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8049 Background: Docetaxel (D) or Erlotinib (E) are registered second-line treatments for EGFR wild type NSCLC. Previous studies suggested a predictive value of the serum proteomic VeriStrat test (VS), assigning a good (VSG) or poor (VSP) classification in second-line therapy of patients (pts.) with NSCLC. EMPHASIS aimed at exploring a predictive interaction in SqNSCLC pts. The trial closed prematurely due to low accrual. Methods: EMPHASIS is a randomized phase III multicenter trial exploring the differential activity of second line E vs D on progression-free survival (PFS) in VSG vs VSP SqNSCLC. The expected hazard ratio (HR) of E vs D was 0.675 for the VSG patients (median PFS, E: 4.0 and D: 2.7 mo.), and 1.23 for the VSP patients (median PFS, E: 2.2 and D: 2.7 mo.). A sample size of 500 was needed to achieve 86% power for testing the expected interaction HR of 1.82 at a two-sided p-value of 0.05. Pts were randomized to receive treatment E150 mg p.o. daily or D 75 mg/m2 i.v. on day 1 of each 21 day cycl...

e18006 Background: Main prognostic factors for survival in NSCLC pts are stage and performance status (PS) while sex, histology and others are reported. However, these variables do not allow predicting individual prognosis, justifying further research. MiRNA are small non-coding RNAs regulating gene expression. As a secondary aim of a prospective study, we looked at the prognostic value of tumour miRNA on survival in NSCLC pts treated by cisplatin (60 mg/m2 D1) and vinorelbine (25 mg/m2, D1+8) 1st line chemotherapy. Methods: During the diagnostic bronchoscopy, a biopsy was lysed into Tripure Isolation Reagent (Roche Diagnostics) on ice, snap frozen and stored at -80°C. MiRNA expression was assessed using TaqMan Low Density Arrays (756 human miRNA panel, Applied Biosystems) and normalized using the delta delta CT method to RNU48 (SNORD48) CT value for every sample. Survival was measured from the registration date. Results: The main characteristics of 38 eligible pts were: median age 60 years, male 27 (71%), 80-100 Karnofsky PS in 26 (68%), adenocarcinoma 20 (53%), stage IV 30 (79%). At time of analysis, 25 pts were dead. After stepwise selection among 756 analysed miRNA, a combination of 4 miRNA including miR-200c, miR-424, miR-29c and miR-124 provided a prognostic signature for survival. Using a linear combination of the miRNA CT values with Cox's regression coefficients as weights, we constructed a prognostic score. With a cut-off of 52, the signature distinguished pts with good (n = 18) and poor (n = 20) prognosis with respective median survival of 47.3 months (95% CI 29.8-52.4) and 15.5 months (95% CI 9.1-22.8) (p st line cisplatin and vinorelbine. These results need confirmation in an independent cohort and the signature has to be compared to conventional prognostic factors.

7055 Background: (Neo)adjuvant cisplatin-based CT demonstrated its activity in improving survival in resectable NSCLC. We aimed to determine if a combination of cisplatin with second-generation drugs (GNP) and a standard neoadjuvant chemotherapy with first-generation drugs (MIP) can be performed in patients with initially resectable stage I-IIIA NSCLC, without reducing the resectability rate. Final results are presented. Methods: Patients with previously untreated pathologically proven stage I-IIIA resectable NSCLC, Karnofsky performance status ≥ 60, adequate haematological, hepatic, renal, lung and cardiac functions were eligible. After central randomisation, patients received three courses of MIP (ifosfamide 3g/m2, mitomycine 6 mg/m2, cisplatin 50 mg/m2) or GNP (gemcitabine 1g/m2 D1-8, vinorelbine 25 mg/m2 D1-8, cisplatin 50 mg/m2). The conclusion of feasibility of each regimen will be drawn if, at least, 50 patients per arm within a sample size of 67 can be completely resected (α 5%, β 20%). Results: F...

3031 Background: Volasertib (V) is a potent and highly selective inhibitor of Plk1, a key regulator of cell-cycle progression. Preclinical data showed that V and Cisplatin (Cis) or carboplatin (Ca)...

7521 Background: Early concomitant chemoradiotherapy is a standard of care in LD SCLC. The primary endpoint addressed by the trial was to look to a survival benefit if cisplatin was administered daily during radiotherapy compared to a standard approach. Methods: Patients with previously untreated pathologically proven LD SCLC, Karnofsky performance status ≥ 60, adequate hematologic, hepatic, renal, lung and cardiac functions were eligible. After central randomization, patients received a first course of E (100 mg/m² D1–3) plus P given either at 90 mg/m² on D1 (arm A) or at 6 mg/m² (D1–5, D8–12, D15–19) (arm B) one hour prior to chest irradiation (15 fractions of 2.66 Gy). Afterwards, all patients received P (90 mg/m² D1) plus E (100 mg/m² D1–3) up to 6 cycles. We planned to randomize 232 patients to detect a 10% increase in 2-year survival rate in the experimental arm (α 5%, β 20%). Results: From 1993 to 2006, 204 eligible patients were randomized (arm A 104, arm B 100), without any significant imbalance ...

