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The pharmacological costs of regimens used as front-line therapy in advanced colorectal cancer patients and their impact on the liver resection rates have not been considered. In this paper, we made a review of published randomized Phase II and III trials that reported the liver resection rates following upfront chemotherapy and linked this outcome to the pharmacological costs of drugs used. The costs are calculated based on the price at Pharmacy of our Hospital in Legnago (Italy), and as a measure of activity, we used the number of patients needed to treat to get one complete liver resection. Number needed to treat is highly variable among the different trials according to patient's characteristics, tumor biology and the efficacy of chemotherapy administered. The range of activity is greatly amplified when the costs are compared.

We evaluated the impact of a carboplatin-based doublet in two groups of elderly patients with advanced non-small cell lung cancers (NSCLC).A retrospective analysis of all consecutive elderly patients (≧70 year old) with advanced NSCLC who received a carboplatin-based doublet as front-line therapy at our medical oncology unit was performed.In the study, 57 consecutive elderly patients with advanced NSCLC were included. Carboplatin was combined with vinorelbine in 41 patients (71·9%) and with gemcitabine in 16 patients (28·1%). Overall, a total of 227 cycles were administered to 57 patients - 142 cycles were administered to patients in group 1 and 85 cycles were given to patients in group 2 - median number of administered cycles per patient was 4 (range 1-6). Of the patients, 35 (62%, group 1) were 'young-old' (70-74-year old) and 20 (38%, group 2) were 'old-old' (75-82-year old). Toxicity was mild in both subgroups (grade 3-4 neutropenia in 17·1% of group 1 and in 9·1% of group 2). At the univariate analysis, the median overall survival (OS) was 10·07 months (P = 0·789, 95% CI: 8·49-11·64), 10·1 months in group 1 and 9·8 months in group 2.This evaluation shows the safety and efficacy of a carboplatin-based doublet given as first-line chemotherapy in elderly advanced NSCLC patients. The combination with vinorelbine or gemcitabine is associated with a very good toxicity profile that does not seem to have a detrimental effect on efficacy.

Aims and background More than 50% of patients with advanced non-small cell lung cancer are diagnosed in the elderly. Few prospective clinical data with cisplatin-based chemotherapy are available, and some authors have suggested that a non-platinum single agent should be the preferred form of cure in these patients. The aim of the study was to evaluate the efficacy and safety of first-line chemotherapy based on platinums (carboplatin or cisplatin) plus a third generation compound (vinorelbine or gemcitabine) in elderly patients with advanced non-small cell lung cancer in daily clinical practice. Methods A retrospective analysis of consecutive elderly (≥70 years of age) patients with advanced non-small cell lung cancer treated at our Medical Oncology Unit from February 2005 to September 2011 was performed. Results A total of 249 cycles of chemotherapy was administered to 62 patients (median age, 72 years; range, 70–81) presenting a median Charlson comorbidity index of 1 and a good ECOG PS (0–1, 52 patients; 2, 10 patients). The median number of cycles/patient was 4, and all 62 patients received a platinum-based doublet as first-line chemotherapy: 57 with carboplatin (92%) and 5 with cisplatin (8%). As best response to the treatment, 19 (31%) partial responses and 20 (32%) stable diseases were observed. Median overall survival was 9.8 months. Toxicity was mild; grade III-IV neutropenia was the most frequently observed side effect in 19 administered cycles (8%). Conclusions Advanced non-small cell lung cancer in elderly patients can be safely treated with a platinum-based doublet. Observed toxicity is manageable, and overall survival is in keeping with data from the literature.

Leptin is overexpressed in human breast tumors and is produced by breast cancer cells in response to obesity-related stimuli. The leptin promoter polymorphism Lep-2548G/A can be associated with increased leptin secretion by adipocytes and elevated cancer risk. However, molecular mechanisms underlying the link between Lep-2548G/A and breast cancer have never been addressed. Lep-2548G/A is proximal to a binding site for the transcriptional factor Sp1. Furthermore nucleolin, a transcriptional repressor, can bind Sp1 or its consensus site. Consequently, we focused on the impact of Lep-2548G/A on Sp1- and nucleolin-dependent leptin transcription in breast cancer cells. The Lep-2548G/A was identified in a homozygous conformation in BT-474 and SK-BR-3 breast cancer cells, in a heterozygous conformation in MDA-MB-231 cells, and a wild-type Lep-2548G/G sequence was present in MCF-7 and ZR-75-1 cells. The occurrence of Lep-2548A/A and Lep-2548G/A coincided with high and intermediate leptin mRNA expression, respectively, while cells containing Lep-2548G/G expressed low leptin mRNA levels. We demonstrated that the existence of Lep-2548G/A improved efficient recruitment of Sp1 to DNA under insulin treatment, while Sp1 loading on DNA containing Lep-2548G/G was not insulin-dependent. In contrast, nucleolin binding to Lep-2548G/A was downregulated in response to insulin, while it was not regulated on Lep-2548G/G. The presence of Lep-2548G/A was studied in breast cancer epithelial cells by IHC and LCM. Interestingly, all 14 tumors expressing high leptin levels contained Lep-2548A/A. In conclusion, the occurrence of Lep-2548G/A can enhance leptin expression in breast cancer cells via Sp1- and nucleolin-dependent mechanisms and possibly contribute to intratumoral leptin overexpression. © 2009 UICC

