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IF 11.855; International audience

Les cancers du colon atteignent principalement les patients âges. La prise en charge chirurgicale a fait des progres mais l’indication d’une chimiotherapie adjuvante reste controversee. Le choix du schema therapeutique et la selection des patients a traiter est un enjeu majeur. Des essais prospectifs specifiques a la population âgee sont necessaires.

Background In stage III colorectal cancer (CRC), adjuvant chemotherapy (CT) is usually prescribed within two months after curative surgery. Whether or not delaying initiation of CT affects survival is still debated. Material and methods We performed a meta-analysis (MA) of all published studies (full papers or abstracts) comparing delayed CT with standard care. Studies were obtained from a PubMed query (keywords: CRC, adjuvant treatment, delay of CT), a review (Chau et al., 2006), cross-checking references and abstracts from the proceedings of ASCO, ASCO GI and WCGI annual meetings. We chose a cutoff delay of 8 weeks. Risk Ratios (RRs) were calculated from the recorded events (deaths, relapses). We used EasyMA software (fixed-effect model). Results Fourteen studies (including four abstracts) were identified (17,645 patients; 5952 males, 5151 females, mean age 70 years). Of these, three could not be statistically analysed and three used another cutoff (4, 5 or 6 weeks), leaving 8 studies for main MA (13,158 patients; 3932 males, 3644 females, 5942 missing data; 5576 colon cancers, 6677 rectal, 1265 missing data). Delaying CT more than 8 weeks was associated to worse Overall Survival (OS) (RR: 1.20; 95% Confidence Interval (CI) 1.15–1.26). In the MA including all studies whatever their cutoff, longer delay was similarly associated to a worse OS but not a worse Relapse-Free Survival (RFS) (five studies). Conclusion Adjuvant chemotherapy should be started within 8 weeks after surgery. Delaying the initiation of adjuvant CT for more than 8 weeks after surgery significantly decreased OS but not RFS. This discrepancy might be due to factors not directly related to cancer (post-operative complications, social status) or to a more accurate appraisal of death.

Arterial hypertension (HT) has been reported in all studies involving bevacizumab, an antiangiogenic agent designed to target vascular endothelial growth factor (VEGF). The mechanism underlying bevacizumab-related HT is not yet clearly understood. As far as endothelial dysfunction and microvascular rarefaction are hallmarks in all forms of HT, we tested the hypothesis that anti-VEGF therapy could alter the microcirculation in nontumor tissues and, thus, result in an increase in blood pressure (BP). We used intravital video microscopy to measure dermal capillary densities in the dorsum of the fingers. Microvascular endothelial function was assessed by laser Doppler flowmetry combined with iontophoresis of pilocarpine (acetylcholine analogue). All measurements were carried out in 18 patients before and after a 6-month treatment with bevacizumab (mean cumulative dose: 3.16 +/- 0.90 g). Mean BP was increased after 6 months of therapy compared with baseline, from 129 +/- 13/75 +/- 7 mmHg to 145 +/- 17/82 +/- 7 mmHg for systolic BP and diastolic BP, respectively (P < 0.0001). Compared with the baseline, mean dermal capillary density at 6 months was significantly lower (75 +/- 12 versus 83 +/- 13/mm(2); P < 0.0001), as well as pilocarpine-induced vasodilation (P < 0.05). Thus, bevacizumab treatment resulted in endothelial dysfunction and capillary rarefaction; both changes are closely associated and could be responsible for the rise in BP observed in most patients.

We performed a meta-analysis of all published studies relating intratumoural microvessel density (MVD) (45 studies) or vascular endothelial growth factor (VEGF) expression (27 studies), both reflecting angiogenesis, to relapse free (RFS) and overall survival (OS) in colorectal cancer (CRC). For each study, MVD impact was measured by risk ratio between the two survival distributions with median MVD as cutoff. Eleven studies did not mention survival data or fit inclusion criteria, six were multiple publications of same series, leaving 32 independent studies for MVD (3496 patients) and 18 for VEGF (2050 patients). Microvessel density was assessed by immunohistochemistry, using antibodies against factor VIII (16 studies), CD31 (10 studies) or CD34 (seven studies). Vascular endothelial growth factor expression was mostly assessed by immunohistochemistry. Statistics were performed for MVD in 22 studies (the others lacking survival statistics) including nine studies (n = 957) for RFS and 18 for OS (n = 2383) and for VEGF in 17 studies, including nine studies for RFS (n = 1064) and 10 for OS (n = 1301). High MVD significantly predicted poor RFS (RR = 2.32 95% CI: 1.39-3.90; P0.001) and OS (RR = 1.44; 95% CI: 1.08-1.92; P = 0.01). Using CD31 or CD34, MVD was inversely related to survival, whereas it was not using factor VIII. Vascular endothelial growth factor expression significantly predicted poor RFS (RR = 2.84; 95% CI: 1.95-4.16) and OS (RR=1.65; 95% CI: 1.27-2.14). To strengthen our findings, future prospective studies should explore the relation between MVD or VEGF expression and survival or response to therapy (e.g. antiangiogenic therapy). Assessment of these angiogenic markers should be better standardised in future studies.

