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Purpose Given the cumulative neurotoxicity associated with oxaliplatin, a shorter duration of adjuvant therapy, if equally efficacious, would be advantageous for patients and health-care systems. Methods The Three or Six Colon Adjuvant trial is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III colon cancer to receive 3 months or 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin). Primary end-point is relapse-free survival. Results 3,759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX and 36% CAPOX. Two-thirds were stage III. The median time of follow up was 62 months and 772 relapses or deaths have been observed. The hazard ratio (HR) of the 3 months versus 6 months for relapse/death was 1.14 (95% CI, 0.99 to 1.32; P [for noninferiority] = .514) and the CI crossed the noninferiority limit of 1.20. However, the absolute difference in 3-year RFS was 1.9% (95% CI, -0.7% to 4.4%). Counter-intuitively, while the RFS curves were similar for stage III (HR, 1.07; 95% CI, 0.91 to 1.26) and for CAPOX treated patients (HR, 0.98; 95% CI, 0.77 to 1.26), they were not for stage II and for FOLFOX treated patients, with HR of 1.41 (95% CI, 1.05 to 1.89) and 1.23 (95% CI, 1.03 to 1.46), respectively, favoring the 6 months of treatment. Conclusion The Three or Six Colon Adjuvant trial failed to formally show noninferiority of 3 versus 6 months of treatment to the predefined margin of 20% relative increase. The results depended on the adjuvant regimen and risk. For CAPOX, 3 months were as good as 6 months; for FOLFOX, 6 months added extra benefit. Counter-intuitively, the low-risk patients benefitted more than the high-risk population from the 6-month duration. The choice of regimen and duration should depend on patient characteristics and be balanced against the extra toxicity of longer therapy.

5071 Background: There exists considerable biological and clinical variability between histologic variants of metastatic renal-cell carcinoma (mRCC). Data reporting on sites of metastatic involvement in less common histologies of mRCC are sparse. We sought to characterize the frequency of metastatic site involvement across the three most common histologies of mRCC: clear-cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC). Methods: Using the International mRCC Database Consortium (IMDC) database, patients with mRCC starting systemic therapy between 2002-2019 were identified and sites of metastases at the time of systemic therapy initiation were documented. Patients with multiple sites of metastatic involvement were included in analyses of all groups to which they had metastases. The primary outcomes were prevalence of metastatic site involvement and overall survival (OS). Patients with mixed histology were excluded. Results: 10,105 patients were eligible for analysis. Median age at diagnosis was 60, 72% were male and 79% underwent nephrectomy. 92%, 7% and 2% of patients had ccRCC, pRCC, and chrRCC, respectively. Frequency of metastatic site involvement across the histologic subtypes is shown in Table. Lung, adrenal, brain and pancreatic metastases were more frequent in ccRCC, lymph node involvement was most frequent in pRCC, and liver metastases were most frequent in chrRCC. Median OS for ccRCC varied by site of metastatic involvement, ranging between 16 months (brain/pleura) and 50 months (pancreas). OS by site of metastatic involvement was compared between histologies for the four most common sites of metastases (lung, lymph nodes, bone, liver). As compared to patients with ccRCC, patients with pRCC had lower OS regardless of site of metastasis (p < 0.05). Power was limited and thus differences in OS between ccRCC and chrRCC were not detectable. Conclusions: Sites of metastatic involvement differ based on histology in mRCC. These data highlight the clinical and biologic variability between histologic subtypes of mRCC and constitute the largest cohorts of patients with metastatic pRCC and chrRCC to report on sites of metastases. Sites of Metastatic Involvement by Histology. [Table: see text]

