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BACKGROUND: Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear. METHODS: We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Patients were eligible if they presented with a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score, defined as an Eastern Cooperative Oncology Group performance-status score of 0 (on a 5-point scale, with higher scores indicating greater disability), ascites of less than 500 ml, and complete resection at initial surgery. A positive AGO score is used to identify patients in whom a complete resection might be achieved. The primary end point was overall survival. We also assessed quality of life and prognostic factors for survival. RESULTS: A total of 407 patients underwent randomization: 206 were assigned to cytoreductive surgery and chemotherapy, and 201 to chemotherapy alone. A complete resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.02). Patients with a complete resection had the most favorable outcome, with a median overall survival of 61.9 months. A benefit from surgery was seen in all analyses in subgroups according to prognostic factors. Quality-of-life measures through 1 year of follow-up did not differ between the two groups, and we observed no perioperative mortality within 30 days after surgery. CONCLUSIONS: In women with recurrent ovarian cancer, cytoreductive surgery followed by chemotherapy resulted in longer overall survival than chemotherapy alone. (Funded by the AGO Study Group and others; DESKTOP III ClinicalTrials.gov number, NCT01166737.).

Background Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in two of eight patients with gemcitabine-refractory PDAC. Patients and methods This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC. Patients received gemcitabine 1000 mg/m2 (30-min IV infusion) on days 1, 8, 15 of a 28-day cycle combined with either 100 mg oral dasatinib or placebo tablets daily. The primary objective was overall survival (OS), with safety and progression-free survival (PFS) as secondary objectives. Exploratory endpoints included overall response rate, freedom from distant metastasis, pain and fatigue progression and response rate, and CA19-9 response rate. Results There was no statistically significant difference in OS between the two treatment groups (HR = 1.16; 95% confidence interval [CI]: 0.81–1.65; P = 0.5656). Secondary and exploratory endpoint analyses also showed no statistically significant differences. The burden of toxicity was higher in the dasatinib arm. Conclusions Dasatinib failed to show increased OS or PFS in patients with locally advanced PDAC. Alternative combinations or trial designs may show a role for src inhibition in PDAC treatment.

De nombreux agents incluant les substances cytotoxiques et non cytotoxiques peuvent entrainer une toxicite pulmonaire, qui concerne essentiellement le parenchyme et moins frequemment les voies aeriennes, la plevre et la circulation sanguine pulmonaire. Les symptomes induits par la toxicitede ces traitements sont peu specifiques et peuvent etre difficiles a distinguer de ceux provoques par plusieurs pathologies survenant dans ce contexte de cancer en cours de traitement. Ainsi, le diagnostic est essentiellement realiseapres exclusion de toutes les autres causes possibles de pathologie pulmonaire, et repose aussi sur la relation temporelle entre l’exposition du medicament et le debut des symptomes respiratoires. Les signes cliniques et radiologiques de ces traitements refletent en general le processus histopathologique sousjacent et incluent la pneumopathie interstitielle non specifique, les dommages alveolaires diffus, la bronchiolite obliterante avec organisation pneumonique (BOOP), l’œdeme et l’hemorragie alveolaire. De plus, plusieurs de ces traitements alterent les tests fonctionnels respiratoires des patients. La connaissance de l’ensemble de ces signes et des traitements les plus frequemment incrimines peut faciliter le diagnostic et l’initiation d’un traitement approprie. Pneumotox® (www.pneumotox.com) apporte une information regulierement mise a jour sur les pathologies respiratoires iatrogenes.

