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17532 Background: Gold standard treatment of CD20+ aggressive B-cell non-Hodgkin lymphoma, R-CHOP, has been suggested to improve outcome when administered as dose-dense regimen supported with G-CSF. The non-pegylated liposomal doxorubicin (Myocet) has an improved safety profile compared to standard formulations of doxorubicin. Standard R-CHOP regimen has been modified replacing doxorubicin with Myocet, administered on a biweekly basis (R-COMP-14) looking for an increase in efficacy without impairing tolerability Methods: Single arm, multicentric, 2-step (Simon design) phase II trial. Newly diagnosed, diffuse large B-cell lymphoma, stages III, IV or I, II with IPI ≥ 1, CD20+, eligible patients (Pt) were treated with Myocet 50 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2 (max. 2 mg), rituximab 375 mg/m2 and prednisone 100 mg/d d1–5 in biweekly cycles. Pegilated filgastrim (Neulasta™) was administered on day 2 of the cycle. Response was assessed after 3 cycles, and patients with PR or CR received 5 additional cycles. A safety analysis was planned by protocol with data of first patients included Results: The median age of the 13 Pt included was 59 (range 28–64). At baseline 53.9% Pt had III-IV stage and 41.7% had extraganglionar involvement. Median basal LVEF was 66% (range 44–79). A median of 7 cycles of R-COMP were administered. The median relative dose intensity per week for Myocet was 94.9%. 6.2% of the cycles were delayed and 8.6% of the cycles were dose reduced. There were 2 episodes of febrile neutropenia. G3 asthenia, G3 neurotoxicity and G3 related infection were found in one cycle each. One patient had G3 hepatic toxicity resolved with dose reduction. At the end of treatment the median LVEF was 65.52% (range 52–76), there was no cardiac event related to the treatment. 84.6% of Pt had complete or partial response (7 RC, 2 uRC, 2 PR, 1 SD, 1 PD) at the end of the study Conclusions: In this small safety group of Pt that received the dose-dense regimen, the preliminary results suggest that R-COMP-14 supported with Neulasta is a well tolerated and effective regimen. Recruitment will proceed as planned (75 Pt). No significant financial relationships to disclose.

7592 Background: Several studies have shown that the addition of rituximab (R) to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisona), or shortening the interval between cycles of chemotherapy to two weeks, improves survival of patients with DLBCL. These studies prompted our group (GOTEL) to evaluate in a prospective study, the feasibility and efficacy of R-CHOP-14 in patients (pts) with DLBCL. Methods: Patients (younger than 70 years) with stage II bulky, III or IV DLBCL, and no significant co-morbidities were included in the study. R was administered on day 1 before chemotherapy. R-CHOP was recycled every 14 days. No antimicrobial prophylaxis was administered. All pts received filgrastim (5 μg/kg) from day +3 to +10. Pts received 6 cycles if CR was achieved after 3 cycles; those in PR, and those pts with bone marrow disease at diagnosis, received 8 cycles. Involved field radiation therapy was permitted for pts with stage II bulky disease. Results: From May 2002 to august 2004, 77 pts were included. Median age was 54 years (range, 15–70); 55 patients were younger than 60 years. According to the age adjusted International Prognostic Index (aaIPI), 13 pts (17%) had low risk disease, 27 pts (35%) low-intermediate risk, 29 pts (38%) high-intermediate risk, and 8 pts (10%) high risk disease. Grade 3–4 toxicity occurred as follow: neutropenia in 15 pts (19%), anaemia in 7 pts (9%), thrombocytopenia in 4 pts (5%), mucositis in 4 pts (5%) and peripheral neurotoxicity in 4 pts (5%). Ten pts were hospitalized (febrile neutropenia: 8 cases, one case of gastric perforation and one pulmonary embolism). After therapy, 61 pts (79%) achieved a CR/CRu (C.I. 95%: 57%-90%) and 14 pts (18%) a PR. 2 pts (3%) had refractory disease. With a median follow-up of 20 months, progression-free and overall survival at 24 months were 68% and 87%, respectively. Conclusions: Administration of R-CHOP-14 (with filgrastim support) is feasible and effective in patients younger than 70 years. [Table: see text]