4578 Background: While the CARMENA trial prompts more caution with upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC), 17% of patients in the sunitinib alone arm underwent deferred CN (dCN). Upfront systemic therapy has been proposed as a potential litmus test to identify patients suitable for CN, but data on outcomes are limited. We sought to characterize outcomes of dCN after upfront sunitinib relative to sunitinib alone. Methods: Patients with newly diagnosed mRCC receiving upfront sunitinib were identified from the International mRCC Database Consortium (IMDC) from 2006-2018. All CNs done after initial sunitinib were included, excluding CNs performed after sunitinib failure. The outcomes were overall survival (OS) and time to treatment failure (TTF). Kaplan Meier and multivariable Cox regression analyses were performed; dCN was analyzed as a time-varying covariate to account for immortal time bias. Results: The cohort included 708 patients of whom 53 (7.5%) underwent dCN at a median of 6.5 months (IQR 3.5,10.5) from diagnosis. Patients in the dCN group were more likely to have better Karnofsky performance status (KPS), intermediate IMDC risk, fewer metastatic sites, and response to upfront sunitinib (Table). There were 604 deaths during a median follow-up of 63 months. Median OS and TTF with dCN were 43.5 and 19.8 months vs. 9.4 and 4.3 months without, respectively. Upon multivariable analysis, dCN remained significantly associated with OS (HR 0.45, 95%CI 0.31-0.65; p < 0.001) but not TTF (HR 0.73, 95%CI 0.52-1.01; p = 0.056). Conclusions: Patients who received dCN were carefully selected and achieved long OS. With these benchmark outcomes, optimal selection criteria need to be identified and confirmation of the role of dCN in a clinical trial is warranted. [Table: see text]

e21101Background: Several studies have proven the efficacy of maintenance chemotherapy (CT) in advanced NSCLC. The use of low dose (i.e. metronomic) anti-mitotic drugs could exert an anti-angiogeni...

581 Background: There is evidence that cytoreductive nephrectomy (CN) may be beneficial in metastatic renal cell carcinoma (mRCC), but the role of CN in patients with papillary histology is unclear. Methods: Using the IMDC database, a retrospective analysis was performed on patients with papillary mRCC treated with or without CN. Baseline characteristics and IMDC risk factors were collected. Median overall survival (OS) was determined for both patient groups. Multivariable Cox regression analysis was performed to control for imbalances in individual IMDC risk factors. Results: In total, 353 patients with papillary mRCC with (n = 75) or without (n = 278) a component of clear cell histology were identified. Median follow-up time was 57.1 months (95% CI 32.9-77.8) and the OS from the start of first-line targeted therapy for the entire cohort was 13.2 months (95% CI 12.0-16.1). Baseline characteristics are in Table 1 and patients who had CN were more likely to be younger, with better KPS, and have sarcomatoid histology. Median OS in patients with CN was 16.3 months (95% CI 13.1-19.2), compared to 8.6 months (95% CI 6.1-12.2; p < 0.0001) in the no CN group. When adjusted for individual IMDC risk factors, the hazard ratio (HR) of death for CN was 0.62 (95% CI 0.45-0.85; p = 0.0031). Conclusions: The use of CN in patients with mRCC and papillary histology appears to be associated with improved survival when compared to no CN after adjustment for risk criteria. A clinical trial in this rare population may not be possible but this data does corroborate with clear cell literature. [Table: see text]

3501 Background: Six months of oxaliplatin-based treatment has been the standard of care as adjuvant therapy for stage III colon cancer and an accepted option for high-risk stage II. Given the cumulative neurotoxicity associated to oxaliplatin, a shorter duration of therapy, if equally efficacious, would be advantageous for patients and health-care systems. Methods: TOSCA was an open-label, phase III, multicenter, non-inferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months or 6 months of FOLFOX4/XELOX. Primary end-point was relapse-free survival. Results: From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Two thirds were stage III. At the cut-off time for analysis the median time of follow-up was 62 months and 772 relapses or deaths have been observed. The RFS rate at 8 years is 75%. This analysis was done when 82% of the planned number of events was reached, with a power of 72% instead of 80%. The decision to anticipate the analysis was based on the participation to the IDEA joint collaborative analysis of studies sharing this clinical question. The Hazard Ratio of the 3months vs 6 months for relapse/death was 1.14 (95%CI 0.99-1.31, p for non inferiority = 0.253) and the confidence interval crossed the non inferiority limit of 1.20. Conclusions: TOSCA was not able to demonstrate that 3 months of oxaliplatin-based adjuvant treatment is as efficacious as 6 months. Nevertheless , because the absolute difference in RFS between the two treatment durations is small ( less than 3 % at 5 years ), the decision to complete the whole 6-month program should be individualized based on toxicity and patients’ attitude. This study is registered with ClinicalTrials.gov Registration Number: NCT00646607. It was supported by a grant from AIFA (Agenzia Italiana del Farmaco) Grant Code FARM5RWTWZ. Clinical trial information: NCT00646607.