The area of biological and targeted therapies exploded in the late 1990s. After obtaining good results in hematological malignancies, cancer treatment is now being based on monoclonal antibodies. ASCO has integrated various areas of biological therapy into its scope of clinical activity. Trastuzumab (Heceptin) and bevacizumab (Avastin), antibodies targeting HER-2 and vascular endothelial growth factor, respectively, were approved by the United States Federal Drug Administration for first-line treatment of metastatic breast and colorectal cancer in combination with chemotherapy. Bevacizumab is the first approved agent to target tumor angiogenesis. This drug is now combined with chemotherapy to treat breast, lung, and colorectal cancer. In the past several years, significant advances in the underlying biological mechanisms of renal cell carcinoma, particularly the role of tumor angiogenesis, have made it possible to design molecularly targeted therapeutics. This meeting review is organized by tumor type and biotherapy modality.

A microsatellite instability (MSI) phenotype is found in about 12% of colorectal cancers (CRCs) and is associated with a low recurrence rate after curative surgery. Several studies have identified clinical and pathological factors predictive of recurrence in resected CRC, but not in the MSI subgroup.This multicentre retrospective study included patients with stage I, II or III MSI CRCs. Disease-free survival (DFS) was calculated with the Kaplan-Meier method. Factors associated with DFS were identified in univariate and multivariate Cox analyses.We studied 521 patients with MSI CRC. Respectively 11%, 51% and 38% of patients were at stage I, II and III. Mean age was 68.7years and 36% of the patients received adjuvant chemotherapy. Median follow-up was 32.8months. The disease recurrence rates were 6% and 21% in stage II and III patients, respectively. The 3-year DFS rate was 77%. In univariate analysis, age, bowel obstruction, lymph node invasion, stage T4, vascular emboli, lymphatic invasion and perinervous invasion were associated with poorer DFS (P0.05). Three relevant independent predictors of poor DFS were identified in multivariate analysis, namely bowel obstruction (HR=2.46; 95%CI 1.31-4.62, P=0.005), vascular emboli (HR=2.79; 95%CI 1.74-4.47, P0.001) and stage T4 (HR=2.16; 95%CI 1.31-3.56, P=0.002).Bowel obstruction, vascular emboli and stage T4 are independently associated with MSI CRC recurrence, suggesting that screening for vascular emboli in routine clinical practice may assist with adjuvant chemotherapy decision-making.

Small bowel adenocarcinoma is a rare condition with poor prognosis. Like colorectal cancer, small bowel carcinoma may be a part of genetic syndromes with carcinogenetic pathways different from sporadic forms. We report a case of 41-year-old man with small bowel carcinoma revealing hereditary non polyposis colorectal cancer (HNPCC) syndrome. This report supports the systematic study of the MSI status in every patient with a small bowel carcinoma below 60-year-old of age in order to screen for HNPCC syndrome even in the absence of a family history of related cancers.