Neovascularisation is a key step in tumour growth and establishment of distant metastases. We have recently demonstrated that the thienopyridine SR 25989 an enantiomer of the anti-aggregant clopidogrel (Plavix®) lacking anti-aggregant activity, inhibits endothelial cell proliferation in vitro by increasing the expression of endogenous thrombospondin-1, a natural potent inhibitor of angiogenesis. The anti-angiogenic effect of SR 25989 was further assessed in vitro in a quantitative assay of angiogenesis comprising a fragment of rat aorta embedded in a fibrin gel and in vivo in a pulmonary metastatic model using C57BL/6 mice inoculated in the foot pad with the highly metastatic melanoma cell line B16 F10. SR 25989 induced a dose dependent inhibition of spontaneous microvessel development in vitro reaching half maximal inhibition at around less than 50 μM and caused platelet derived growth factor induced angiogenesis to regress as a function of thienopyridine concentration. In vivo, SR 25989 did not alter significantly the growth rate of the primary tumour in the foot pad and did not inhibit development of inguinal nodes which appeared after amputation. However, the number and size of lung metastases were reduced in treated animals when examined at the time of sacrifice. In addition, the few metastases over 1 mm3 did not show any neovascularisation, as confirmed by negative von Willebrand immunostaining and in contrast to intense vascularisation seen in metastases developed by control mice. These results confirm that SR 25989 possesses potent anti-angiogenic properties and is able to inhibit metastatic dissemination and growth. The lack of effect on the primary tumour and inguinal nodes illustrates the complexity of the mechanisms involved in tumoural neo-angiogenesis and points out the possibility for distinct processes leading to neovascularisation in primary tumour as opposed to metastases. British Journal of Cancer (2002) 86, 803–810. DOI: 10.1038/sj/bjc/6600142 www.bjcancer.com © 2002 Cancer Research UK

In the literature the sensitization of DNA to radiation-induced damage by caffeine has been attributed to an override of the G2/M block. This process was supposed to involve the tumor suppressor gene p53 as it was described that p53 negative cells were more sensitive to checkpoint inhibition by caffeine than the wildtype phenotype. We have recently shown that caffeine does not cause an override of the G2/M block induced by radiation in normal human fibroblasts. We demonstrate here that this also applies to a human transformed cell line, the thyroid carcinoma K1, when submitted to γ- rays irradiation. Within 9 hr after irradiation over 70% of the cells accumulated in the G2/M phase. This block persisted at 16 hr. In caffeine containing cultures the percentage of cells attaining the G2/M phase was reduced by over 30% at 16 hr. This was reflected in an accumulation of the cells in G1 phase and an inhibition of the S phase traverse. Cell cycle analyses from further time points combined with cell proliferation measurements confirmed these data. These results were independent of p53 status as experiments performed with variant K1 cell lines having defective p53 functions, led to similar conclusions. In addition, caffeine restored a G1 delay after irradiation in the cell lines with abrogated p53 functions. The effects of caffeine undeniably cumulate with damages induced by irradiation but probably by inhibiting DNA repair mechanisms or by intervening with purine and pyrimidine metabolisms and not by causing a G2/M block override. © 2001 Wiley-Liss, Inc.

Caffeine has for many years been known to be involved in the sensitization of DNA to damage. One potential mechanism recently put forward is an override of the G2/M block induced by irradiation, which would leave the cells less time for DNA repair prior to mitosis. However, different cell types display a variety of responses and no clear pathway has yet emerged, especially as little is known about the capacity of this agent to enhance DNA damage in normal, untransformed cells. Continuous exposure to commonly used caffeine concentrations (1–5 mM) inhibited the proliferation of normal human fibroblasts (NHFs) in a dose-dependent manner to up to 80% at 5 mM. Exposure of exponentially growing NHFs to UVc radiation (20 J m–2) or γ radiation (2.5–8 Gy) led to a 45–60% inhibition of proliferation and protracted accumulation of cells in the G2/M phase. Addition of 2 mM caffeine after irradiation induced slowing of the S phase passage, with a resultant delay in G2/M accumulation mimicking a G2/M block override. These results were confirmed by stathmokinetic studies, which showed delayed entry of the cells into mitosis in the presence of caffeine. Our data demonstrate that caffeine primarily inhibits replicative DNA synthesis and suggest that, at least in normal cells, caffeine potentiates the cytotoxicity of radiation by intervening in DNA repair rather than by overriding the G2/M block. © 2000 Cancer Research Campaign

Summary Background: Advanced ovarian cancer is often a fatal disease, despite good initial response to chemotherapy. Dose-intense schedules have been reported, but faile