4568 Background: CTCs can be isolated in peripheral blood of cancer pts and have demonstrated to have prognostic role in several metastatic tumors such as breast, colorectal and prostate cancer. Few data are available for Renal Cell Carcinoma-RCC. Methods: We designed a multicenter prospective observational trial aiming to assess the association between CTC counts and PFS of RCC pts treated with an antiangiogenic tyrosine-kinase inhibitors as a first-line regimen for metastatic disease. OS and response rate were secondary objectives. Both basal and sequential counts were enumerated by Cellsearch system at 4 time points: day 0 of treatment, +1 mo, +3 mo, at progression or 12 mo in the absence of progression. Ethics Committee approval was obtained. Results: Among 246 pts, 195 are eligible for the present analysis, 71.4% males, median age 69 yrs (range, 27 to 91), 81% with previous partial/total nephrectomy. Treatment was sunitinib (77.5%), pazopanib (21%) or sorafenib (1.5%). According to Heng criteria there were 24.6% good, 62.6% intermediate and 24.6% poor prognosis pts. After a median follow-up of 31.5 mo, median PFS is 13.6 mo (23% censored), 49.2% of pts are still alive. Investigator-assessed best response was 3.8% complete, 37.3% partial response, 33% stable, 25.9% progression. At baseline 91 pts had 1 or more CTCs, median 2, range 1 to 263. Pts with at least 1 CTC had a significantly shorter PFS compared to negative pts (8.8 vs 16.6 mo, p = 0.03), HR = 1.41 (95%CI 1.02-1.9). Thirty pts had > = 3 CTCs, with a median PFS of 5.8 vs 15 mo in the remaining pts (p = 0.002), HR = 1.99 (CI 1.28-3.03). Percentage of pts with > = 3 CTCs increased from 6.6% of good, 18.4% intermediate and 38.9% poor Heng score pts (p = 0.042). Pts with > = 3 CTCs had a shorter estimated OS of 13.8 mo vs 52.8 mo (p = 0.003), HR = 1.99 (CI 1,17-3.2). Correlation between CTC positivity and response rate was not significant. Conclusions: In this robust multicenter prospective cohort of first-line metastatic RCC pts, the presence of 3 or more CTCs predicts a significantly shorter PFS and OS. Further analyses are ongoing on apoptotic markers of CTCs and concomitant counts of endothelial cells collected in the same cohort.

498 Background: Fourthline targeted therapy efficacy in mRCC is not well characterized and is not reimbursed in many jurisdictions worldwide. Methods: The IMDC consists of consecutive patient series from 35 international cancer centers. It was queried for mRCC patients who received fourth line targeted therapy. Kaplan Meier estimates were used for time to treatment failure (TTF) and overall survival (OS). Results: 594 out of 7498 (8%) mRCC patients initially treated with first line targeted therapy eventually received fourth line therapy from a class of approved agents. Baseline characteristics are displayed in Table 1. The most common fourth line therapies were everolimus 17%, sorafenib 15%, axitinib 13%, pazopanib 13%, sunitinib 13%, nivolumab 7%. IMDC prognostic group distributions (Heng et al JCO 2009) and their associated survivals (both determined from fourth line therapy initiation) were 5% favorable risk (OS 23.1 (14.7-not reached)), 66% intermediate risk (OS 13.8 (11.4-17.5)), and 29% poor risk (OS 7.8 (4.93-12.2)) (OS p

4554Background: Metastatic papRCC is the second most prevalent type of renal cell carcinoma, next to clear cell RCC (ccRCC). Outcome on therapy in metastatic papRCC remains poorly characterized in ...

