Background: The cancer treatments often bring with it body image challenges, causing low self-esteem and contributing to worsen the quality of life (QoL). Chemotherapy (CT)-induced hair loss (HL) is one of the most emotionally distressing side effects of several breast cancer (BC) treatments. The DigniCap system (DCS), using the scalp cooling system, has been shown to reduce CT-induced alopecia (A) in a multicenter prospective trial. The purpose of this prospective observational study was to describe our experience. Materials (patients) and methods: From February 2016 and April 2017, 40 consecutive early stage BC pts who received anthracycline and/or taxane-based treatment were enrolled, post local Ethics Committees approval. A nurse and a psychologist were dedicated for these pts. A/HL has been graduated according to the Dean's scale: G0= no HL; G1 < 25% HL; G2=25–50% HL; G3=50–75% HL; G4 >75% HL. Results: A total of 40 women were enrolled; median age was 49 years (range 31-64). Seventeen pts (42.5%) received 4 courses of EC (epirubicin at 90 mg/m2 and cyclophosphamide at 600 mg/m2 intravenously on day 1, with 21 days between cycles) followed by 12 courses of Paclitaxel 80 mg/m2 intravenously once a week); 21 (52.5%) received 4 courses of EC and 2 pts (5%) Paclitaxel (P 80 mg/m2 intravenously once a week) and concurrent Trastuzumab (2 mg/Kg intravenously; loading dose 4 mg/kg) for 12 consecutive doses. Full preservation of the hair (G0) was observed in 6 pts (15%), G1 in 15 pts (37.5%) and G2 in 7 pts (17.5%) (Table 1). Twenty-eight pts (G0-2=70%) did not need a wig or other hair piece to mask their hair loss during the chemotherapy period; only 6 pts (15%) used wig or head cover.The majority of pts tolerate DCS very well. Among G3 DCS-related side effects, coldness (n = 11, 27.5%), neck pain (n = 4, 10%) and headache (n = 3, 7.5%) were the main toxicity.Overall, 4% (n = 4) of pts discontinued DCS because of unsatisfactory hair preservation (n = 3; 7.5%) and cold discomfort (n1; 2.5%).Table: C57A/HL according to the Dean's scaleALOPECIA/HLG0G1G2G3G4n (%)6 (15%)15 (37.5%)7 (17.5%)10 (25%)2 (5%) Open table in a new tab Conclusions: Our results confirm previous evidences, showing that DCS is a good chance to keep hair during CT. Further trials are needed to refine pts selection and to improve the effect and tolerance.

e12016 Background: Alopecia (A) is one of the most emotionally distressing side effects of chemotherapy (CT). CT-induced A may lead to a negative body image, contributing to worsen the quality of life (QoL). The cancer treatments, especially in breast cancer (BC) patients (pts), often bring with it body image challenges, causing low self-esteem and having a detrimental effect on intimate relationships. DigniCap System (DCS), using the scalp cooling system, has been shown to reduce CT-induced A. The aim of this observational prospective study was to describe our experience. Methods: From February to December 2016, 31 consecutive pts with early stage BC who received anthracycline and/or taxane-based neoadjuvant or adjuvant treatment were enrolled. A nurse and a psychologist were dedicated. All pts received a psychological evaluation (EORTC QLQ-BR23; EORTC QLQ-C30; TAM; VAS). A has been graduated according to the Dean’s scale: G0 = no A; G1 < 25% A; G2 = 25–50% A; G3 = 50–75% A; G4 > 75% A. Results: A total of 31 pts were enrolled; 2 pts were not included because too early. Median age was 48 years (range 33-66). The majority of pts (96.5%) received adjuvant CT; only one patients received preoperative CT. Fifteen pts (51.7%) received 4 courses of EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 iv on day 1, every 21 days) followed by 12 courses of paclitaxel (P) (80 mg/m2 iv weekly); the remaining pts received 4 courses of EC (n = 13; 44.8%) or P and concurrent trastuzumab (2 mg/Kg iv; loading dose 4 mg/kg) for 12 consecutive doses (n = 1; 3.4%). All grade of A was observed in 96.5% (n = 28): G1 in 15 pts (51.7%), G2 in 5 pts (17%), G3 in 7 pts (24.1%) and G4 in 1 pt (3.4%). Among G1/2 DCS-related side effects, sore scalp and coldness were the main toxicity (52%). The other adverse events (AEs) were: headache G1/2 (44.8%); neck pain (34.5%) and heavy head (41.4%). No serious AEs were reported. Overall, 7% (n = 2) of pts discontinued DCS because of unsatisfactory hair preservation (n = 1) and headache (n = 1). Conclusions: Our results confirm previous evidences, showing that DCS is a good chance to keep hair during CT. In particular, it is interesting that 26 pts (89.6%) did not use wig or head cover.