ML18147 evaluated continued bevacizumab with second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) progressing after the standard first-line bevacizumab-containing therapy.Evaluating outcomes according to tumor Kirsten rat sarcoma virus oncogene (KRAS) status was an exploratory analysis. KRAS data were collected from local laboratories (using their established methods) and/or from a central laboratory (mutation-specific Scorpion amplification-refractory mutation system). No adjustment was made for multiplicity; analyses were not powered to detect statistically significant differences.Of 820 patients, 616 (75%) had unambiguous KRAS data; 316 (51%) had KRAS wild-type tumors and 300 (49%) had mutant KRAS tumors. The median progression-free survival (PFS) was 6.4 months for bevacizumab plus chemotherapy and 4.5 months for chemotherapy [P0.0001; HR = 0.61; 95% confidence interval (CI): 0.49-0.77] for wild-type KRAS and 5.5 and 4.1 months, respectively (P = 0.0027; HR = 0.70; 95% CI: 0.56-0.89) for mutant KRAS. The median overall survival (OS) was 15.4 and 11.1 months, respectively (P = 0.0052; HR = 0.69; 95% CI: 0.53-0.90) for wild-type KRAS and 10.4 versus 10.0 months, respectively (P = 0.4969; HR = 0.92; 95% CI: 0.71-1.18) for mutant KRAS. In both analyses, no treatment interaction by KRAS status was observed (PFS, P = 0.4436; OS, P = 0.1266).Bevacizumab beyond first progression represents an option for patients with mCRC treated with bevacizumab plus standard first-line chemotherapy, independent of KRAS status.

Purpose A multicentric, phase II study to evaluate the efficacy and safety of the combination paclitaxel and oxaliplatin in patients with platinum-sensitive recurrent ovarian cancer. Patients and methods Patients received 175 mg/m2 paclitaxel (over 3 h) followed by 130 mg/m2 oxaliplatin (over 2 h) every 21 days for up to nine cycles without hydration or primary granulocyte colony-stimulating factor prophylaxis. Patients had to have an Eastern Cooperative Oncology Group performance status of 0–2 and to have received no more than one prior cisplatin- and/or carboplatin-containing chemotherapy regimen with a platinum-progression-free interval ≥6 months. Results Of the 105 patients enrolled and treated, 98 were eligible. An overall response rate of 81% (79 of 98 patients) (95% confidence interval 71% to 88%) was observed according to RECIST criteria (third party reviewed), and 88% (86 of 98) when this was complemented with CA-125 response. With a median follow up of 43.6 months (range 30.2–64.2) the median progression-free survival was 10.2 months (range 0.3–21.4) and the overall survival 32.4 months. Seven hundred and eight cycles were administered (median seven per patient; range one to nine). A total of 67% of patients experienced National Cancer Institute Common Toxicity Criteria grade 3–4 neutropenia, including 8% with concomitant febrile episode, without treatment-related deaths. Ninety-three per cent of patients experienced neuropathy of grade 1 or more, including 25% with cumulative reversible peripheral neuropathy of grade 3–4. Oxaliplatin doses were reduced in 30 patients due to neurotoxicity. Conclusions The oxaliplatin/paclitaxel combination can be administered in an outpatient setting every 3 weeks without specific measures. The high level of activity and its duration observed warrants further evaluation of this combination in pretreated platinum-sensitive advanced ovarian cancer patients.