Background Tyrosine-Kinase Inhibitors (TKIs) markedly improve Progression Free Survival (PFS) of advanced NSCLC patients mutated for Epidermal Growth Factor Receptor (EGFR). Results on Overall Survival (OS) are more questionable. Therefore, we performed a publication-based meta-analysis to further assess this issue. Methods We did a PubMed query using keywords simultaneously (lung neoplasm, TKI, EGFR mutation, survival). We also searched for relevant abstracts in proceedings of ASCO, ESMO, WCLC annual meetings. We cross-checked all references from all articles. Only phase III randomized controlled trials comparing TKI and chemotherapy were included. We used EasyMA software. Results The 6 eligible studies included 2223 patients (516 males, 1688 females, mostly Asian, median age 60 years, 2155 adenocarcinomas (97 %), 996 mutated tumors, 389 stage IIIB, 1572 Stage IV (71 %), 1989 never smokers (89.5 %). Four studies assessed gefitinib, 2 erlotinib. Chemotherapies were doublets including a platinum salt. Four studies included only mutated patients. Compared to chemotherapy, EGFR TKIs significantly improved PFS (HR = 0.39, 95 % CI 0.28-0.53, random effect model). Conversely, OS was similar among patients who first received TKI or chemotherapy (HR = 1.00, CI 0.83-1.22, fixed effect model). PFS was significantly worse among non mutated patients in the 2 studies including both mutated and wild-type EGFR patients, whereas OS was unchanged. Concerning side-effects, rash, diarrhoea and interstitial lung disease were significantly more frequent after TKI (RRs 5.00; 2.40 and 6.07). As expected, fatigue (RR 0.41), nausea/vomiting (0.19) and haematological disorders were all significantly more frequent after chemotherapy (RRs for neutropenia, thrombocytopenia and anaemia 0.08; 0.18 and 0.26). Conclusions The major discrepancy between a markedly improved PFS and a similar OS after TKI compared with chemotherapy could be related to the high level of crossing-over between the 2 groups. We found no detrimental effect on OS of TKIs among wild-type patients. Disclosure All authors have declared no conflicts of interest.

Introduction: The prevalence of cancer increases with age, and pain is one of cancer's most frequent and disturbing symptoms. Numerous studies have evaluated various treatment approaches, but how pain and symptoms are assessed and managed in elderly people with cancer is unclear. Objectives: The purpose of this study was to estimate the prevalence of pain and to evaluate the adequacy of pain management in elderly patients with cancer. Methods: Using medical charts, we screened all patients with malignant disease, admitted to the geriatric oncology unit, and evaluated by means of CGA to determine the optimum treatment, between January 2011 and January 2013. Demographic data, characteristics of the cancer, reported pain, geriatric data, and analgesic treatment were collected for each patient. Results: 311 elderly patients with cancer were assessed. Median age was 84 ± 6.2 years [66–100]. Patients were predominantly female (60%). The most frequent locations of malignant disease were breast (24%), gastrointestinal (22%), lung (20%), and haematological (16%). Prevalence of reported pain was 44% (137 patients). The highest pain prevalence was observed in gastrointestinal cancer patients (48%). Metastatic patients have significantly more pain, (OR = 4.26, CI 95%: 2.61 – 6.96). 75% of patients with bone metastasis (n = 33/44) experienced pain, (OR = 6.31, CI 95%: 3.04–13.08). Among patients with low cognitive performance (n = 61), only 18% reported pain. Analgesics were prescribed in 197 patients (63%). Only 7% of overall patients received WHO level 3 drugs. Conclusion: This study clearly reports a high prevalence of pain and reduced drug prescribing and treatment among elderly patients with cancer. This issue appears to be most critical among people with severe dementia. Older individuals were less likely to receive any analgesia, especially morphine or another WHO level 3 drugs. The lack of prescription is probably linked to under assessment of pain and fear of adverse effects. Disclosure of interest: None declared.

7547 Background: Chemotherapy (CT) of elderly patients with advanced non small cell lung cancer (NSCLC) is still a matter of debate. Methods: PubMed query, using keywords simultaneously: NSCLC, age...

e17528 Background: We aimed to evaluate metabolic tumor volume (MTV) in comparison to SUVmax measurement as markers of histopathological response to neoadjuvant chemotherapy in locally advanced NSCLC. Methods: Twenty-two patients (18 men; median age:64 years) with locally advanced NSCLC received neoadjuvant platinum-based chemotherapy and, if considered resectable, proceeded to surgery (14/22). Patients had FDG-PET/CT scans before and after 3 cycles of chemotherapy. SUVmax and MTV (40%-SUVmax and adaptive-threshold methods) of the primary tumor were measured (DOSIsoft Software). SUVmax was graded using EORTC criteria. Pathological response was defined as: non-responders, partial responders (>10% residual tumor cells) and pathological responders (

e14005 Background: Microsatellite instability (MSI) results from defective mismatch repair and is observed in 15–20% of colorectal cancers (CRCs). Patients with MSI do not benefit from 5-fluorourac...