Introduction: Adjuvant therapies have prolonged survival of non-metastatic breast cancer (NMBC) patients, but they also decrease bone mineral density (BMD). There is and increased interest in the potencial rol of bisphosphonate drugs in preventing and treating chemotherapy-induced bone loss. Objective: We have analyzed the effects of chemotherapy on BMD of women with NMBC who received before first cycle intravenous zoledronic acid. Patients and methods: We prospectively included 55 women with NMBC (stage I–III) referred to the Medical Oncology Service of University Hospital of Canary Islands between September 2003 and August 2005 (53.4 T 12 years; 38.2% premenopausal). We measured lumbar and hip BMD (g/cm) at diagnosis and after twelve months of the first cycle. Before chemotherapy all patients received an intravenous bisphosphonate (zoledronic acid). Results: BMD after 12 months (n = 55) significantly increased in femoral neck (0.797 T 0; 0.822 T 0, P = 0.002) areas, and remained stable lumbar, trochanter, total hip, intertrochanter, and Wards triangle areas.

Purpose. The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC). Patients and Methods. Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety. Results. The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0–53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand–foot syndrome, and neuropathy. Conclusion. Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with single-agent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients.

Abstract 3660 Poster Board III-596 Introduction Despite the major advances in the treatment of classical Hodgkin Lymphoma (cHL) patients, around 30% to 40% of cases in advanced stages may relapse or die as result of the disease. Current predictive systems, based on clinical and analytical parameters, fail to identify accurately this significant fraction of patients with short failure-free survival (FFS). Transcriptional analysis has identified genes and pathways associated with clinical failure, but the biological relevance and clinical applicability of these data await further development. Robust molecular techniques for the identification of biological processes associated with treatment response are necessary for developing new predictive tools. Patients and Methods We used a multistep approach to design a quantitative RT-PCR-based assay to be applied to routine formalin-fixed, paraffin-embedded samples (FFPEs), integrating genes known to be expressed either by the tumor cells and their reactive microenvironment, and related with clinical response to adriamycin-based chemotherapy. First, analysis of 29 patient samples allowed the identification of gene expression signatures related to treatment response and outcome and the design of an initial RT-PCR assay tested in 52 patient samples. This initial model included 60 genes from pathways related to cHL outcome that had been previously identified using Gene Set Enrichment Analysis (GSEA). Second, we selected the best candidate genes from the initial assay based on amplification efficiency, biological significance and treatment response correlation to set up a novel assay of 30 genes that was applied to a large series of 282 samples that were randomly split and assigned to either estimation (194) or validation series (88). The results of this assay were used to design an algorithm, based on the expression levels of the best predictive genes grouped in pathways, and a molecular risk score was calculated for each tumor sample. Results Adequate RT-PCR profiles were obtained in 264 of 282 (93,6%) cases. Normalized expression levels (DCt) of individual genes vary considerably among samples. The strongest predictor genes were selected and included in a multivariate 10-gene model integrating four gene expression pathway signatures, termed CellCycle, Apoptosis, NF-KB and Monocyte, which are able to predict treatment response with an overall accuracy of 68.5% and 73.4% in the estimation and validation sets, respectively. Patients were stratified by their molecular risk score and predicted probabilities identified two distinct risk groups associated with clinical outcome in the estimation (5-year FFS probabilities 75.6% vs. 45.9%, log rank statistic p≈0.000) and validation sets (5-year FFS probabilities 71.4% vs. 43.5%, log rank statistic p Conclusions We have developed a molecular risk algorithm that includes genes expressed by tumoral cells and their reactive microenvironment. This makes it possible to classify advanced cHL patients with different risk of treatment failure using a method that could be applied to routinely prepared tumor blocks. These results could pave the way for more individualized and risk-adapted treatment strategies of cHL patients, enabling subsets of patients to be identified who might benefit from alternative approaches Disclosures: No relevant conflicts of interest to declare.