Background: Approximately 5-10% of breast (BC) and ovarian cancers (OC) are hereditary, and are characterized by aggressive disease and early age of onset. Mutation of BRCA1 or BRCA2 genes are present in 30% of hereditary BC and OC. BRCA1/2 mutations substantially increase the lifetime risk of developing BC and OC. The purpose of our study is to describe the percentage of BRCA mutations in patients (pts) with BC or OC treated in our institution. Materials (patients) and methods: Three hundred seventy-seven pts (372 women and 5 men) with BC (n = 313; 83%), with OC (n = 60;16%) or BC plus OC (n = 4; 1%) were included in the analysis. We collected data about primary site of cancer, baseline clinical characteristics, BRCA1/2 status and family history of cancer in an anonymized dedicated database. DNA was extracted from the pts peripheral blood. We used multiplex ligation-dependent probe amplification (MLPA) to screen mutations in BRCA1 and BRCA2. Results: Of the 377 pts analyzed, 68 (18%) were BRCA1/BRCA2 mutated, 39 (10.3%) at BRCA1 gene and 27(7.1%) at BRCA2; only one subject (0.3%) had both BRCA1 and BRCA2 mutations. Among BC pts, 56 (17.6%) had triple negative (TN) disease and BRCA1/2 mutations were present in 20 (35.7%) of these: 17 TNBC pts had BRCA1 (85%) and 3 (15%) BRCA2 mutation. In 377 pts the most frequent BRCA 1/2 mutation was c.5266dupC (n = 29; 42.6). In TNBC pts c.5266dupC mutations constitutes about 88.2% of the BRCA1 pathogenic mutations. Conclusions: Different ethnic and geographical Countries have different BRCA1/2 mutation spectrum and prevalence. Very few data have been published regarding on geographical distribution in families with BRCA1/2 mutations in Italy, and particularly in South of Italy. The BRCA1 mutation c.5266dupC was originally described as a founder mutation in the Ashkenazi Jewish (AJ) population; however, this mutation is also present in Europe, Brazil and North America. The high incidence of c.5266dupC mutation in our pts may be linked to international migration flows. Understanding genetic predisposition to develop BC and OC may contribute to refine more cost-effective prevention and screening measures in a high-risk population.

Background: Hereditary breast cancer (BC) has become a popular topic in recent years; in this setting the availability of early detection is key to survival. Approximately 5-10% of BC are hereditary, and are characterized by aggressive/bilateral disease and early age of onset. The aim of our observational study was to describe the percentage of BRCA mutations in patients (pts) with BC treated in Medical Oncology Department (MDO) of Brindisi, Italian Salento. Materials (patients) and methods: A total of 317 consecutive pts (312 women and 5 men) were tested for analysis, according to national AIOM guidelines 2016. All pts had BC diagnosis and 4 pts (1,5%) had both BC and ovarian cancer (OC). Data about baseline characteristics, treatment, BRCA1/2 status and family history of cancer were collected according to the local Ethical Committee guidelines. We used multiplex ligation-dependent probe amplification (MLPA) to screen mutations in BRCA1 and BRCA2 in serum DNA samples. Results: Of the 317 pts analyzed, 55 (17.3%) were BRCA1/BRCA2 mutated, 31 (9.8%) at BRCA1 gene and 23 (7,2%) at BRCA2; only one subject (0,3%) had both BRCA1 and BRCA2 mutations. Furthermore, 56 pts (17,6%) had triple negative (TN) disease, and BRCA1/2 mutations were present in 20 (35.7%) of these: 17 TNBC pts had BRCA1 (85%) and 3 (15%) BRCA2 mutation. The most frequent mutation was c.5266dupC; this alteration represented 83.8% (n = 26) of the BRCA1 mutations and 47.37% of all mutations identified. In TNBC pts, the c.5266dupC mutations constitutes about 88.2% (n = 15). Conclusions: Few data have been published regarding on anthropological and geographical distribution in families with BRCA1/BRCA2 mutations in Italy, and particularly in Mediterranean population. The BRCA1 c.5266dupC mutation was first described in the Ashkenazi Jewish (AJ) population; however, this alteration is also present in Europe, Brazil and North America. The high incidence of c.5266dupC mutation in our pts may be linked to the presence in Salento of Jewish communities in the Middle Age. Actually there is no knowledge of organized Jewish settlements in this Area. Different ethnic and geographical regions have different BRCA1/2 mutation prevalence: understanding genetic predisposition to BC may contribute to definition of more cost-effective screening measures in population.