549 Background: T and N stage, Fuhrman grade, necrosis and sarcomatoid features in the primary tumor are key prognostic factors for relapse of ccRCC, but they are not part of Heng's algorithm applied to predict OS in the metastatic setting, which instead is based on 6 clinical/laboratory items. Methods: Retrospective analysis on correlation between pathological parameters and OS (from start of first-line targeted therapy) and Heng's prognostic factors in a multicenter cohort of pts with advanced ccRCC, all of whom had undergone surgery on the kidney. Results: From 2006 to 2012, data of 903 eligible metastatic pts were collected from 33 Italian Oncology Institutions, median age 66 years, 72.6% males, 36.4 metastatic at diagnosis. After a median observation of 42 mo, 70,5% of pts died, estimated OS is 28.5 mo. Heng good prognosis pts were 14.45%, intermediate 69.1% and poor 16.45%. Univariate analysis showed that all pathological parameters significantly correlated with OS: T stage 3-4 vs 1-2 (HR 1.3), N1 vs N0 (1.3), Fuhrman grade 3-4 vs 1-2 (1.7) presence of necrosis (1.5) and sarcomatoid features (1,6). All pathological parameters had a strong correlation with a time to metastases < 1 year, while only weak correlations were found with the other clinical prognostic items of Heng's model. At multivariate analysis only N stage showed an independent impact on OS (table). Conclusions: T3-4 stage, N1, Fuhrman grade 3-4, presence of necrosis and sarcomatoid features negatively affect OS of metastatic ccRCC, but clinical items of Heng's model confirm to have a more robust prognostic significance at multivariate analysis. [Table: see text]

e13514 Background: Endoxifen (EN), the main active metabolite of tamoxifen (T), reaches steady state (SS) plasma levels after about 4 months of administration. It derives principally by cytochrome CYP2D6 activity, which is highly variable among patients. In order to predict individual SS EN exposure, three different approaches were investigated. Methods: Before starting T administration, 73 breast cancer patients (median age: 59 yrs, range: 30-89) were characterized by means of: 1) a phenotyping test of CYP2D6 activity, based on the urinary metabolic ratio of dextromethorphan/dextrorphan (log transformed, LMR). 2) CYP2D6 genotyping (alleles *1, *3, *4, *5, *6, *9, *10, *41), to classify patients in 3 functional groups: Extensive (EM), Intermediate (IM) and Poor (PM) Metabolizers. After starting T treatment (20mg/day), EN plasma levels were measured after 1 month (1M EN, pre- steady state) and 4 months of therapy (SS EN). ANOVA, paired and unpaired T test and linear regressions were performed to analyze associations between LMR, CYP2D6 genotype, 1M EN and SS EN. Multivariate linear regression was used to create a predictive equation; its mean prediction and absolute errors (MPE% and MAE%) and the positive and negative predictive values (PPV% and NPV%, according to median SS EN) were calculated. Results: SS EN plasma levels varied between 2.4 and 39.2 (median: 8.7) ng/ml. LMR (median: -1.6; range: -3.1- +1.2) showed a significant linear correlation with SS EN (r=-0.59; p