7625 Background: In the elderly (age > 70) with advanced non-small cell lung cancer (NSCLC), the relative risk-to-benefit ratio of chemotherapy (CT) administered as single-agent or doublets (includ...

4121 Background: Microsatellite instability (MSI) is a prognostic factor in colorectal cancer. Whether it predicts the effect of adjuvant chemotherapy (CT) on overall survival (OS) and relapse-free survival (RFS) is controversial. Methods: Studies were identified by an electronic search using online PubMed, with simultaneous keywords (colorectal neoplasm, microsatellite instability, chemotherapy, prognosis). Abstracts from ASCO and AACR proceedings were reviewed. Articles were obtained from cross-checking of references and from a previous prognostic meta-analysis (MA) (Popat, 2005). We used EasyMA software, available online. A Hazard Ratio (HR) < 1 for MSI-high (MSI-H) status compared with microsatellite stable (MSS) meant a better survival. Results: Our MA found 21 studies (4 abstracts). Statistical calculations were performed in 11 studies (5087 patients including 2879 receiving 5FU-based CT; mean age: 63 years; 1489 stage II, 2648 stage III (64%)). MSI-H was found in 644 patients (15% of total), MSS in 3624. Seven studies (2 randomized) assessed 2 cohorts receiving or not adjuvant CT, 4 studies only included patients receiving CT. Global HR OS (9 studies) was 0.79 (95% confidence interval or CI: 0.64–0.98; p = 0.03). Global HR RFS (8 studies) was 0.67 (95% CI: 0.54–0.83; p < 0.001). A MA on stage III patients (4 studies, 719 patients, 137 MSI-H) found a higher survival among MSI-H than MSS patients receiving CT (HR OS: 0.71, 95% CI 0.49–1.03; HR RFS 0.56, 95% CI 0.42–0.75). Interaction between MSI status and CT status was statistically significant on OS and RFS (4 studies). A MA among MSI-H patients (7 studies) found no survival difference between patients under CT or not: HR OS: 0.70 (95% CI 0.44–1.09), HR RFS: 0.96 (95% CI: 0.62–1.49). Conclusions: Adjuvant CT significantly improved survival in MSI-H compared with MSS patients. MSI-H stage III patients receiving CT survived more than MSS. MSI-H status did not predict response to CT compared with no treatment. No significant financial relationships to disclose.

e15068 From 04/2002 to 12/2004, and 03/2006 to 08/2008, two consecutive steps were conducted in ACRC patients with chemotherapy alone for the step 1 and with Cetuximab and Bevacizumab for the step 2. Treatment schedule: oxaliplatin (0) 130 mg/m2 D1 over 4 to 6 hours, capecitabine (X) 1000 mg/m2 bi daily D2 to 15, 1 week rest. Cetuximab D1 at cyle 1 and at D2 at cycle 2(400 mg/m2 loading dose, then 250 mg/m2 every week), bevacizumab 7.5 mg/Kg D2 at cycle 1 and at D1 for the cycle 2. At cycle 3 cetuximab and bevacizumab were given at D1. PK analysis were performed at cycles 1 and 2, days 1,2,15,22 and 23. In the step 1, 23 pts were included, M/F = 9/14, M. age 57, PS 0–1-2 = 14/6/3, 1st line /2/3 = 18/4/1. Eleven responses were obtained (4 CR and 7 PR) 2 pts were in CR after hepatectomy, ORR = 48 %( intent to treat). In the step 2, 18 pts were included, M/F = 11/7, M. age = 55, PS 0–1-2 = 8/7/3, 1st line/2 = 17/1.Status K-RAS mutated/wild = 2/13.Seven pts responded to therapy: 1 CR, 6 PR and 1MR for an ORR of 38 %(intent to treat) 3 pts were in CR after hepatectomy and 6 pts were in SD, tumor control in 16/18 pts=88 %.Toxicity was mild, only 1 pt had G3 diarrhoea, 1pt G3 acne, 1pt had G3 neurotoxicity with need oxaliplatin discontinuation after 14 cycles. One pt had fatal pulmonary embolism at first cycle. PK results in plasma ( 14 pts in step 1 and 12 pts in step 2):no statistical differences between X and its metabolites on D2 and 15. Urinary elimination is about 2 % of total dose administered over 4 hours for 5- FU and 8 to 22% for Fluoro β Alanine (FBAL). Plasma clearance of 1.73±1.22ml/h/m2 for 5FU, 53.76±25.36ml/h/m2 for FBAL. For O, residual level at D15 higher in erythrocytes than in plasma suggest an important irreversible binding with red cells without blood toxicity. Conclusions: Xelox with and without targeted therapies is an active and safe combination in ACRC. When O is administered over a long period of time and X is given at least 12 h later, neurotoxicity was mild and no hand-foot syndrome was observed. Important PK parameters variability mainly for 5FU and FBAL suggest posology adaptation on the basis of concentration ratio 5FU/FBAL in blood. No PK interaction between monoclonal antibodies and X or O were observed whatever the schedule of drug administration. No significant financial relationships to disclose.