e11571 Background: Clinical activity of lapatinib-capecitabine has been well documented in advanced breast cancer (ABC). However, cutaneous and gastro-intestinal toxicity may interfere with the optimal treatment delivery. We report efficacy and safety data of the combination of lapatinib and metronomic capecitabine in a retrospective cohort of HER-2 positive ABC patients (pts). Methods: Pts treated with lapatinib (Lap, 1250 mg/daily) plus capecitabine (Cap, 1500 mg/daily) were included. Data on overall response rate (ORR), progression free survival (PFS), clinical benefit rate (CBR = partial response PR+ complete response CR + prolonged stable disease SD ≥ 24 weeks), overall survival (OS) and tolerability were reported. Results: In this observational cohort study 24 pts with ABC from a single Institutionwho received Lap/Cap modified schedule from November 2009 to December 2014were enrolled. Twenty pts were evaluable for response and 23 for toxicity. In our analysis 52.5% pts received ≥ 3 previous lines for advanced disease. Median age was 51 years (range 34-70), PS was 0-1 in 100%, visceral metastases were present in most patients (84%). Median follow-up was 25 months (range 1-53). The ORR was 40% (95% CI, 19-64%), with 2 CR and 6 PR. Four patients had prolonged SD (21%). The CBR was achieved in 60% (95% CI , 36%-80%). Four progressions disease (PD) were observed (20%). Median PFS was 4.8 months (range 1.4- 28.7+), median OS 27 months (range 3.0-52.3+). Four-year OS was 75%. Main toxicities were grade 2 hand-foot syndrome (HFS) in 7 pts (30%), grade 2 diarrhea in 5 pts (21%), ungueal alterations G2 in 3 pts (13%), grade 2 rash in 2 pts (8%). No grade 3 or 4 specific Lap/Cap induced toxicities were reported, mainly in terms of photosensitivity reaction during sun exposure. Three pts had dose reduction for gastrointestinal toxicity and 2 treatment discontinuation for persistent diarrhea G2. Conclusions: Efficacy and tolerabilityof Lap/Cap modified schedule are encouraging. This combination might be considered when low toxicity burden is advisable and could allow sun exposure contrary to literature data.

