julilili42/papers huggingface dataset:
Efficacy of abiraterone acetate in the treatment of castration-resistant prostate cancer: Early results from the German compassionate-use program.
2012-05-20

e15195 Background: Abiraterone acetate (AA) plus prednisone (P) has demonstrated an improved survival of patients with castration-resistant prostate cancer (CRPC) compared to placebo plus P in a large phase III trial. In Germany, patients were able to receive AA within a compassionate-use program (CUP). Here, we report the first results of the program. Methods: Patients were eligible for the CUP if they progressed on or after at least one cytotoxic chemotherapy regimens. For CUP entry, patients were considered to have disease progression if they had radiographic evidence of disease progression in soft tissue or bone with or without PSA-progression and ongoing androgen deprivation. Patients received AA 1000mg daily plus prednisone 5mg BID until progression of disease or unacceptable toxicity. Results: Between 02-05/2011, 398 patients were registered for the CUP in Germany. Data from 191/350 (47.9%) of the patients treated at 10 different sites were available for evaluation of efficacy. Median age was 70.72yrs (52.35-87.61) and patients received a median of 1 (1-4) chemotherapy lines prior to CUP entry. Median PSA at baseline was 220.5 ng/ml (0.47-4245); 168 (88%) of patients presented with bone metastasis. With regard to efficacy, 64/191 (33.5%) of the patients showed an unconfirmed PSA-response ≥50%. At a median follow-up of 5.3 months, 51/191 (26.7%) patients had died, resulting in a median PSA-progression free and overall survival of 8.3 and 10.61 months, respectively. In a subset of patients (71/191, 37.2%) data regarding objective response was available with 25/71 (35.2%) achieving an objective response. Data from 114 pts. revealed fatigue (20.3%), hot flushes (15.8%), edema (10.6%), elevated liver enzymes (8.0%) and asthenia (7.9%) being the most frequent toxicities (any grade). Conclusions: Treatment of CRPC patients with AA outside controlled clinical trials leads to considerable PSA- and objective response rates with a favourable toxicity profile, comparable to the results from COU-AA-301 registration trial. Due to the short median follow-up, conclusions regarding PSA-progression free and overall survival may not be drawn.
Interim safety results from a phase II/III trial with 5-FU, oxaliplatin, and docetaxel (FLOT) versus epirubicin, cisplatin, and 5-FU (ECF) in patients with locally advanced, resectable gastric/oesophagogastric junction (OGJ) cancer: A study of the AIO.
2012-05-20

4083 Background: Perioperative ECF is a standard treatment for localized gastric/OGJ adenocarcinoma. However, 5-year survival rate remain below 40%. The FLOT regime is an effective new combination with pathologic response rates in the 15% range. This phase II/III study compares both regimens in resectable stages. Methods: Pts are stratified by different baseline criteria and randomized to either 3 + 3 perioperative cycles of ECF (Epirubicin 50 mg/m 2 , d1 Cisplatin 60 mg/m2, d1 5-FU 200 mg/m2, d1-d21, qd21) or 4 + 4 cycles of perioperative FLOT (Docetaxel 50mg/m2, d1 5-FU 2600 mg/m2, d1 leucovorin 200 mg/m2, d1 Oxaliplatin 85 mg/m2, d1, qd14). 5-FU can be replaced by Capecitabine in the ECF-arm (ECX). This is a preplanned toxicity analysis after 200 pts in order to decide whether to continue to a phase III trial. Results: 202 pts have been randomized so far. Median age is 62 yrs; 79% of pts are male. The Primaries were Gastric in 43.4%, OGJ in 53.2% and not evaluable/documented in 3.4% of pts. 190 pts were eligible for the safety analyses. Median no. of preoperative cycles was 3 and 4 with ECF/ECX and FLOT, respectively, and 68.7% vs. 66.0% of pts (ECF/ECX vs. FLOT) started postoperative chemotherapy (ct). Grade 3/4 side effects were observed in 52.1% of ECF/ECX and 59.6% of FLOT pts with no significant differences between arms regarding individual grade 3/4 toxicities. Thromboembolic events occurred in 14.5% vs. 8.5% in pts with ECF/ECX vs. FLOT (p=.25). Serious adverse events occurred in 60.3% vs. 39.7% of pts with ECF/ECX vs. FLOT. Preoperative delay/interruptions of ct were observed in 74.0% vs. 61.7% of pts with ECF/ECX vs. FLOT (p=.07). Dose modifications of preoperative ct were performed in 28.1% vs. 22.3% of treatment cycles with ECF/ECX vs. FLOT, respectively. 121 pts underwent surgery. Severe surgical morbidity was similar in both arms (ECF/ECX, 15.8%; FLOT, 14.1%). Surgical mortality was observed in 2 and 1 pts with ECF/ECX and FLOT. Toxic deaths were observed in 1 pt each. Conclusions: Perioperative FLOT is feasible and safe. This supports the continuation of the trial as a phase III.
Compliance and arthralgias in clinical therapy (COMPACT): Assessment of the incidence of arthralgia, therapy costs, and compliance in the first year of adjuvant anastrozole.
2012-05-20