Purpose: To determine maximum tolerated dose, safety and efficacy of weekly 24 h infusional 5-fluorouracil (5-FU) combined alternately with oxaliplatin and irinotecan. Patients and methods: Advanced colorectal carcinoma patients in first- or second-line chemotherapy received increasing doses of 5-FU (weekly 24 h continuous intravenous infusion without leucovorin) on days 1, 8, 15 and 22, irinotecan days 1 and 15; and oxaliplatin days 8 and 22, every 35 days. Results: Thirty-four patients received 175 cycles. The median age was 64 years (range 47 – 78). Eighteen per cent of patients had the primary tumor in the rectum, with a median of one disease site (range one to three), and liver involvement in 88% and lung in 38%. Six (18%) patients had chemotherapy for prior advanced disease. The most frequent grade 3 – 4 toxicity was neutropenia (41% of patients), but the regimen was well tolerated clinically, with febrile neutropenia in two patients and grade 4 neutropenia lasting >7 days in one; grade 3 – 4 diarrhea, nausea and vomiting in 6% of patients; grade 3 – 4 peripheral neuropathy in 9% of patients. Seventeen patients had a partial response (50%; 95% confidence interval 33% – 67%), 13 had stable disease and one had progressive disease. Five patients underwent metastatic surgical resection after tumor shrinkage. Median response duration was 14 months (range 4.7– 29.2+) and median time to progression was 11.3 months (range 1.1+ – 30.7+). Conclusions: This combination three-drug regimen is feasible and well tolerated without toxicity overlap. Preliminary antitumor activity compares well with standard double combinations, with an unusually long median time to progression. The recommended dose is 5-FU 3000 mg/m 2 , weekly for 4 weeks, irinotecan 100 mg/m 2 days 1 and 15, oxaliplatin 80 mg/m 2 days 8 and 22. Further assess

The aims of this study were to identify prognostic variables for toxicity and survival in patients with cancer participating in phase I clinical trials and compare characteristics of those treated with cytotoxic chemotherapy (CT) and non-cytotoxic drugs (non-CT). Data were collected from 420 (114 CT, 306 non-CT) patients enrolled in 16 phase I trials (five CT and 11 non-CT trials) in one cancer centre. Analyses of all patients were used to compare treatment groups, identify predictive variables for toxicity and to estimate prognostic factors in overall survival (OS). These were used to develop a prognostic index (PI). Multivariate analysis found those patients with better performance status, fewer sites of metastases, baseline Hb12 g dl(-1) and WBC or LDH in the normal range had significantly better OS. Male gender, platelet count450 x 10(9) l(-1), high WBC or treatment with a non-CT phase I agent significantly reduced the chance of grade 3/4 toxicity. Overall survival was not significantly different between the CT and non-CT groups (260 vs 192 days, P=0.47) except for those with liver metastases (228 vs 137 days, P=0.02). Overall tumour response was 4.9% (95% CI: 2.7-7.0%). The PI identified three distinct patient groups with median survival of 321, 257 and 117 days. In conclusion, entry into a phase I trial of a non-CT drug is a safe option for heavily pretreated patients with cancer. The PI generated from these data can estimate the survival probability for patients entering phase I studies.

Despite high response rates with platinum-based front-line chemotherapy, the prognosis for advanced ovarian carcinoma (AOC) is poor. Salvage chemotherapy for recurrent AOC was of little benefit before paclitaxel as single-agent therapy showed appreciable efficacy. Anthracyclines are effective, but are not often part of first-line therapy. In this pilot study, we investigated the feasibility of an anthracycline plus paclitaxel combination therapy for recurrent AOC. Twenty-four patients received 150 mg/m 2 paclitaxel on day 1, with either 50 mg/m 2 doxorubicin on day 1 or 75 mg/m 2 epirubicin on day 1 every 3 weeks. A 27% overall response rate was obtained. Myelosuppression was the major toxicity, but was manageable. No myocardiac toxicity was observed. We conclude that paclitaxel–anthracyclines is a promising salvage combination therapy in AOC that should be investigated further.

p53 mutations are found in about 70% of human cancers. In order to evaluate the role of these mutations in response to chemotherapeutic agents, it is important to distinguish between p53 response to DNA-damaging agents in normal and in tumour cells. Here, using normal human fibroblasts (NHFs), we show that cisplatin and UV radiation induce G2/M arrest which is temporally linked to p53-protein induction. To study the contribution of p53 to this G2/M arrest, we inhibited p53 induction in NHFs using p53 anti-sense oligonucleotides. Following exposure of NHFs to UV radiation, the inhibition of p53-protein induction leads to a greater accumulation of cells in the G2/M phase, but also to a decreased fraction of cells in the G1 phase. We propose that p53 does not induce G2/M arrest directly, and that the extent of this arrest may depend on the fraction of cells that do not stop at the G1 phase following exposure to DNA-damaging agents. Furthermore, inhibition of p53-protein induction leads to increased sensitivity of NHFs to UV radiation. These results suggest that inhibition of p53 protein enhances sensitivity to DNA-damaging agents in normal human cells.