Background: The efficacy of lapatinib (Lap) plus capecitabine (Cap) in HER2 amplified advanced breast cancer (ABC) has been widely reported in literature. However, cutaneous and gastro-intestinal toxicity may interfere with the optimal treatment delivery. Methods: In this observational cohort study, 24 patients (pts) with HER2 amplified ABC from a single Institution who received Lap/continuous metronomic Cap modified schedule (Lap, 1250 mg/daily, plus Cap, 1500 mg/daily) were enrolled from November 2009 to December 2014. We report data on efficacy and tolerability . Results: In our analysis, 23 pts were evaluable for toxicity and 20 pts for response. Median age was 51 years (range 34-70). Median follow-up was 25 months (range 1-53). The majority of pts (84%) had visceral metastases and about half of pts (52.5%) received ≥ 3 previous lines for advanced disease. The overall response rate (ORR) was 40%, with 2 complete responses (CR) and 6 partial response (PR). Four pts had prolonged stable disease (SD) (21%). The clinical benefit rate (CBR= partial response PR + complete response CR + prolonged stable disease SD ≥ 24 weeks) was achieved in 60% of pts. Four progressive disease (PD) were observed (20%). Median progression free survival (PFS) was 4.8 months, median overall survival (OS) 27 months. Treatment was well tolerated, mainly in terms of photosensitivity reaction during sun exposure. Main toxicities were grade 2 (G2): hand-foot syndrome (HFS) in 7 pts (30%), diarrhea in 5 pts (21%), ungueal alterations in 3 pts (13%), rash in 2 pts (8%). No grade 3 or 4 specific Lap/continuous metronomic Cap induced toxicities were reported. Three pts had dose reduction for gastrointestinal toxicity and 2 treatment discontinuations for persistent diarrhea G2. Conclusions: Our analysis showed that Lap/continuous metronomic Cap modifies schedule is active as treatment in HER2 positive ABC and minimally toxic. This combination might be considered when low toxicity burden is advisable and could allow sun exposure contrary to literature data.

Endocrine therapy is the recommended systemic therapy for hormone receptor (HR) positive metastatic breast cancer (MBC). However so far the limited number of endocrine agents and the onset of endocrine resistance have severely limited the therapeutic options for this patients. In the last years many targeted agents have been investigated to prevent or overcome endocrine resistance; only a few of them have been found effective in HR positive MBC, such as everolimus, CK4/6 inhibitors and HDAC inhibitors. Furthermore, translational medicine studies using next generation sequencing technologies have evaluated genetic variations of a broad panel of cancer-related genes and explored their correlations with targeted agents benefit. In some studies predictive biomarkers have been identified and many ongoing studies are evaluating the efficacy of targeted drugs in HR positive MBC patients selected for biomarkers or stratified by pathways amplification.

618 Background: Clinical activity of the combination of chemotherapy plus trastuzumab in HER2+ ABC has been well documented. We report the first results in terms of activity and safety of the combination of trastuzumab plus metronomic capecitabine and cyclophosphamide as first line therapy in HER-2 positive ABC. Methods: Patients (pts) at first relapse or with synchronous metastasis, were treated with trastuzumab (4 mg/kg, loading dose 6 mg/kg) plus oral capecitabine (1500mg/daily) and cyclophosphamide (50 mg/daily). Primary end-point was overall response rate (ORR), secondary end-points time to progression (TTP), clinical benefit rate (CBR; PR+ CR + prolonged SD for ≥ 24 weeks) and tolerability. The optimal two-stage design was applied. Results: A total of 31 pts with measurable ABC, tumors scored as +3 positive for HER-2 or FISH +, no pretreated with chemotherapy or trastuzumab for advanced disease have been enrolled, 28 actually valuable for response and toxicity. Median age was 59 years (range 42-87), visceral metastases were present in most patients (61%). Median number of cycles was 12 (range 1-37+). The ORR was 61 % (95% CI, 41-78%), with 1 CR (3.6 %) and 16 PR (57.1%). 9 patients had prolonged SD (32%). The CBR was 82.1% (95% CI , 63%-94%). Five progressions were observed (18%). Median TTP was 7 months (range 2- 19 + months). Ten pts received more than 20 courses. Worst toxicities were grade 2 hand-foot syndrome in 4 pts, grade 2 anemia in 4 pts, grade 2 nausea in 2 pts and diarrhea grade 3 in 1 pt. Cardiac toxicity grade 2 in 1 pts. Alopecia was not reported. Conclusions: Combination of trastuzumab and low dose metronomic oral chemotherapy in HER-2 + breast cancer has shown clinical activity. The tolerability was excellent and allowed the prolonged delivery of the combination. Thus, the patients accrual is ongoing to the pre-set target of 66 patients. Clinical trial information: 2009-017083-16.

