BACKGROUNDThe aim of this study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of PI3K/AKT/mTOR pathway.PATIENTS AND METHODSIn a prospective, one-arm, phase II study, patients with mRCC received everolimus (10 mg/day) using a 30-day cycle. A prospectively planned evaluation of potential biomarkers of PI3K/AKT/mTOR pathway.RESULTSThe median age of the 58 patients enrolled into the study was 60 years (range 41-78 years). In multivariate analysis, it was found that the adverse independent predictors for everolimus therapy were histological grade G1/2 {hazard ratio (HR): 2.68 [95% confidence interval (CI) 1.29-5.58, P = 0.0082]}, increased lactate dehydrogenase (LDH) level before treatment [HR: 2.55 (95% CI 1.30-4.99, P = 0.0064)] and the PIK3CA gene variant rs6443624 (HR: AC + AA versus CC = 2.08, 95% CI 1 11-3.89, P = 0.0254). In multivariate analysis, it was observed that the adverse independent prognostic factors were: elevated corrected calcium level [HR: 4.17 (95% CI 1.66-10.51; P = 0.0024)] and the PIK3CA gene variant rs6443624 [HR: AC + AA versus CC = 1.97 (95% CI 1.02-3.79; P = 0.0421)].CONCLUSIONSThe PI3KCA gene polymorphism, LDH, and histologic grade can predict the effects of everolimus treatment. The corrected calcium level and the PIK3CA gene variant rs6443624 may be independent prognostic factors. Further investigation is needed to confirm and validate these findings prospectively in other RCC trials.

ABSTRACT Background Qualification of patients with advanced ovarian cancer (AOC) to treatment with primary or interval debulking surgery (IDS) is the subject of controversy. The aim of this study was to assess the expressions of selected proteins of apoptosis to the effects of neoadjuvant chemotherapy (NAC) in patients with AOC. Material and methods We evaluated 60 consecutive patients with AOS (FIGO stage IIIC-IV) treated with NAC, retrospectively. Formalin-fixed, paraffin-embedded tissue specimens were immunohistochemically stained for expression of p53 and survivin in patients given platinum-based NAC undergoing IDS. The expression of survivin was adopted dichotomization by the median expression of the protein found total score (TS) equals 2. For low expression of survivin was TS ≤ 2, while high total score TS> 2 The positive and negative expression of p53 were used to dichotomization study group. Results Median age of 60 patients was 60 years. The optimal IDS was achieved in 69.1% (38/55). We observed significant difference in the percentage of stained nuclei (PS, p = 0.0002), the intensity of staining (IS, p = 0.0003) and TS (p = 0.0001) by comparing the expression of survivin in tumor tissue taken before and after NAC. The expression of p53 in tumor tissue before and after NAC was observed and significant difference was in PS, (p = 0.0424). There were no statistically significant difference in IS and the TS. Expression of survivin and p53 was not related to the results of IDS. Survivin expression was a prognostic factor in AOC patients treated with NAC (p = 0.0484). Expression of survivin and p53 proteins was not a predictor factor in AOC patients. Adverse factors affecting the PFS for AOC patients treated with NAC were: lack of optimal IDS and the lack of an objective response by RECIST criteria (respectively HR was 3.93 (95% CI, 2.07-7.46, p Conclusions High expression of survivin is a useful prognostic factor in patients treated with neoadjuvant chemotherapy for advanced ovarian cancer. This effect is more significant in patients with positive expression of p53. Disclosure All authors have declared no conflicts of interest.

AIMS:The study attempted to evaluate the kinetics of changes in serum TRAIL levels as a potential predictive and prognostic factor in patients with epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC), eligible for an interval debulking surgery (IDS). MATERIAL AND METHODS:17 patients with primary inoperable EOC or PPC in FIGO Stage IIIC or IV who underwent an exploratory operation were enrolled to the study. Serum TRAIL levels were determined by ELISA method (DIACLONE, Besancon Cedex, France) before and after two courses of neoadjuvant chemotherapy (NAC) based on paclitaxel and platinum analogue (cisplatin or carboplatin). The control group consisted of six healthy volunteers. The median difference in concentration of TRAIL (dTRAIL) between the initial marking and after two courses of NAC in each patient was 192 pg/ml and it was used for dichotomization of the test group. RESULTS:Suboptimal interval debulking surgery (IDS) was performed in 23.5% (4/17) and optimal IDS in 76.5% (13/17) patients. TRAIL concentration before chemotherapy did not differ significantly between patients with EOC or PPC [1426.96 +/- 321.06 pg/ml (mean +/- SD) (U = 26, p = 0.08)] and the control group [1160.40 +/- 256.39 pg/ml (mean +/- SD. After two courses of NAC serum TRAIL concentration level was 1247.49 +/- 378.46 pg/ml (mean +/- SD). The difference was significant (Z = 2.44, p = 0.0147). Statistical analysis showed that dTRAIL did not significantly influence either extent of IDS (U = 35, p = 0.0962) or time to progression (log-rank test, p = 0.1185), overall survival (log-rank test, p = 0.1973) and response to treatment according to RECIST criteria (U = 35.5, p = 0.9616). CONCLUSIONS:Serum TRAIL concentration levels changed significantly during NAC. However, it seems that the concentration of this protein has no critical value as a predictive or prognostic factor in patients with EOC or PPC.