9554 Background: Comprehensive Geriatric Assessment (CGA) may help to evaluate the functional status of elderly patients, but, because time-consuming, RST have been proposed. However, whether these instruments may predict survival is still unclear. The aim of this study was to correlate overall survival (OS) with the results of 3 rapid tests: G8 (1), VES-13 (2, aCGA (3) in patients over 70. Methods: From April 2009 to April 2012, 530 unelected outpatients over 70, 263 males and 267 females, were evaluated. During the first oncologic visit, they were homogeneously assessed by a trained oncogeriatric team using a dedicated, expressly developed web-based software (www: oncoger.ro.it) including all of the 3 rapid tests. Survival curves were drawn using Kaplan-Meier method and compared with log rank test; multivariate analysis was performed according to Cox regression method. Results: The tests identified frail patients as follows: VES-13 69%, aCGA 50%, G8 68.5%. Frailty was significantly associated with poor OS, with different hazard ratios (HR) for each test. HRs for death of frail vs non-frail pts were for aCGA 1.45 (95%CI 1.09-1.89, p=0.008), for VES-13 1.55 (95%CI 1.12-2.00, p=0.005) and for G8 2.57 (95%CI 1.66-2.93, p

e20541 Background: Pharmacogenetic tests (PGT) are intended to predict the efficacy and toxicity of a specific treatment. There is a common concern that they may be misunderstood by patients (pts), confused with predictive tests for hereditary disorders and induce psychological distress. Methods: As part of a study aimed at correlating individual T activation capability with disease recurrence, CYP2D6 genotyping was offered to 203 early breast cancer pts. On enrolment, they received complete verbal and written information by their oncologist about the test and its purpose. Six months later they were asked to answer 4 questions concerning the nature and the possible psychogenic stress aroused by PGT. Their level of anxiety was assessed by the Zung-Self-Rating anxiety scale. Results: Anxiety was absent in 39%, within the normal limits in 50% or mild in 9% of pts. Only two pts had a moderate score. Anxiety was not associate with age or time from cancer diagnosis. Although not significantly, its score was higher in pts with larger tumors and positive lymph nodes. All pts agreed on the usefulness of PGT to enable the prediction of differences in drug response and toxicity. Some of them believed that they could predict some disease risks: the misperception was higher among elderly pts (> 70y, 50%) while was infrequent in younger pts (70 years old, respectively. Conclusions: CYP2D6 genotyping to predict tamoxifen activation was welcomed, well understood and was not associated with anxiety in the majority of breast cancer pts on adjuvant treatment. It seems that, when properly informed by their physician, patients show a positive attitude towards PG testing and no psychological distress. Funded by Regione Veneto. Clinical trial information: 532.

e15512 Background: Several prognostic factors in mRCC have been largely described in the literature. This study was aimed to verify whether some of these factors maintain their prognostic role in a cohort of pts treated in the community setting outside clinical trials. Methods: 902 pts with mRCC treated with TT from 2007 to December 2012 in 28 Italian centres were included in the analysis. Various potential prognostic factors were correlated with overall survival (OS). Results: Median age was 60 (range 25-89), 75% of pts were males; median OS (mOS) was 24 mo. Histology was clear cell (CC), CC with sarcomatoid component, papillary, NOS, not available in 82%, 6%, 4%, 4% and 4 %, respectively. mOS in the CC subgroup was 28 vs 12.5 mo of the non CC subset (p2 in 43% of the pts. mOS of this group was 18 mo vs 31 mo of pts with ≤2 metastatic sites (p=0.0001). MSKCC risk was good in 32%, intermediate in 53% and poor in 15% of the pts. According to MSKCC risk score, mOS was 6.4, 24 and 49 mo in poor, intermediate and good subsets, respectively (p