Background: To explore clinical outcomes and cardiac safety of continuous antiHer2 therapy. Patients and methods: This retrospective study evaluates overall survival (OS), time to treatment failure (TTF), and cardiac safety of 80 consecutive Her2-positive metastatic breast cancer (MBC) patients that received >= 12 months of therapy with trastuzumab, followed by lapatinib-based or trastuzumab-based therapy.Results: All patients received trastuzumab as first antiHer2 therapy; 54% received lapatinib in the second or subsequent line. Median OS was 34 months (12-120 months). Median OS was 48 months in the subgroup of 43 patients who received lapatinib and 26 months in the 37 patients who did not. Median TTF was shorter for lapatinib. There were three cardiac events and trastuzumab-based chemotherapy (CT) was interrupted in one patient because left ventricular ejection fraction (LVEF) decreased to <= 40%.Conclusion: Continuous antiHer2 therapy provides good clinical outcomes, especially in those patients who received lapatinib. Cardiac dysfunction was a rare event, reversible, associated to trastuzumab and not related to treatment duration.

e18545 Background: Maintenance chemotherapy with pemetrexed is not the standard treatment of choice in patients with locally advanced or metastatic epiteliomorfe malignant pleural mesothelioma (EMPM). We would assess the safety and efficacy of a treatment with pemetrexed until progression disease after 4 or 6 cycles of induction therapy with or without platin. Methods: From July 2008 to September 2012, 21 patients (18 males and 3 females with a median age of 67 years range 58-84) with locally advanced or metastatic epiteliomorfe malignant pleural mesothelioma (EMPM) were enrolled. In all patients histology was epiteliomorfe malignant mesothelioma. Only 15 patients (71,4%) had a PS 0 whereas 6 (28,6%) had a PS 1. All patients received an induction therapy with or without platin. Each patient received an average of 5,6 cycles of induction chemotherapy. Then all patients received a maintenance chemotherapy with pemetrexed 500 mg/mq intavenously over 10 minutes every 3 weeks. Each patient received an average of 7,3 cycles of maintenance chemotherapy. All patients received folic acid and vitamin B12 supplementation to improve safety. Results: At the time of analysis all patients were evaluable for response. Fourteen patients (66,6 %) had a partial response and two of these underwent surgery and obtained a complete response. Six patients (28,5%) had a stable disease. The median overall survival was 13 months, while median progression-free survival was 11 months. Grade 2-3 of WHO haematological toxicities (anemia and neutropenia) occurred in 4 patient (19%). We also observed grade 2-3 of WHO gastrointestinal toxicities (diarrhea, nausea and vomiting) in 2 patient (9.5%). Grade 2 of lack of appetite and asthenia occurred in 3 patients (14.3%). Conclusions: Our data show that a maintenance chemotherapy with pemetrexed in EMPM resulted in a moderate overall survival (13 months). These results indicate that patients with EMPM could benefit from a maintenance treatment with pemetrexed.

Platinum-based chemotherapy is the standard treatment for patients with advanced non-small cell lung cancer (NSCLC), but the evidence of its efficacy among ECOG performance status (PS)2 patients is weak because these patients are usually excluded from clinical trials; concern exists about tolerability and feasibility of standard chemotherapy in these patients. No prospective randomized trial has tested the addition of cisplatin to single-agent chemotherapy in patients with advanced NSCLC and PS2. CAPPA-2 was a multicenter, randomized phase 3 study for first-line treatment of PS2 patients with advanced NSCLC. Patients, aged 18-70, were eligible if they had stage IV or IIIB with malignant pleural effusion or metastatic supraclavicular nodes (TNM VI edition) and adequate organ function. Patients in standard arm received gemcitabine 1200 mg/m(2) days 1 and 8. Patients in experimental arm received cisplatin 60 mg/m(2) day 1 plus gemcitabine 1000 mg/m(2) days 1 and 8. All treatments were repeated every 3 weeks, up to 4 cycles, unless disease progression or unacceptable toxicity. Primary endpoint was overall survival (OS). To have 80% power of detecting hazard ratio (HR) 0.71, corresponding to an increase in median OS from 4.8 to 6.8 months, 285 deaths were required. The study was stopped in June 2012 after the enrolment of 57 patients, due to the slow accrual and the report of positive results from a similar study. Median OS was 3.0 months with single-agent gemcitabine and 5.9 months with cisplatin plus gemcitabine (HR 0.52, 95% CI 0.28-0.98, p = 0.039). Combination chemotherapy produced longer PFS (median 1.7 vs. 3.3 months, HR 0.49, 95% CI 0.27-0.89, p = 0.017) and higher response rate (4% vs. 18%, p = 0.19), without substantial increase in toxicity. The addition of cisplatin to single-agent gemcitabine improves survival as first-line treatment of PS2 patients with advanced NSCLC.