16532 Background: Cisplatin is an effective antineoplastic agent, but can cause renal tubular damage. The experimental studies indicate a substantial additive effect of Mg- depletion on cisplatin induced renal toxicity. The aim of this study was to examine the effect of magnesium supplementation on nephrotoxicity after giving the standard cisplatin- based chemotherapy in patient with epithelial ovarian cancer (EOC). Methods: A double-blind, placebo- controlled, randomised study conducted in which magnesium sulphate was administered at a dose of 5 g as an iv infusion before each of course of standard chemotherapy with paclitaxel 135 mg/m2 over 24 h infusion plus cisplatin 75 mg/m2 (PP) every 3 weeks in patients with EOC. Between each of courses and 3 weeks after six of this regiments the patients were administered magnesium subcarbonate at a dose 500 mg three times per day p.o. GFR markers as: serum levels of creatinine, creatinine clearance estimated on Cocroft- Gault (ClCG) and Modification Diet of Renal Disease (MDRD1) formula were recorded before the starting each of the cycles, and 3 weeks after the sixth course. Results: Between January 2003 and January 2006, 41 EOC patients who underwent randomization, 40 were eligible. We noted that serum levels of magnesium significantly varied between supplemented and non- supplemented groups (p<0.0001). The placebo (control) group showed significantly greater slope of GFR assessed by: serum levels of creatinine (p=0.0069), creatinine clearance estimated on Cocroft- Gault (p=0.0077) and MDRD1 (p=0.032) formula than magnesium supplemented group. Neither group showed differences in tumor growth rates or outcome. Conclusions: These results show that magnesium supplementation during chemotherapy with Cisplatin/ Paclitaxel is a nephroprotective management with no reduction of antitumor efficacy. No significant financial relationships to disclose.

16080 Background: Cystatin C is a cysteine protease inhibitor which has been recommended as the marker of glomerular filtration rate (GFR). We investigated significance of cystatin C in relation to ovarian cancer extent and its feasibility in assessment of renal function in patient with ovarian cancer (OC) who underwent chemotherapy. Methods: We prospectively included consecutive patients with OC who underwent chemotherapy : cisplatin 75 mg/m2 plus 24-hour infusion of paclitaxel 135 mg/m2 every three week after surgery. Before chemotherapy serum renal markers were noted as: creatinine (Cr), cystatin C (Cys C), albumin, creatinine clearance (ClCr) calculated by using 24-hour urine collection per 1.73 m2, creatinine clearance estimated with formulas Cocroft- Gault (ClCG) and Modification of Renal Disease (MDRD1), respectively. Results: Between February 2003 and January 2006 37 patients were enrolled onto this study. Median age 54 year (range from 28 to 68). Cystatin C and CrCl weakly correlated (R Spearman= -0.36; p=0,03). There were no correlation between cystatin C and other markers of GFR (serum creatinine, ClCG, MDRD1). We showed correlation between cystatin C and tumor extent revealed by spiral CT- scan (> 1 cm diameter) after surgery (R Spearman= 0.4; p=0.01), and CA 125 (R Spearman= 0.4, p=0.03). Cut-off values were established as medians for both factors, and patients with high and low values had no statistical differences in overall survival (log- rank test, p=0.9). Conclusions: We believe that cystatin C could imply OC extent in patients.This factor weakly was correlated with CrCl, and no correlated with other GFR parameters. No significant financial relationships to disclose.