e11040^ Background: Aromatase Inhibitors (AI) are well established as adjuvant endocrine treatment for postmenopausal women with HR+ early breast cancer (EBC). However, clinical trial data show higher frequently of arthralgia with AI than tamoxifen. As arthralgia may be greatly influencing compliance to adjuvant therapy, we designed a prospective trial to collect real world data on the effects of AI-associated arthralgia on patient compliance, patient outcomes and treatment costs of arthralgia. Methods: COMPACT is an open, prospective non-interventional study (NCT00857012) assessing the incidence of arthralgia, therapy costs, and compliance within the first year of adjuvant anastrozole (ANA) therapy in postmenopausal patients with HR+ EBC. Patients on adjuvant ANA for 3-6 months were enrolled and stratified by initial adjuvant ANA or switch from tamoxifen. All patients receive regular standardized information about breast cancer from baseline to week 20 to support treatment compliance. Data on demographics, arthralgia, therapy thereof and QoL are collected at baseline, 3, 6 and 9 months. Primary endpoints are scaled data on arthralgia and compliance within the first year of ANA therapy. Secondary endpoints include the incidence of arthralgia, therapy costs, reasons for non-compliance, and influence of arthralgia on clinical outcome. Results: From Apr 2009 to Mar 2011, 2313 patients were enrolled, 2007 on upfront ANA and 306 patients on switch therapy. The mean age was 64.5 years, mean BMI 27.7. Only 16.8% had received HRT prior to their EBC. 41.5% had symptoms relating to skeleton or musculature, and 11.9% stated arthralgia existing prior to ANA. 13.1% reported a worsening of pre-existing arthralgias or new arthralgia after starting ANA. Predictors for non-adherence to AI and scaled data on arthralgia are under analysis. Conclusions: COMPACT aims to provide valid data on AI-associated arthralgia, treatment, treatment costs and compliance to AI. This may help to better inform patients and health care providers about these clinically important issues with the aim to improve adherence to adjuvant ANA, breast cancer outcomes, and therapy costs.
Accuracy of MRI, mammography (MG), and 2D and 3D ultrasound (2DUS/3DUS) in determining the pathologic tumor response after neoadjuvant chemotherapy (NACT) in breast cancer patients.
2012-05-20