Background The preparation in advance of anticancer drugs can decrease the waiting time of patients in oncology day units. Purpose To establish a system of phoning patients before their session (D-1 call) to cheque their availability. A year after its deployment, we evaluated the impact of this plan. Materials and Methods The oncologist and a nurse call patients one day before their appointment. The prescriptions are validated when the patient’s condition permits it in the light of the patient’s biological assessment, done in an outside medical analysis laboratory, and an interview using a standardised questionnaire. After pharmaceutical validation, anticancer drugs are prepared in the afternoon for the next day. Indicators of routine monitoring were defined. Results A median of 13 patients with 23 planned day-hospital appointments were called the day before their appointment. An oncologist validated the treatment of 45% of the patients on D-1 and 95% of the cancer treatments were delivered on D1 before 9:00 am. The total time the patients spent in the unit was reduced from 273 minutes to 242 minutes after our plan was adopted. The average time between the end of the medical consultation and the start of the treatment went down from 79 minutes before the D-1 call to 52 minutes. In addition, 2/3 of patients received the treatment only 30 minutes after seeing their doctor. Finally, fewer than 2% of anticipated preparations were not administered. Conclusions The D-1 call requires significant effort, but it enables us to improve the organisation of care in the oncology day unit and the preparation of the anticancer drugs by the pharmacy’s production unit. The workload is more even throughout the day and is not stressful for the staff. All of this contributes to making the system safer. We are hoping to extend the D-1 call to the oncology week unit and evaluate patient satisfaction. No conflict of interest.

Background Study results demonstrated that IFN augments BEV activity and improves median PFS in pts with mRCC. Thus, combination BEV + IFN is a standard first-line treatment option for mRCC. Combining BEV with the mTOR inhibitor EVE may be an efficacious and well-tolerated treatment option. The open-label, phase II RECORD-2 trial compared first-line EVE + BEV and IFN + BEV in mRCC. Patients and methods: Therapy-naive pts with clear cell mRCC and prior nephrectomy were randomized 1:1 to BEV 10 mg/kg IV every 2 weeks with either EVE 10 mg oral daily or IFN (9 MIU SC 3 times/week, if tolerated). Tumour assessments were every 12 weeks. Primary objective was treatment effect on progression-free survival (PFS) per central review based on an estimate of the chance of a subsequent phase III trial success (50% threshold for phase II success). Results In EVE + BEV (n = 182) and IFN + BEV (n = 183) arms, median age was 60/60 years, 76/72% of pts were men, MSKCC risk was favourable/intermediate/poor in 36/57/7% and 36/57/7% of pts, and 43/46% of pts had >2 organs involved, respectively. For EVE + BEV and IFN + BEV, median treatment duration was 8.5/8.3 months, respectively; 23/26% of pts discontinued due to AEs. In EVE + BEV and IFN + BEV arms, median PFS by central review was 9.3/10.0 months (HRIFN/EVE, 0.91; 95% CI, 0.69-1.19; P =0.485), respectively; probability of subsequent phase III success was 5.1%. Results of central and local PFS analysis were consistent. Objective response rate was 27/28% in EVE + BEV and IFN + BEV arms, respectively. Median overall survival (OS) was not reached in the EVE + BEV arm and was 25.9 months (95% CI: 21.1, 30.2) in the IFN + BEV arm. Most frequent AEs (%) were stomatitis (63), proteinuria (49), diarrhoea (39), hypertension (38), and epistaxis (35) in EVE + BEV arm and decreased appetite (45), fatigue (41), proteinuria (37), and pyrexia (35) in IFN + BEV arm. Conclusions In RECORD-2, PFS and tolerability were similar for first-line EVE + BEV and IFN + BEV. Final OS analysis will occur after 2-year follow-up. Disclosure A. Ravaud: Alain Ravaud is a member of global, European, and/or French boards on urological tumors for Pfizer, Novartis, GlaxoSmithKline, Bayer-Schering, and Dendreon, and has received institutional grant support from Pfizer, Novartis, and Roche. O. Anak: Ozlem Anak is an employee of Novartis Pharma AG. D. Pelov: Diana Pelov is an employee of Novartis Pharmaceuticals Corporation. A. Louveau: Anne-Laure Louveau is an employee of Novartis Pharma S.A.S. T. M-H: Tay M-H is a speaker for an advisory board for Novartis Pharmaceuticals Corporation. B. Melichar: Bohuslav Melichar has received honoraria from Novartis and Roche and served on an advisory board for Roche. All other authors have declared no conflicts of interest.