Chemioterapia dotętnicza (HAI-th)jest leczeniem paliatywnym przerzutów do wątroby w raku jelita grubego (r.j.g). W badaniu dokonano oceny efektywności i bezpieczeństwa podawania 5-fluorouracylu metodą "bolus" poprzez mikrocewnik umieszczony czasowo w tętnicy wątrobowej. Od lipca 1996r. do listopada 2002 roku poddano chemioterapii poprzez tętnicę wątrobową 72 chorym (M-45, K-27), w wieku od 19 do 78 I. (śr.57,9). z przerzutami w wątrobie w przebiegu r.j.g. Chorzy byli w dobrym stanie ogólnym, >60% wg Karnofskiego. Otrzymywali 5-Fluorouracyl (5Fu) 800 −1000 mg/m2 w 100 ml 5% Glukozy + 5.000 j. heparyny + 20 mg dexametazonu poprzez cewnik umieszczony w tętnicy wątrobowej przez okres 15–20 minut pod radiologiczną kontrolą. Leczenie powtarzano co 4 – 5 tygodnie. Podano 458 cykli chth (od 1 do 12), śr. 6,22 na pacjenta. Odpowiedź oceniano wg standardów WHO za pomocą TK. Czas do progresji oraz przeżycia określono przy pomocy metody Kaplan-Meiera dla grupy o niepeł-nej obserwacji. Oceniona toksyczność 235 u,4 chorych po 10 kursach° (51,3%) kursów HAI-th zawierała: małopłytkowość II u 2 chorych po° u 1 chorego po 3 kursach (1,28%), i IV° (4,25%), leukopenię III u 3 chorych po 5 kursach (2,18%), stomatitis III° 7 kursach (297%), gorączkę IV u 1 chorego po 2° u 4 chorych 15 kursach (6,4%), nudności i wymioty III°i IV u 2 chorych po 2 kursach (0,9%). Odnotowano°kursach (0,9%), biegunkę III i IV przedłużone krwawienie z miejsca wkłucia cewnika u 9 chorych (13,2%), u 1 chorego zwężenie tętnicy wątrobowej. u 6 chorych (8,3%) CR, 5 (6,9%) PR, 31 (43%) SD. Średni czas przeżycia od rozpoczęcia HAI-th wynosił 14,24 + 9,54 miesięcy, czas do progresji 8,05 + 4,10 miesiąca. Jeden, dwa i trzy lat przeżyło odpowiednio: 52, 25 i 8,3% chorych poddanych HAI-th. Spośród 72 chorych 54 (75%) zmarło, 18 (25%) nadal żyje. Całkowity czas przeżycia wynosił 18,99 + 11,39 miesięcy. W analizie wieloczynnikowej, wielkość guza > 5 cm i liczba przerzutów w wątrobie > 3 należały do złych czynników prognostycznych. Chemioterapia lokoregionalna (HAI-th) zmian przerzutowych w wątrobie stwarza nadzieję na przedłużenie życia dla wykazanych chorych, u których zostały wykorzystane wszystkie dostępne metody leczenia przeciwnowotworowego.

Leptyna, kodowana przez gen ob [1] jest polipeptydem o wybitnie plejotropowym dzia3aniu: hormonem, wytwarzanym g3ównie przez tkankê t3uszczow1, bior1cym udzia3 w regulacji masy cia3a [2] i stymuluj1cym wytwarzanie estrogenu [3] oraz cytokin1, bior1c1 udzia3 w hemopoezie [4, 5], angiogenezie [6], modulacji wytwarzania cytokin przez limfocyty T pomocnicze [7], regulacji cyklu komórkowego i byæ mo¿e onkogenezie.

A preliminary study has been carried out to compare toxicity and feasibility in operable or metastatic renal cell cancer patients. 11 patients (aged 49-71) with renal cell carcinoma and in a good shape (70-90% Karnofsky's performance status) entered the study. Patients were treated with immunotherapeutic agent - interlukin-2 (IL-2) 6 mln/M-2/V day weekly for VI weeks (immunotherapy arm-4 pts) or with chemoimmunotherapeutics (7 pts): IL-2 20 mln U/m(2) s.c./III-IV-Vd/I week, 5 mln/m2 s.c. /I-III-Vd/II-III week, IFN-alpha-6 mln/m2 s.c./Id/I and IV week, 6 mln/m2 s.c./I-III-Vd/II-III week, IFN-alpha 9 mln/m2 s.c./I-III-Vd/V-VIII week, 5-Fu-750 mg/m2 i.v./Id/V-VIII week.. All enrolled patients have been evaluated by abdominal and thoracic computerized tomography, chest X-ray, sonography. Among documented side-effects were: fever, chills, malaise, diarrhea, rash, hypotension, alopecia in both arms. Both therapy modalities remain non-toxic permanently and feasible for treatment of renal cell carcinoma.