1067 Background: The pathological tumor response in patients with locally advanced breast cancer to NACT is essential for survival and for surgical strategies. Therapy monitoring based on German recommendations is routinely performed by clinical examination, MG and 2DUS. The clinical value of MRI and 3DUS has not been established yet. The aim of the study was to determine the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) between the different imaging techniques in predicting postoperative histological tumor response after NACT. Methods: Patients with primary breast cancer (cT1-T4, cN0-1, M0) undergoing neoadjuvant chemotherapy between 2005 and 2010 were eligible for this prospective trial. The response was measured by MRI, MG, 2DUS and 3DUS for complete or partial remission versus stable disease after the last cycle of treatment and compared with the final pathological response. Patients with progressive disease were excluded from the study. Statistical analysis was done by calculating the accuracy of each imaging technique and the size difference between imaging and histological tumor size. Sensitivity, specificity, PPV and NPV were calculated for complete or partial pathological response. The study was approved by the local ethic committee (BCD001 194/2004). Results: 103 patients with the mean age of 47.7 (range 24.5 – 71.4) years were evaluated. The accuracy was 0.680 (95%CI: 0.580 -0.768) for MRI, 0.563 (95%CI: 0.453-0.669) for MG, 0.724 (95%CI: 0.618 -0.815) for 2DUS and 0.710 (95%CI: 0.588-0.813) for 3DUS. Sensitivity, specificity, PPV and NPV were 78%, 47%, 75% and 52% for MRI, 61%, 45%, 69% and 36% for MG, 93%, 23%, 74% and 60% for 2DUS, 94%, 19%, 73% and 57% for 3DUS. The mean (standard deviation) size difference was -1.8 mm (14.8) on MRI, 1.5 mm (26.0) on MG, -9.1mm (19.1) on 2DUS and for the volume difference -6916mm3 (15831) on 3DUS. Conclusions: The data suggest that 2DUS is sufficient in predicting tumor response between NACT treatment. MRI and MG are more accurate the 2DUS in predicting the tumor size for surgical planning.
Correlation of BMI with tumor stage in early breast cancer patients (pts): Pooled analysis of the German SUCCESS A, B, and C trials.
2012-05-20

1602 Background: Independent from known prognostic factors, e.g., tumor size and nodal status, obesity is a risk factor for poor disease free, distant disease free, and overall survival in breast cancer. The aim of this analysis was to examine the correlation of the body mass index (BMI) with tumor characteristics in early breast cancer. Methods: We analyzed the data of 7,997 pts with early, node positive or high risk node negative primary breast cancer treated with adjuvant taxan-based chemotherapy within the German multicenter phase III SUCCESS A, B, or C trials. The pts’ tumor stage at primary diagnosis was classified according to the UICC tumor-node-metastasis (TNM) classification. Additionally, the tumor’s hormone-receptor status and HER2/neu status were determined. Before enrollment into the study each patient was grouped according to the WHO global database on BMI. Contingency table methods were used to analyze the correlation of BMI and tumor characteristics. Results: Among the 7,997 pts 100 (1.3%) pts were underweight, 3,556 (44.5%) pts were normal weight, 2,569 (32.1%) pts were overweight and 1,772 (22.2%) were obese. Of all pts 4,508 pts (56.4%) suffered from a pT2-4 tumor, 4830 (60.4%) showed lymph node involvement (pN1-3) and 7509 (93.9%) had G2-3 tumors. 5839 pts (73.0%) showed positivity for ER or PR and 935 (11.7%) for HER2/neu. Overweight and obese pts had significantly larger tumors compared to pts with normal BMI (p&lt;0.0001; p&lt;0.0001). Furthermore, overweight and obesity were associated with a significantly higher rate of lymph node involvement (p=0.0001; p=0.0003) respectively. In contrast neither grading, tumor histology, ER/PR-status nor HER2/neu-overexpression were correlated with BMI. Conclusions: These data are the first to show in a large number of pts that both obese and overweight women suffering from primary breast cancer have significantly larger tumors and more often positive axillary lymph nodes. As there are no differences in tumor biology, the advanced tumor stage might be due to more difficult and delayed detection of breast cancer and lymph node lesions in these women.
Circulating tumor cells in metastatic breast cancer: Are they a strong and independent predictor of poor progression-free and overall survival?
2012-05-20