19516 Background: Performance status (PS) is a strong independent prognostic factor for survival in patients with advanced non- small cell lung cancer and administration of platinum-based chemotherapy (CT) in patients with poor PS is associated to more severe toxicity. Our purpose was to determine whether poor PS patients (ie those registered with a performance index of 60–70 on the Karnofsky scale) could benefit from CT in terms of clinical improvement defined as reaching, during CT, a PS of at least 80 on the same scale (ECOG PS 0 or 1). Methods: Retrospective analysis of a randomised trial performed in advanced NSCLC where 485 patients received three courses of GIP (gemcitabine + ifosfamide + cisplatin) induction CT, in order to determine the potential clinical benefit of conventional cisplatin-based CT in patients with poor PS defined as 60–70 on the Karnofsky scale. Results: 387 (80%) patients had good PS (Karnofsky 80–100) and 98 (20%) poor PS. Response rates were respectively 38 and 28% (p=0.06), no independent predictive value for PS was found using response to CT as endpoint. Clinical improvement was observed in 25% (95% CI : 15%-38%) of the poor PS patients (respectively 38%, 20% and 14% in case of response, no change and progression, p=0.05). Nine additional patients improved from 60 to 70 during induction CT. Improvement occurred earlier in responders (rates of patients with improvement were 12% after 1 course, 31% after 2 courses and 38% after 3 courses compared to 3%, 5% and 17% in the non responders). Survival of patients with poor PS was significantly worse but survival of responders was similar, whatever initial poor or good PS (logrank test after landmark, p=0.47, HR=1.18, 95%CI: 0.76–1.84 for poor responders). If non fatal toxicity was relatively similar as well as dose intensity delivered after 3 CT courses, there were more toxic deaths (including vascular and cardiac fatalities) in poor PS patients (2.1% versus 9.2%; p=0.002). Conclusions: Although toxicity is increased, combination chemotherapy is associated with clinical improvement in a non negligible rate of patients with poor PS in case of advanced NSCLC. No significant financial relationships to disclose.

7012 Background: Cisplatin-based chemotherapy and taxans are effective treatments for advanced NSCLC. We performed a phase III randomised trial to determine if the sequential administration of cisplatin-based chemotherapy followed by paclitaxel is superior to a cisplatin-based standard chemotherapy, with the use of paclitaxel as salvage treatment. Methods: Untreated advanced NSCLC with adequate PS, hematological, hepatic, cardiac and renal functions were treated by 3 courses of GIP (cisplatin 50 mg/m2, ifosfamide 3 g/m2, gemcitabine 1 g/m2). Patients with a non-progressing tumour were randomised between 3 further courses of GIP or 3 courses of paclitaxel (225 mg/m2). To detect an increase in the survival rates (primary endpoint) from 20% in the GIP arm to 35% in the sequential arm, with 80% probability using a two-sided logrank test with a significance level of 5%, we needed to observe 178 events, requiring to randomise 123 patients in each arm. Results: From January 2000 to February 2004, 485 patients received 3 courses of induction GIP of which 140 were randomised in the GIP arm and 141 in the paclitaxel arm. Median survival times were 14.1 (95% CI: 12.0–16.3) and 16.4 (95% CI: 14.0–18.8) months for the paclitaxel and the GIP arms, respectively (p = 0.17). When treatment comparison was adjusted for the two independent prognostic factors (sex and haemoglobin) revealed by a Cox multivariate analysis, the observed HR was 0.81 (95% CI: 0.63–1.09) in favour of the GIP arm (p = 0.10). There were more grades III/IV thrombopenia with GIP (p< 0.01) and more alopecia with paclitaxel (p = 0.04). Conclusion: Sequential cisplatin-based chemotherapy by paclitaxel does not result in better survival than standard chemotherapy, with the use of paclitaxel as salvage treatment. No significant financial relationships to disclose.

7287 Background:There are with clinical trials problems of external validity due to patients’ selection. Applicability to general population has to be demonstrated. For example, the European Union ...

8198 Background: To assess the role of CVVHDF in cancer patients admitted for ARF in an oncological intensive care unit (ICU). Methods: Retrospective study of all patients with acute renal failure treated with CVVHDF in a medical ICU from a cancer hospital,. Multiple logistic regression was used for multivariate analysis, including all variables with a p value ≤ 0.2 in univariate analysis. Results: From 01/97 until 12/02, 32 cancer patients were treated for ARF with CVVHDF. Their principal characteristics were: male/female 23/9, median age 61 years, haematological/solid tumours 16/16, median APACHE II and IGS II scores 31/67. The number of organ failure was 1/2/3/4 in respectively 10/6/13/2 patients. Sixteen patients died in the ICU and 15 were discharged alive from the hospital. In univariate analysis, variables adversely associated with hospital mortality were: renal failure of renal origin, bone marrow transplant, increasing number of organ failure, reduced lymphocyte count, elevated bilirubin and lowe...