4077 Background: Curative treatment of liver metastases from colorectal cancer (CRC) relies upon R0 surgery whenever feasible (5-year survival: 40 %). Whether or not addition of adjuvant systemic o...

20746 Background: Some of the patients receiving palliative treatment need social care as well as an adapted medical care. These cases are weekly debated in an interdisciplinary board with participants involved in different specialities (physicians, nurses, psychologists, social workers and dieticians). In this work, we display the results of a survey which evaluates the relevance of interdisciplinary boards aimed to a better taking into care of our patients. Methods: An investigation conducted during 16 months since the initiation of interdisciplinary boards in the medical oncology of the Avicenne Hospital. An anonymous questionnaire including 15 items was submitted for every subject to the staff in charge of the patient’s care. Results: 19/34 of interdisciplinary participants filled in the questionnaire. Among them, 14 attended at least once the interdisciplinary boards (73%). 5 specialists didn’t attend the boards owing to: lack of availability (40%), the day of the board not suitable (40%) and lack of...

4117 Background: Microsatellite instability (MSI) status is a prognostic factor in colorectal cancer (CRC), but its ability to predict chemotherapy (CT) efficacy either in adjuvant or metastatic se...

Background: More than half of cancers occur after the age of 65 and this should grow progressively. Unfortunately elderly people are rarely included in therapeutic surveys and in screening tests, so they miss optimal treatment of their cancer (surgery, chemotherapy, radiotherapy) most of the time. At the Ambroise Pare academic hospital, a 440 beds urban hospital, a geriatric intervention team (GIT) has been created since February 2004. One of its aims is to help others specialists to assess the better treatment for their patients. Patients: In 3 years, 2800 evaluations were done by the GIT in the whole hospital, 234 on inpatients of the pneumology department. On those, 53 were hospitalised for the diagnosis or the treatment of a cancer. Results: Patients average age was 80±6 years old, 53% were female. The mini-GDS was positive in 53% and a time and space disorientation was observed in 41%. 67% patients had cognitive troubles, with high risk of falls for 86%. In 28%, patients received a chemotherapy. In the end, 4 groups of patients could be observed “primary” (2%) who will have an optimal treatment “intermediate” (37%) at whom will be proposed an adjusted treatment “secondary”(50%) who will have a symptomatic treatment “near death” (11%) with palliative care Conclusion: This collaboration have afforded us to identify better patients likely to receive an optimal treatment. The main contribution of the EIG in this collaboration was to afford a fast geriatric assessment to the others physicians in order to make up one’s mind to the best treatment.

3557 Background: Bevacizumab in combination with chemotherapy is the standard treatment of metastatic colorectal cancer (mCRC). Hypertension (HT) has been reported in all studies, in particular grade 3 HT (3 - 16%) (Saif and Mehra, 2006 Expert Opinion on Drug Safety). The mechanism underlying bevacizumab-related HT is not yet clearly understood and recent studies have demonstrated that humoral factors involving the renin-angiotensin system and the sympathetic nervous system had little role in the observed increase in BP. As far as microvascular rarefaction has been reported in all forms of human and experimental HT, we tested the hypothesis that anti VEGF therapy could induce microvascular rarefaction in non tumoral tissues and, thus, result in an increase in BP Methods: For 16 patients treated for mCRC, Bevacizumab was administered at 5 or 7.5 mg/kg every 2 or 3 weeks depending on the frequency of concomitant chemotherapies which were FOLFIRI (4 patients) or XELOX (12 patients) We used intravital video-microscopy to measure basal and maximal (during venous congestion) skin capillary densities in the dorsum of the fingers. Aortic stiffness was evaluated using pulse wave velocity, and microvascular endothelial function was assessed by laser-Doppler flowmetry combined with iontophoresis of three different doses of acetylcholine (ACh). All measurements were performed in 16 patients (mean age: 59±10 y) before and after a 6 month treatment with bevacizumab (mean cumulative dose: 3.16±0.90 g) Results: are summarized in the following table : Conclusions: Pharmacological blockage of VEGF receptors result in endothelial dysfunction and capillary rarefaction in humans. Both changes are closely associated with and seem responsible for the rise in blood pressure observed in patients receiving this treatment. This could be considered for future study about anti- angiogenic treatment and HT. [Table: see text] No significant financial relationships to disclose.

