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7540 Background and Objectives: Angiogenesis is essential for tumor growth & metastasis. It is controlled by angiogenic factors, one of the most important being vascular endothelial growth factor (...

3690 Background: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially in colorectal cancer (CRC). Blocking EGFR activation represents an innovative strategy...

3003 Background: Significant activity of AG-013736, an oral small molecule with potent inhibitory effects against the VEGF receptors 1 (VEGFR-1) and 2 (VEGFR-2) and PDGF receptor, is reported in a ...

4653 Background: MUC1 is a glycoprotein located at the apical surface of glandular epithelial cells. In some tumors, MUC1 is often aberrantly over-expressed and hypoglycosylated, unmasking new antigenic epitopes. This makes it a potential target for tumor-specific vaccination. In renal cell carcinoma (RCC), MUC1 expression is associated with a poor prognosis. TG4010 is a cancer vaccine based on a modified vaccinia virus (MVA) expressing both MUC1 and Interleukin 2. The phase II study objective was to determine the overall response rate of TG4010 alone and in combination with cytokines in a two-step design. Methods: Patients (pts) with progressive metastatic RCC, expressing MUC1 in at least 50% of the tumour cells, received subcutaneous injections of TG4010 weekly for 6 weeks then every 3 weeks until progression, then the TG4010 was combined with Interferon alpha-2a (INF) and Interleukin 2 (IL2). Response to treatment was evaluated every 12 weeks according to the RECIST criteria. Median time to progression...

7541 Background: Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) play an essential role in tumor angiogenesis and are closely related with malignancies. However, the prognostic...

7090 Background: We previously reported the preliminary activity and tolerability of the combination of the EGFR tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) and docetaxel in patients wit...

7551 Background and aims: Circulating vascular endothelial growth factor (VEGF), soluble EGFR and soluble interleukin-6 (IL-6) are associated with metastatic malignant melanoma disease. However, their relationship remains unclear. The aims of this study is to correlate serum IL-6 to sVEGF-A, or EGFR levels and to investigate the clinical significance of these parameters on the overall survival in metastatic malignant melanoma. Methods and Patients: using a sensitive enzyme-linked immunosorbent assays, VEGF-A, EGFR and IL-6 were measured in sera of 64 patients with a fully documented history of metastatic malignant melanoma patients in comparison with 30 healthy controls. Results: serum levels of VEGF-A, EGFR, and IL-6 were significantly increased in melanoma patients compared with healthy controls (p

5015 Background: EGFR expression is increased in 35–70% of primary OC, and often correlates with poor prognosis. Gefitinib (Iressa, ZD1839) is an orally active EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor). Methods: Multicenter, open, non-comparative study in pts with platinum-resistant (relapsed 6 months) OC, with measurable disease, or non-measurable disease with rising CA125, and after only one line-therapy with cisplatin or C, and P. Pts received gefitinib (500 mg/day), P (175 mg/m2), and C (AUC=5) every 3 weeks, for 6–8 cycles. After which, pts could continue to receive gefitinib. Response was assessed by RECIST or Rustin criteria. Results: Since April 2002, 41 pts (median age: 58 yrs (range 34–71)) and an ECOG performance status (0/1/2) of 27/14/0, were enrolled. In 40 assessed pts, 7 were non-evaluable for efficacy (early withdrawal (1), toxicity (2), no target lesions (4)). The overall response rates (CR and PR) were 25% and 71% i...

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...

7531 Background: high blood levels of vascular endothelial growth factor (VEGF) appear to be associated with a poor prognosis in advanced cancer, probably as a consequence of its angiogenic and immunosuppressive effects. The prognostic significance of serum VEGF levels and its variation during cancer treatment is still unknown. Objectives: The aim of this study is to evaluate the clinical usefulness of active serum vascular endothelial growth factor (sVEGF-A) levels in metastatic malignant melanoma patients and to investigate the possible relationship between sVEGF-A variations and clinical response during biochemotherapy. Patients and Treatment: The study included 73 patients with a fully documented history of metastatic malignant melanoma. Biochemotherapy consisted of Cisplatinum, rIL-2 and Alpha-interferon in two induction cycles. The assessment of clinical response was performed according to WHO criteria. Sixty seven patients were evaluable: 43 % (29/67) were responding (RC&RP) and 57 % were non-respo...