Background Androgen deprivation therapy (ADT) is the standard treatment of hormone-sensitive metastatic prostate cancer (HSMPC). We performed a phase III multicentre trial to compare ADT alone with ADT plus docetaxel (D) in HNMPC. Methods Patients (pts) with HSMPC were randomly assigned to either arm A (ADT + D: 75mg/m q3w, up to 9 cycles) or arm B (ADT). The primary endpoint was overall survival (OS). The planned number of pts was 378 to detect an improvement in OS with a hazard ratio (HR) of 0.62, a power of 80% and an alpha risk of 0.05 (two-sided test). Secondary endpoints were biological progression-free survival (PFS) and clinical PFS. Data on toxicity and quality of life have been previously presented. Results From October 2004 to December 2008, 385pts were included. Baseline characteristics were well balanced between the two arms. Median age was 63 years (43-84), median PSA was 26.4 ng/ml (0.1-11900), Gleason score was ≥ 8 in 57%. Prognostic classification was as follows: good prognosis (49%), intermediate (29%) and poor (22%). The majority of pts had metastases at the time of diagnosis (72%), 28% developed metastases after local treatment failure. Median number of D cycles was 8 (range 0-9). The median follow-up was 50 months (mo) [95%CI: 49-54]. At 6 mo, a higher PSA response (≥ 50%) in arm A (94% vs 85%, p = 0.0096) and a higher PSA progression (≥ 25%) in arm B (10% vs 1%, p = 0.0015) were observed. Biological PFS was significantly longer in arm A: 22.9 vs 12.9 mo, HR; 0.72 [95%CI: 0.57-0.91] (p = 0.005). Clinical PFS was increase in arm A: 23.46 vs 15.44 mo, HR: 0.75 [95CI: 0.59-0.94] (0.015). OS was not significantly different (median: 58.9 mo in arm A and 54.2 mo in arm B, HR: 1.01 [95%CI: 0.75-1.36]. The median OS for each prognostic group was 69.1 [95%CI: 60.9-NR], 46.5 [95%CI: 37.7-NR] and 36.6 [95%CI9: 28.5-58.9] mo respectively in the good, intermediate, and poor prognosis groups (p = 0.001), with no difference between the two arms. At the cut-off time, 65% of pts from the ADT arm had received docetaxel since they developed castrate-resistant prostate cancer. Conclusion Combining docetaxel and ADT improves PFS over ADT alone in pts with HSMPC. However, no difference in OS was observed between the two arms. Disclosure G. Gravis: I have expert testimony to disclose: Sanofi Aventis, uncompensated. K. Fizazi: Participation to advisory boards and speaker for Sanofi-Aventis. F. Joly Lobbedez: advisory board/board of directors position: Sanofi, Roche, Pfizer, Novartis, Ferring; compensated consultant relationship: Roche, Novartis; honoraria: Sanofi, Roche, Pfizer, Novartis, Ferring, Ipsen,Takeda; travel remuneration: ASCO by Novartis, ESMO by Janssen. S. Oudard: I have an advisory relationship and honoraria to disclose: Pfizer Oncology, Bayer-Schering Pharma, Hoffman La Roche, Glaxo SmithKline, Novartis Pharma, Sanofi Aventis. D. Pouessel: Consultant role and honoraria: Sanofi, P. Beuzeboc: Presentations: Avantis, All other authors have declared no conflicts of interest.