15065 Background: Gem is the only approved chemotherapeutic drug in the treatment of APC. Do as single agent has shown some activity. Effective cytotoxic combinations with gem are urgently needed. Methods: Combination of Gem 1200 mg/m2/d1 + Do 50 mg/m2/d1 every 2 weeks was evaluated in first line APC pts with Karnovsky Index (KI) > 40, and good organ function. Initial Do dose was modified according to liver biology alterations. Treatment of relapse with Gem-Do or other combinations was allowed. Results: The 45 pts (male=64%) included in 7 centres had a median age of 62 yrs (range 36–81 yrs) and 26 (58%) had metastatic disease. Pts received a median of 4 cycles (0–6) with a median dose of 47 mg/m2 for Do and 1170 mg/m2 for Gem. Neutropenia Gr 3/4 was the most severe toxicity (Tox) (24% of pts) and required G-CSF support, with infection G3 in 14 pts (31%), febrile neutropenia in 1. Others G3 Tox were fatigue (20% of pts), diarrhea (14%), anemia (9%) thrombopenia (7%) and G2 Tox: alopecia (33%), nausea (15%) and edema (11%). During treatment, KI improved or was stable in 33% and 44% of pts, weight increased or was stable in 38% and 23%, pain control was better or stable in 20% and 56%. After panel review, objective RECIST response was observed in 17.7% of pts (CR = 4.4%) and stable disease in 40%. Median progression- free survival (PFS) was 3.8 months (mo) and 14 pts (31%) had PFS between 6 and 14 mo. Median survival was 12.0 mo (95% CI; 10.2–13.8 mo). Conclusions: The combination of Do and Gem every 2 weeks is feasible and should be associated with systematic growth factor support. Subjective and objective criteria of efficacy in APC are encouraging. A direct comparison with Gem single agent is warranted. No significant financial relationships to disclose.

14131 Background: Gastric cancer is often diagnosed in locally advanced or metastatic stages and prognostic is particularly bad. Results of a Phase II study of oxaliplatin, fluorouracil, and folinic acid was previously published (Louvet et al, J Clin Oncol. 20:4543–8, 2002). Grade 3 peripheral neuropathy occurred in 21% of patients (oxaliplatin-specific scale). Seven patients withdrew because of treatment-related toxicity. For these patients, tolerance of chemotherapy must be considered. Ca/Mg infusions seem to reduce incidence and intensity of acute oxaliplatin-induced symptoms and might delay cumulative neuropathy (Gamelin et al, Clin Cancer Res 15: 4055–61, 2004). Methods: In this study, in our medical Oncology department, we treated a first group of patients with FOLFOX 4 and a second group with FOLFOX S (FOLFOX S: LV5FU2 Simplified (Folonic acid 200 mg/m2, 2h, 5FU 400 mg/m2,bolus, 5FU infusion 1200 mg/m2, 44h) + oxaliplatin: 85 mg/m2, 2h, d1-d15) combined with infusions of Ca gluconate and Mg sulfate (1 g) before and after oxaliplatin and then we evaluated efficacy and toxicity. Results: Of the seventeen patients with advanced and/or metastatic stomach carcinoma enrolled between August 2000 and December 2004: Median age was 59 range (26;73) years, 12 were male, 5 female with a WHO performance status (PS) No significant financial relationships to disclose.

3685 Background: This trial was conducted to establish potential PK interactions between X and O when administrated in combination (XELOX regimen) and to evaluate neurotoxicity when O is administer...