Aims and background Few data describe the activity of panitumumab after cetuximab-irinotecan-based regimen failure in patients with KRAS wild-type metastatic colorectal cancer (WT MCRC). Methods The aim of this study is to assess if panitumumab has some activity in this setting. Results We retrospectively analyzed 25 patients with KRAS WT MCRC who received panitumumab from July 2009 to January 2013 after progression on cetuximab. All patients had previously received cetuximab and irinotecan (20 patients) or oxaliplatin (5 patients). We withdrew cetuximab for intolerance in 4 patients (16%). Twenty-one patients (84%) who had previously responded to cetuximab (overall response rate [ORR] plus stable disease ≥5 months) received panitumumab off-label after progression on cetuximab because they were strongly motivated to continue treatment without chemotherapy. The median number of cycles of panitumumab was 7 (range 1-54). Only 20 patients were evaluable for ORR (5 patients received 1-2 cycles and then died). We observed 1 (5%) partial response, 5 (25%) stable disease, median duration 9 months. Median progression-free survival (PFS) and overall survival (OS) were 5 (3-28) and 8 (5-41) months, respectively. All patients were evaluable for toxicity. No patients developed anemia or neutropenia. One patient (4%) developed grade 2 thrombocytopenia, 8 patients (32%) grade 2-3 dry skin or rash, and 2 patients (8%) grade 2 nausea-vomiting (Common Terminology Criteria for Adverse Events version 4.03). Conclusions Our data, with all the limits of a retrospective analysis, show longer PFS and OS as compared to other series in the same setting, demonstrating that panitumumab has treatment effectiveness in patients with KRAS WT MCRC who progressed on prior cetuximab. Further confirmatory prospective studies with a larger series of patients are necessary.

Treatment of elderly or poor performance status (PS) patients with advanced non-small-cell lung cancer (NSCLC) is a debated topic. To evaluate the efficacy of a modified schedule of gemcitabine, 59 patients unfit for platinum were enrolled. Mean age was 75.8 years and 41 % of patients had an ECOG PS 2. Gemcitabine was given at 1000 mg/m(2) on days 1, 8 each 28. Most of patients received gemcitabine as first-line chemotherapy, which was continued as maintenance over 6 cycles in responding and stable patients. Median overall survival (OS) and progression-free survival (PFS) were 7.2 and 5 months. In those 45 evaluable patients, treatment resulted in 1 complete remission (CR), 9 partial remissions (PR), and 20 stable diseases (SDs) with a response rate (CR + PR) of 22 % and a clinical benefit (CR + PR + SD) of 68 %. Gemcitabine was continued over 6 cycles in 16 patients (27 %). These patients were treated until progression with a mean of further 8.6 cycles. Median OS and PFS in these selected patients were 19 and 16 months. The toxicity profile was excellent with only 8 % of overall G3-G4 adverse events. None of the 16 patients under the maintenance phase reported significant toxicity. Gemcitabine given at a lower dose intensity than standard should be considered as valuable therapeutic option in elderly or poor PS patients with advanced NSCLC unfit for platinum. Extending the treatment beyond 6 cycles in responding patients is feasible and may prolong survival.