The combination of Taxotere (docetaxel), cisplatin, and prolonged-infusion 5-fluorouracil (5-FU) has emerged as an active treatment for advanced gastric cancer. However, the regimen proposed by van Cutsem et al. (J Clin Oncol 24:4991-7, 2006) is associated with significant toxicity and therefore alternative schedules are needed. In the present study, patients with advanced gastric or esophageal cancer received Taxotere 35 mg/m(2) and cisplatin 25 mg/m(2) on day 1, followed by 5-FU 180 mg/m(2)/day as a 7-day prolonged infusion. Drugs were given weekly for 3 consecutive weeks followed by 1 week's rest. Cycles were repeated every 4 weeks. Overall, a total of 110 cycles were administered to 27 patients (median age 63 years, range 40-78 years). The median number of cycles per patient was 4 (range 2-6). Nine partial responses were obtained, resulting in an overall response rate of 33% [95% confidence interval (CI) 16-51], a median time to progression of 6.4 months (95% CI 5.4-7.4), and a median overall survival of 10.7 months (95% CI 6.6-14.8). Toxicity was mild; grade III-IV neutropenia was the most frequently observed side effect, in 9 administered cycles (8%); neutropenia was complicated by fever in 2 cycles. Other grade III-IV toxicities observed in5% of patients were anemia and mucositis.

This study compares the incidence of local and regional recurrence of breast cancer between two contiguous time windows in a homogeneous population of 137 patients who underwent fat tissue transplant after modified radical mastectomy. Median follow-up time was 7.6 years and the follow-up period was divided into two contiguous time windows, the first starting at the date of the radical mastectomy and ending at the first lipoaspirate grafting session and the second beginning at the time of the first lipoaspirate grafting session and ending at the end of the total follow-up time. Although this study did not employ an independent control group, the incidence of local recurrence of breast cancer was found to be comparable between the two periods and in line with data from similar patient populations enrolled in large multicenter clinical trials and who did not undergo postsurgical fat tissue grafting. Statistical comparison of disease-free survival curves revealed no significant differences in relapse rate between the two patient subgroups before fat grafting and after fat grafting. Although further confirmation is needed from multicenter randomized clinical trials, our results support the hypothesis that autologous lipoaspirate transplant combines striking regenerative properties with no or marginal effects on the probability of post-mastectomy locoregional recurrence of breast cancer.

Background Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates with specific clinicopathological features. Methods Expression of ObR, HER2, phospo-HER2 was assessed by immonoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fisher's exact test for count data. Results HER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors. Conclusion Coexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments.

e17551 Background: The aim of this study is to evaluate the pharmacological costs of conversion chemotherapy in an unselected population of advanced colorectal cancer patients. Methods: Phase III studies evaluating chemotherapy regimens for advanced colorectal cancer patients were considered. The percentage of reported complete liver resection in each arm was used to calculate the number of patients needed to treat (NNT) to get a complete liver resection. This number was multiplied by the number of cycles administered before the resection (assuming 6 cycles for biweekly chemotherapy or 4 cycles for chemotherapy given every three weeks). Calculation is based on an “ideal patient” (BSA 1.8 sqm; weight 70 Kg).The costs of drugs are at the Pharmacy of our hospital and are expressed in €. Results: Results are summarized in the Table. Conclusions: The pharmacological costs to obtain a complete resection of liver metastases from colorectal cancer varies widely across the different chemotherapy regimens commonly used and is influenced by the efficacy of the treatment and by the costs of drugs used. Schemes containing a “biological” are associated with an increased of costs. [Table: see text]

678 Background: The rate of cell proliferation correlates with the response of breast cancer to chemotherapy and disease outcome. The Ki-67 protein is a useful histopathological marker for assessin...

688 Background: The aim of our study was to highlight any time related changes in BC characteristics and surgical management of 3615 pts with early invasive tumours T1-T3 collected from 1992 to 2002 in Verona (Italy). Methods: We considered tumour size (T1, T2, T3), nodal involvement (N0, N1–3, N4–10, N>10), Grading (G1, G2, G3); Ki-67 (0–25%, 26–100%); ER, PgR, p21, p53, c-erbB2, BCL2 (-ve/+ve) and vascular invasion; age at diagnosis ( 50 years), modality of diagnosis (asymptomatic/symptomatic), type of surgery (conservative/radical), axillary dissection, number of examined nodes (N0–10, N>10) and reconstruction. Results: BC diagnosed more recently were smaller (T1: 54.9% in ’92 vs 74.9% in ’02; T2: 41.9% in ’92 vs 22.4% in ’02, p 25%: 11.9% in...

771 Background: Tumour size and node involvement are the most important prognostic factors in breast cancer (BC). Node-negative (N-) and T1 BCs usually have a better prognosis, but some of these patients experience a recurrence and die of systemic disease. Materials and Methods: We studied 1857 patients with invasive N- and T1 BCs to evaluate the importance of the tumour diameter and correlated it with pathological, biological and clinical parameters in order to define a subgroup of patients at higher risk of recurrence. T1a, T1b and T1c tumours were correlated with grading (G1, G2, G3), vascular invasion (VI) (positive vs negative), ER and PgR (positive vs negative), Ki-67 proliferative index (low 0–10%; intermediate 11–25%; high 26–100%), mammary family history (MF) (positive vs negative) and type of diagnosis (asymptomatic vs symptomatic). The data were analysed using the chi-squared test. Results: The larger lesions were associated with poor prognostic factors such as G3 (76.1% in T1c vs 18.1% in T1b ...