-vinorelbine regimen in combination with thoracic radiotherapy. Platinum-based combinations have become the standard of care for treating NSCLC. Vinorelbine–cisplatin combination is one of the proposed doublets for treating advanced, metastatic, NSCLC. Because of its favorable toxicity profile, vinorelbine has become a major compound as a treatment for elderly patients with advanced NSCLC.

Background: Few studies have evaluated the effects of adjuvant radiotherapy (RT)of breast cancer(BC). The relation between the risk of lung carcinoma and radiotherapy have been controversial. Methods and materials: We retrospectively studied 127 patients treated at the Institut Curie with non metastatic breast cancer and lung carcinoma between 2000 and 2011(2/3 of BC apperead befor lung). Confirmation Diagnosis bronchial cancer obtained by: biopsy: histological data:architecture, IHC (HR, HER 2, TTF1), EGFR, Kras statut clinical and radiological Correlation. Comparison with breast tumor Results: BC: median age at diagnosis 54 years, predominatly invasive ductual carcinoma(IDC), lumpectomy 78%, mastectomy 21%. Lung cancer: median age at diagnosis: 63 years, 67 smokers. histology: 52 % Adenocarcinoma, 18.1 % scamous cell carcinoma, 18.1% large cell carcinoma, 13.4 % small cell carcinoma. EGFR mutation in 4.3%. 109 patients underwent RT (3 cases of lung cancer befor BC):Region: internal mammary chain: 46, supracalvicular: 42, axillary: 21. Technique: lateral decubitus position: 44, dorsal decubitus position: 57. Interval between breast and lung cancer: 0–3 years: 24.4%, 3–5 years: 15%, 6–10years: 16.5%, 11–20 years: 28%, >20 years: peak of incidence of lung cancer in the 3 years of diagnosis of breast cancer: 24.4 %. There was no apparent relation between treatment of BC and relative risk of developing lung carcinoma. 2nd peak between 11–20 years: 32 % patients, suggest that RT may increase risk of lung carcinoma (latency period for radiation induced second malignancy). Conclusion: This study suggest that adjuvant RT is associated with a real but small risk of developing lung carcinoma. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-14.