7348 Background: Gefitinib (Iressa), an inhibitor of the intracellular tyrosine kinase domain, has demonstrated useful activity in advanced pre-treated NSCLC (IDEAL I/II). Methods: Patients (pts) were treated with gefitinib 250mg/day. Endpoints included time to treatment failure (TTF). Results: 33 patients were assessed: median age (range), 61 (38–82) years; male/female, 21/12; performance status (PS) 1/2, 11/22; advanced disease (III A/IIIB/IV) 1/1/29, 31 pts were treated; median number of prior chemotherapy regimens (range), 3(1–4). 31 patients were treated and evaluable for time to Failure (TTF) according to PS status: 4.8 months (PS 1) and 5 months (PS 2). Median duration of disease control (stable disease and symptom control) was 4.9 months. Median TTF for Patients with bronchoalveolar adenocarcinoma (BAC) and adenocarcinoma (n=18) was 4 months and 3 months for patients with squamous-cell carcinoma and large cell carcinoma (n= 13). One patient treated for BAC with leptomeningeal carcinomatosis was fr...

4208 Background: Gemcitabine, the standard chemotherapy for pancreatic cancer, offers modest improvement of tumor-related symptoms and marginal advantage of survival. New approaches, alone and in combination with gemcitabine, are being developed. So we assess the efficacy and toxicity of combination therapy with gemcitabine and docetaxel in patients with unresectable pancreatic carcinoma. Methods: Thirty-one patients (pts) with unresectable, biopsy proven, pancreatic carcinoma were eligible for this study. Patients received docetaxel either 50 mg/m(2) or 35 mg/m(2) regarding hepatic enzyme levels, followed by gemcitabine 1,200 mg/m(2) biweekly until progression or intolerable toxicity. The primary study endpoint was objective response rate. Results: The median age of pts was 60 years (range, 42–81). Male/female ratio was 22/9. Out of the 31 eligible patients, 20 patients were evaluable for response rate. After 2 cycles (2 months), 4 patients had a partial response (20%) and 7 patients had a stable disease...

9641 Background Tumor-induced angiogenesis is a central pathogenic step in the process of tumor growth and metastasis. The aim of this study was to determine whether angiogenesis, quantified with V...

7250 Background: A wide range of chemotherapic agents used singly or in combination have been evaluated in MPM. Doublets with gemcitabine and a platinum salt emerge as one of the most promising reg...

The activity/safety profile of TXT in heavily pretreated MB pts is of interest to the practicing oncologist. Pts char From Aug 1994 to Feb 1995, 29 women with heavily pretreated MBC, have received TXT: 24 pts with 100 mg/and 5 pts with 70 mg/sqm q 3 weeks given with steroids premedication: median age 53 years [42–75]; PS (WHO) 0–1: 16 pts (55%), 2: 9 pts (31%), 3: 4 pts (14%), median time diagnosis first relapse: 28 months (m) [1–216]; median time first relapse/TXT: 40 m [1–164]; Metastatic Sites: liver: 17 pts (58%), bone: 16 pts (55%), lung: 14 pts (48%), skin: 12 pts (41%), lymph nodes: 2 pts (6%), CNS: 4 pts (14%), miscellaneous: 1 (3%). Number of sites/pt: 1: 6 pts (20%), 2: 13 pts (45%), ≥ 3: 9 pts (31%); CA 15-3 was increased in 20 pts (68%). Median nb previous chemotherapy (CT) Unes: 4 [2-11], with anthracyclines 27 pts (93%); 16pts (55%) had also Mitoxantrone; previous hormonotherapy in 25 pts (86%). Toxicity 123 cycles (cy); median (cy) nb/pt: 4 [1–10]; 84 (cy) and 28 (pts) evaluable for hematol Tox, 13 cy (23%) grade III and 44 cy (52%) grade IV neutropenia, 5 cy (6%) grade III–IV thrombocytopenia; 106 cy and 28 pts evaluable for non hematol Tox: asthenia (100%); 5 episodes of mucositis grade III, other Tox: edema: 15 pts (53%) (1 severe); nail changes: 12 pts (42%). Activity 22 pts evaluable (2 early death and 5 too early): 4 PR (6+, 7+, 7+, 8), 11 Minor Response, 7 PD. Median TIP (all pts) 3 months (1–8). Encouraging results and acceptable toxicity in a multitreated cohort confirm the value of TXT and its interest as second or first line treatment in MBC.