7282 Background: Guidelines for lung cancer follow-up are not clearly established and the interest of such a policy is unclear. Methods: A retrospective study of the clinical charts, X-rays and lab tests results of 218 consecutive patients with a diagnosis of primary lung cancer diagnosed between 1999 and 2003 at our institution were reviewed. At the time of treatment completion all patients underwent complete staging and then entered routine follow-up every 3 months for 1 year, every 6 months the second year and then yearly until 5 years. At each clinic visit patients had full clinical examination, complete blood tests, and CT scans of the chest, upper abdomen and CNS. Bronchoscopy was left at the discretion of the physician in charge of the patient. Each visit was assigned by a multidisciplinary panel a score of no evidence of disease (NED), sustained partial response (OR) or tumor control (SD), tumor progression, or second primary cancer. Non-tumoral events were described accordingly. Results: Median a...

5023 Background: OXA is active in mismatch repair (MMR) deficient cells, a condition prevalent in pretreated AOC. OXA/P shows high activity in investigator initiated studies (Faivre et al, Ann Oncol 10:1125, 1999). We evaluated efficacy and safety of OXA/P in AOC pts with clinically evaluable disease pretreated with 1 platinum based regimen ± taxanes and a progression-platinum-free interval (PPFI) ≥6 months (mo). Methods: From Dec 99 to Apr 02, 105 pts, 14 centres received P 175 mg/m2, 3h iv followed by OXA 130 mg/m2, 2h iv, every 3 weeks, for up to 9 cycles (cy) without G-CSF. Median (m) age: 58 years (range 37–83), 96% PS 0/1. PPFI: 69 pts >12 mo, 34 pts 6–12 mo; 80 pts (76%) taxane-pretreated. Results: 708 cy administered; m 7 cy/pt (1–9). Relative dose intensity: OXA 0.95, P 0.97. Efficacy: 98 pts eligible, 7 non-eligible (3 bowel occlusion, 3 >1 prior platinum-based chemotherapy, 2 PPFI not determinable). 98 pts evaluable for response (see table) ORR: 81% (95%CI 71–88), all but 3 responses third part...

5075 Background: Despite the introduction of paclitaxel/platinum combinations in first line treatment of AOC, a small proportion of patients fail to respond. This has been linked to genetic or epig...

In order to assess the possible role of p53 in response to DNA damage occuring in normal quiescent cells, human diploid fibroblasts in confluence for more than two weeks were exposed to ‘UVc irradiation (20 J/m2), with and without p53 antisens oligonucleotides, and time-course cell cycle analysis was performed by flow cytometry for the next 72 hrs. The accumulation of p53 in these irradiated cells at 24th and the inhibition of this induction by p53 antisens oligonuclcotides were, verified by ELISA. After reseeding of control unirradiated fibroblasts, reentry into the cell cycle occured at the 48th hr. In UVc-irradiated cells, absolutly no reentry into the cell cycle was observed. In quiescent irradiated fibroblasts in which p53 accumulation was inhibited by p53 antisens, a reentry into the cell cycle appeared as soon as the 24th, i.e even before unirradiated control cells. These results show that in confluenl normal human diploid fibroblasts, the induction of p53 by a DNA damaging agent creates a complete block and inhibits reentry into the cell cycle. The inhibition of p53 induction not only overcomes this block, regardless of DNA damages, but also permits an earlier reentry into the cell cycle In conclusion, we demonstrate that p53 protein inhibits the reentry into the cell cycle of quiescent normal human fibroblasts exposed to DNA damaging agents. This suggests that p53 could induce a G0/G1block, in addition of a G1/S block which is moreover controversed. To clearly evaluate if this block is a G0/G1 or a G1/S block some more experiments are going on, including p27kipl, p21wafl/cipl and cyclin D expression studies