ABSTRACT Introduction Preoperative radiotherapy (RT) combined with capecitabine is often the treatment of choice in patients with locally advanced rectal cancer (LARC). We would assess the safety and efficacy of a metronomic schedule of capecitabine combined with preoperative radiotherapy. Methods From January 2009 to January 2012, 22 patients (19 males and 3 females with a median age of 71 years range 44-82) with locally advanced rectal cancer (LARC) (cT4N2 22.7%, cT4N0 9.1%, cT3N2 22.7%, cT3N1 18.2%, cT3N0 22.7% and cT3Nx 4.6%) were enrolled. In all patients histology was adenocarcinoma. Only 11 patients (50.0%) had a PS 0 whereas 10 (45.5%) had PS 1 and 1 patient (4.5%) PS 2. One group (16 patients) received pelvic RT (45Gy, 5 days/week, for 5 weeks) and another group (6 patients) received pelvic RT plus boost on rectum (45 Gy+boost 5.4 Gy, 5 days/week, for 5 weeks). All patients received preoperative chemotherapy with metronomic capecitabine 1500 mg/die, in a single dose within half an hour lunch, for 5 weeks for all the course of radiotherapy. Fourteen patients underwent surgery in 6-8 weeks after completion of the chemoradiotherapy, four patients after 8 weeks, two patients did not underwent surgery (too early) and two patients were lost to follow-up. Results At the time of analysis 18 patients were evaluable for response. Downstaging was ypT4N1 5.60%, ypT3N2 11.1%, ypT3N1 5.60%, ypT3N0 33.3%, ypT2N1 5.60% and ypT2N0 38.8%. Only 8 patients achieved a downsizing between 0-1 cm whereas 10 patients between 2-3 cm. Grade 1 of WHO haematological toxicities (leucopenia) occurred in 1 patient (4.5%) and grade 1 of not-neutropenic fever occurred in 1 patient (4.5%). We also observed grade 3-4 of WHO gastrointestinal toxicities (diarrhea) only in 1 patient (4.5%) whereas grade 1-2 occurred in 7 patients (31.8%). Grade 2 of lack of appetite and asthenia occurred in 3 patients (13.6%). Overall, we did not observe any hand-foot syndrome, nausea and vomiting. Conclusion Our data show that a schedule of metronomic capecitabine combined with preoperative radiotherapy may be beneficial in terms of downstaging of disease and tolerability in patients with locally advanced rectal cancer (LARC).

e11001 Background: Overweight at the time of EBC diagnosis has been linked frequently to poorer survival in most studies and some evidence suggests that women who gain weight after breast cancer diagnosis are at increased risk of cancer recurrence and death. Most previous studies on this topic have relied on retrospective chart reviews. The aim of this prospective, observational, single-center study is to determine whether weight at diagnosis and weight gain after EBC treatment can be predictive of BC recurrence. Methods: From December 1990 to January 2012, the study included atotal of 311 EBC patients (stage I-IIIa).We assessed weight and body mass index (BMI=kg/m2) at baseline (≤ 1 month after surgery) and 24 months after completion of treatment (chemotherapy ± radiotherapy). The chi square test (X2) was conducted to determine if a significant correlation exists between BC recurrence and 3 categories of BMI at diagnosis (lean weight: BMI <25; overweight: BMI 25-30; obese: BMI >25) and BC recurrence and weight changes after EBC treatment (loss of <1 kg/m2; loss of ≥ 1 kg/m2; gain of <2kg/m2; gain of >2 kg/m2). Results: Median age was 56 years (range28-81); 68% of patients were postmenopausal, stage I-II in 88%; ER+/PGR+ in 66%; ER+/PGR- in 12%; HER2+ in 14%; 72% underwent conservative surgery+radiotherapy; 57% received chemotherapy (CT) and 78% received endocrine therapy alone or after CT. Median BMI at diagnosis was 27.03, after treatment 28.04. After a median follow-up of 13 years 104 patients recurred. Statistical analysis is reported in the table. Conclusions: Our findings show that EBC patients gain weight after treatment. No significant correlation was found between weight at diagnosis, weight changes after EBC treatment and recurrence. At ASCO meeting we will report results of the prognostic associations of baseline biological features, menopausal status and comorbid disease. [Table: see text]