e13019 Background: TAM is mainly metabolized by CYP2D6 to form its most active metabolites, 4hydroxy-tamoxifen (4OH-T) and endoxifen (END). Because of its long half-life, steady state is reached after around 4 months of continuous intake. The wide variable inter-patient activity of CYP2D6 might influence drug efficacy. A multi-institutional study in north Italy is evaluating the relationship between END levels and outcome. As a part of it, we investigated the role of dextromethorphan (DM), a probe drug for CYP2D6 enzymatic activity, as a potential phenotyping test for TAM activation. Methods: Twenty-nine breast cancer patients (75% postmenopausal) on adjuvant TAM therapy (20 mg/die) were investigated. They received a single dose (15 mg) of oral DM before starting TAM and their urines were collected over the10 following hours. Simultaneous quantitative determination of DM and its metabolite dextrorphan (DO) was performed in urines to estimate their log transformed metabolic ratio (LMR=logDM/DO). After 4 months a blood sample was collected to characterize TAM exposure at steady state; plasma levels of TAM, END, 4OH-T and the non active END precursor N-desmethyltamoxifen (NDT) were quantified by HPLC. Linear regression analysis and t test were performed for correlating LMR and drug plasma levels. Results: LMR varied between -2.15 and 0.90 (median: -1.37) while steady state plasma levels of END varied between 1.9 and 15.0 ng/ml (median: 4.36) and 4OH-T between 0.9 to 3.1 ng/ml (median:1.72). A significant correlation (r = 0.56; p= 0.0013) was found between LMR and END plasma concentrations. The patients with high LMR (> median value), compared to patients with low LMR, had lower END (3.7 vs 7.5 ng/ml, p=0.0003), lower 4OH-T (1.6 vs 2.1 ng/ml, p=0.04) and, accordingly, higher NDT (291.2 vs 198.2 ng/ml, p=0.025). Conclusions: DM/DO urine ratio obtained before starting therapy correlates with TAM biotransformation activity and can predict steady state active metabolites exposure in individual patients. This phenotyping test is fast, simple and unexpensive and could contribute to the personalization of adjuvant breast cancer treatment. Funded by Regione Veneto.

9155 Background: The use of chemotherapy in vulnerable and frail elderly pts still represents a challenge in geriatric oncology. PLD represents an appealing drug in elderly pts, because of reduced ...

e14571 Background: The aim of the study was to evaluate if genetic polymorphism of DNA repair genes may predict pathological response and survival in patients affected by locally advanced esophageal cancer, treated with a neoadjuvant schedule including weekly DTX (35 mg/mq) and CDDP (25mg/mq), protracted venous infusion of FU (150 mg/mq/die) and concomitant radiotherapy for 8 weeks followed by surgery. Methods: Fifty-seven patients were enrolled, aged 60±7 years old. Median follow-up was 27 months. Genomic DNA was extracted from peripheral blood lymphocytes and XPA, XPD, XRCC1, ERCC1 and XRCC3 were genotyped through RFLP analysis. Associations between gene polymorphisms and pathological response and survival were analysed through Chi square test and Log rank test respectively. Results: Thirty-two patients presented complete remission (pCR) and 10 patients microfocal residual disease (pMRD); the remaining 15 patients were considered stable or non-responders (pS-NR). The event free(EFS) and overall (OS) median survival times have not yet reached; significantly better 3-year survival rates were observed after pCR than in case of pMRD and pS-NR (EFS: 87% vs 42.8%, p=0.0004; OS: 86% vs 56%, p=0.02, respectively). No association was found between pathological response or survival with XRCC1, ERCC1 and XPD polymorphisms. On the contrary, the XPA 23AA genotype showed an increased risk of recurrence (HR=3.5; 95% CI 1.3 to 43.7, p=0.02) and death (HR=4.4, 95% CI 1.9 to 78.2, p=0.009); there was a trend for reduced risk of negative pathological response with decreasing number of allele 23A : MRD and S-NR were found in 71%, 45% and 35% cases for AA, AG and GG genotypes, respectively. The XRCC3 241MetMet variant was significantly associated with increased risk of death (HR= 6.0, 95% CI 3.0 to 40.0, p=0.008); a trend toward a higher recurrence (p=0.07) and worse response (60% vs 43%) was found. Conclusions: XPA and XRCC3 gene defective variants were significantly associated with worse outcome and could predict OS in esophageal cancer patients treated with a neo-adjuvant intensive radio-chemotherapy protocol. Founded by CARIPARO, Italy No significant financial relationships to disclose.