CPT-11, a DNA topoisomerase I inhibitor has been confirmed to demonstrate an anti-tumor effect specially against colorectal cancer (CRC). In order to define the best schedule combining the most two active agents in CRC, we initiated in June 94 a phase I study at the starting dose (level 1) of C 200 mg/m 2 (over 30 minutes) and F (500 mg/m 2 on day 1 to 5 by IV bolus administration). To find a sequence-dependent toxicity, C was given at day 0 on cycle 1 (CF) and at day 6 on cycle 2 (FC), then the better tolerated cycle was continued. Escalation schedule initially projected for C was 200, 230, 260, 300, 350, 400, 450 and 500 mg/m 2 . A death occurred at the level 1 (fatal dyspnea in a patient with a bulky mediastinal involvement), probably not related to the treatment, but we decided to reduce 5FU to 375 mg/m 2 /day. Characteristics of the 16 patients entered in the study are following: median age: 57 years (range: 40–70), sex: 12 males, 4 females, PS: 0: 9, 1: 7; all patients had solid tumors refractory to previous treatment (colorectal: 12, oesophagus: 2, lung: 1, pancreas: 1). Level CPT-11/5FU No. pts No. Cycles Diarrhea gr.III/IV Neutropenia gr III/IV 1 200/500 2 2 1/0 1/1 2 200/375 8 34 3/1 0/0 3 230/375 6 12/0 0/0 3/0 5 hospitalizations (1 at level 3) occurred (2 for IV fluid administration) and alopecia was reported in 1 patient (level 3). Further escalation is warranted to determine the maximal tolerated dose. A pharmacodynamic study is underway to investigate potential interactions between C, F and SN38 according to the schedule administrations.

Background The combination of everolimus and the imidazoquinoline derivative, BEZ235 (dactolisib), a dual PI3K/mTOR inhibitor, demonstrated synergy in a preclinical model. Objective To establish clinical feasibility, a phase Ib dose-escalation trial investigating safety and pharmacokinetics of this combination in patients with advanced tumors was performed. Patients and Methods BEZ235 was orally administered daily in escalating doses of 200, 400, and 800 mg along with everolimus at 2.5 mg daily in 28-day cycles. Nineteen patients were enrolled. Adverse events and tumor responses were evaluated using CTCAE v4.0 and RECIST 1.1, respectively. Pharmacokinetic analyses were performed. Results Common toxicities observed included fatigue, diarrhea, nausea, mucositis, and elevated liver enzymes. No confirmed responses were observed. BEZ235 pharmacokinetics exhibited dose-proportional increases in Cmax and AUC0-24 over the three doses, with high inter-individual variability. Non-compartmental and population pharmacokinetic-based simulations indicated significant increases in everolimus Cmax and AUC0-24 on day 28 and decreased clearance to 13.41 L/hr. Conclusions The combination of BEZ235 and everolimus demonstrated limited efficacy and tolerance. BEZ235 systemic exposure increased in a dose-proportional manner while oral bioavailability was quite low, which may be related to gastrointestinal-specific toxicity. The changes in steady-state pharmacokinetics of everolimus with BEZ235 highlight potential drug–drug interactions when these two drugs are administered together. Clinicaltrials.gov: NCT01508104 Electronic supplementary material The online version of this article (doi:10.1007/s11523-017-0482-9) contains supplementary material, which is available to authorized users.

4509 Background: Clear cell renal carcinoma (RCC) is characterized by inactivation of the von Hippel-Lindau tumor suppressor gene, which leads to overexpression of hypoxia-regulated genes including...

8603 Background: Patients with abnormal renal function are at high-risk for drug-induced nephrotoxicity. Furthermore, near half anticancer drugs are predominantly excreted in urine and dosage adjustment in RI is therefore a crucial issue. In 2005, the IRMA study (Insuffisance Rénale et Médicaments Anticancéreux) thus investigated the prevalence of RI in cancer patients and the profile of anticancer drugs prescribed. Methods: Data were collected for cancer patients presenting at one of the 14 IRMA centers in February 1st-15th or October 1st-15th, 2004: type of tumour, sex, age, weight, serum creatinine (SCR), haemoglobinemia, anticancer drugs. Dialysis and myeloma patients were not included. The prevalence of SCR>110 μmol/L was assessed. GFR was estimated with the Cockcroft-Gault (CG) and the abbreviated MDRD (aMDRD) formulae and patients were classified according to their K/DOQI stage of RI (Table). Anticancer drugs necessitating dosage adjustment and those potentially nephrotoxic were identified. Results: 4,684 patients (Breast, 1,898; Colorectal, 573; Lung, 445; Ovarian, 270; Prostate, 222) were included: mean age 58.1 years, weight 65.8 kg, sex-ratio 0.55. The prevalence of elevated SCR was 7.2% and those of GFR [Table: see text] No significant financial relationships to disclose.