e18048 Background: Erlotinib is an oral tyrosine kinase inhibitor, approved for treatment of advanced NSCLC after the failure of more than 1 or 2 previous chemotherapy regimens. Its efficacy is comparable to that of chemotherapy, however, some concerns have been raised on its activity in pts with poor PS or in those not harboring EGFR mutation. Methods: Wereviewed the medical records of pts treated with erlotinib in the last 5 years in two Oncologic Centers of South Italy, with the aim to correlate response to pts characteristics. Results: Since January 2006 we have treated with erlotinib 388 pts affected by stage IIIb-IV NSCLC as 2nd, 3rd or 4th line of therapy. Median age was 67 (range 23-90), 300 were males and 88 women. Histology was ADK in 214 (55.2 %), SQM in 129 (33.2%) BAL in 12 (3.1%) and other in 33 (8.5%). Stage IIIb/IV was 66/322 (17%/83%). PS was 0 in 90 (23.5%), 1 in 214 (57.4%), 2 in 60 (15.5%) and 3 in 14 (3.6%) pts, respectively. Smoking status was: never smoker 60 (15.6%), ex smoker 276 (71%), currently smoker 52 (13.4%). With regard to the line of therapy, 250 pts (64%) were treated as 2nd line, 113 (29.1%) as 3rd line and 25 (6.5%) as 4th line. Overall, 117 pts (30%) received only the first drug supply and were lost to follow-up, 131 (33.4%) received 2 or 3 drug supplies, 134 (35.7%%) 4-30 drug supplies and 5 pts (0.9%) > 30 drug supplies, respectively. According to RECIST Criteria, 20/256 evaluable pts (11 too early, 121 not evaluable) achieved PR (7.8%), 74 SD (28.9%) and 162 (63.2%) progressed. The characteristics of the responding pts were as follows: 12 women and 8 men, 15 ADK, 4 SQM and 1 other histology (undifferentiated), 9 never smoker, 10 ex smoker and 1 current smoker, PS 0/1/2 in 8/9/3 pts; line of therapy 2nd/3rd/4th in 16/4/0. The median duration of response was 10 months (range 3 to >30). Median duration of SD was 9 months. Responding pts had a median survival of 28 months (range 3-105). Conclusions: These retrospective data suggest a more cautious usage of the drug, in order to avoid the huge number of pts lost to follow-up. In fact, erlotinib should not be prescribed in pts with poor PS and in lines beyond the 3rd, unless for pts harboring EGFR mutation.

Patients and methods: From July 2005 until November 2008, 1,001 patients (990 eligible) were randomized to receive 3 cycles of epirubicin 110 mg/m followed by 3 cycles of paclitaxel 200 mg/m followed by 3 cycles of CMF (cyclophosphamide 840 mg/m; methotrexate 57 mg/m; fluorouracil 840 mg/m) with G-CSF support (Group A; 333 patients) or to 3 cycles of epirubicin followed by 3 cycles of CMF, as in Group A, followed 3 weeks later by 9 weekly cycles of docetaxel 35 mg/m (Group B; 331 patients) or 9 weekly cycles of paclitaxel 80 mg/m (Group C; 328 patients). Radiation and hormonal therapy were given after the completion of chemotherapy. Trastuzumab was administered for 1 year to all HER2-positive patients post radiation.

INTRODUCTION:The chance to take advantage of genetic defects of cancer cells is a promising clinical tool in breast cancer therapy. Among the genetic aberrations, dysfunctions in DNA repair mechanisms are quite common and suitable for an attractive antitumor effect. Poly (ADP-ribose) polymerase I (PARP-1) is an enzyme with many functions in transcriptions and cell cycle regulation and in coordination of cellular response to DNA damage. Its involvement in tumorigenesis is witnessed by the overexpression found in different primary human tumors, where the increased enzymatic activity leads to cancer cell protection against DNA damage and instability. Therefore, activity of PARP and the opportunity to block it, mainly in cancer cells also deficient in other mechanisms of repair, are promising.AREAS COVERED:In this review, areas covered include the main DNA repair mechanisms, the role of PARP enzymatic activity in diverse cell pathways as well as the preclinical and clinical data with PARP inhibitors.EXPERT OPINION:Despite the theoretical role of PARP inhibitors as therapeutic strategy in specific subtypes of breast cancer (hereditary BRCA1/BRCA2 mutation-related cancers and sporadic triple-negative breast cancer), questions are still open. More exhaustive knowledge is needed about other important functions of PARPs in cellular homeostasis and about escape mechanisms of cancer cells to inhibitory effect of PARP inhibitors.