4548 Background: The achievement of pathological complete response (pCR) seems essential to improve survival in EC. In a phase I study (Pasini et al, Ann Oncol 2005) we demonstrated the feasibility of a novel protocol of neoadjuvant chemoradiation. Based on these promising results, we have performed a phase II study. The primary end point was the pathological response rate, the secondary end points were survival and toxicity. Methods: 74 pts with stage II-III EC (37 adenocarcinomas) were enrolled; median age was 59 yrs (42–73). Treatment consisted of D 35 mg/m2 and P 25 mg/m2 d 1,8,15,29,36,43,50,57 plus 5-FU 180 mg/m2 c.i. d 1–21 and 150 mg/m2 c.i. d 29–64; concurrent RT (50 Gy) started on d 29. Surgery was performed 6 to 8 weeks after completion of RT. Results: 65/74 pts (88%) completed the planned chemo-radiation, while 9 required dose modification of chemotherapy. Median follow-up of living pts was 40 mo (18–75). Pathological findings: pT0 pN0 (pCR): 35 (47%); pTrm pN0:11 (15%)[residual microfoci]; Others: 28 (38%). The overall median survival was 50 mo; median survival times of Others, pTrm, and pCR subsets were 17, 42 months and not reached, respectively (p [Table: see text] No significant financial relationships to disclose.

12005 Background: Doxorubicin formulated in polyethylene-glycol coated liposomes (PLDox) have a prolonged circulation time and a different toxicity profile compared with the free drug; it has been demonstrated that its pharmacokinetics correlate with toxicity, when administrated at standard doses and schedules in young patients. To further decrease side effect risk in elderly breast cancer patients a PLD schedule have been proposed with reduced doses (20 mg/m2) and dose intensity maintained by shortening time between administrations (15 days).The aim of our ongoing study is to monitor doxorubicin plasma levels during the first two cycles and to evaluate if this procedure can help treatment design. Methods: Five women have been enrolled, aged between 74 and 78 years, affected by liver or bone metastasis by breast cancer, previously treated with anticancer drugs and refractory to hormone therapy. Blood samples were obtained 10 minutes, 1 hour, 24 hour, 72–96 hours, 7 and 14 days after the end of one-hour dr...

20659 Background: Recent data suggest that rHu-G-CSF administered 24–48 hours before the expected nadir is likely to be as effective as standard schedules. This study was aimed at evaluating if per...

6560 Background: limited data exist whether, in the long-term, the PCR for the rearranged immunoglobulin heavy chain region may define groups with different prognosis. Methods: 113 pts from the sam...

4059 Background: dose-dense therapy should allow more frequent delivery of moderate doses over a short period with greater efficacy and lower toxicity than standard doses every 3 weeks. This neodjuvant phase I protocol was based on weekly D and cisplatin (P), continuous infusion (c.i.) of 5-FU and concomitant RT. The doses of D and RT were progressively escalated. Aims were pathological response rate and toxicity. Methods: from Oct 99 to Oct 03, 41 non metastatic pts (31 adenocarcinomas) were enrolled; median age was 61 yrs (47–76). Step 1: D and P 20 mg/m2 d 1,8,15 plus 5-FU 150 mg/m2 c.i. d 1–21. After one week rest, the same cycle was repeated at days 28, 35, 42 concurrently with RT (40 Gy). Step 2: D and P 25 mg/m2; 5-FU 180 mg/m2 days 1–21. Step 3: 5-FU prolonged to four weeks during RT (150 mg/m2 days 28–56). Step 4: D and P 25 mg/m2 added at day 49. Step 5: RT increased to 50 Gy. Step 6: D 30 mg/m2. Step 7: D 35 and P 25 mg/m2 added at day 56 and 5-FU prolonged to 5 weeks. Surgery was performed 4 t...