1090 Background: Circulating tumor cells (CTCs) are detected in 30–60% of patients with metastatic breast cancer (MBC). The aim of this prospective multi-center study was to evaluate the impact of CTCs on progression free survival (PFS) and overall survival (OS) in a large cohort of 486 patients with progressive metastatic disease. Methods: CTC levels were determined for 486 patients at nine German University Breast Cancer Centers between 12/2007 and 06/2011. Samples of 7.5 ml blood were taken before initiation of a new line of therapy and CTCs were enumerated using the CellSearch System (Veridex LLC, Raritan, NJ, USA). CTC status (≥ 5 CTCs vs. &lt; 5 CTCs per 7.5 ml blood) was assessed as a prognostic factor for PFS and OS using univariate (log-rank test) and multivariate (Cox regression model) statistical methods. Results: CTCs were detected in 205/486 (42%) patients. The median CTC count was 2 (range 0–6380) per 7.5 ml blood. The presence of ≥ 5 CTCs/7.5 ml blood did not correlate with any of the established clinicopathological factors except estrogen receptor status (p = 0.038). PFS and OS were both significantly shorter in patients with ≥ 5 CTCs/7.5 ml than in those with &lt; 5 CTCs/7.5 ml blood. PFS was 5.0 [95% CI 4.1–5.8] months vs.7.6 [95% CI 5.9–9.3] months, p &lt; 0.001; and OS was 15.0 [95% CI 13.5–16.5] months vs. 18.3 [95% CI 17.4–19.2] months, p &lt; 0.001. In the multivariate analysis considering all clinicopathological factors and the CTC status, independent predictors of reduced OS and PFS were site of metastasis (visceral vs. bone), number of metastatic sites (multiple sites vs. one site), and CTC status. Conclusions: The presence of ≥ 5 CTCs/7.5 ml blood is a strong and independent predictor of poor PFS and OS in patients with MBC.
Ipilimumab use in a named-patient program in metastatic melanoma: Experiences in 185 German patients.
2012-05-20

e19031 Background: The monoclonal antibody ipilimumab (ipi) showed a survival benefit in patients (pts) with unrespectable metastatic melanoma leading to its approval in 2011. Methods: Ipi was available in Germany before its approval in a Named-Patient Program for pts with unrespectable stage IV/IIIC melanoma. Pts were eligible if they failed at least one prior systemic treatment or were intolerant and did not suffer from auto-immune diseases. Ipi was administered at a dosage of 3mg/kg iv (4 cycles, q21). A re-induction was possible in case of progressive disease after initial clinical benefit. Results: Data from 185 pts (114 male; 71 female, median age: 60 [18-88Y]) of 12 German centers was evaluable. 175 pts actually received ipilimumab (100 pts received all 4 cycles). Reasons for early termination were: Reduced general condition (44%), tumor progression (28%), toxicity or wish of pts (11% each), and incompliance (6%). Response was evaluable in 161 pts. Objective response was observed in 17 pts (1 CR+16 PR), SD in 19 pts (disease control rate 22%). PD was diagnosed in 125 pts. Responding pts were characterized by less organs involved (p=0.028). Median survival for all pts was 8.1 months, 1-year overall survival was 36.4%. Median survival is not yet reached for pts with disease control (94% alive at last observation), whereas it was 5.5 for pts with PD (40% alive at last observation). Treatment was generally well tolerated. Severe (Grade 3+4) auto-immune related toxicities were diarrhea (15 pts), skin rash (1 pt) and hepatitis (1 pt). Aseptic meningitis was observed in 1 pt; and hypophysitis (Grade 2) likewise in 1 pt. Conclusions: Data coming from these 161 patients appear to be consistent with safety and efficacy profiles determined in large clinical trials. Tumor responses were induced in a subset of pts and associated with prolonged survival.
Phase II study of pemetrexed (Pem) and cisplatin (Cis) plus cetuximab (Cet) followed by Pem and Cet maintenance therapy in patients (Pts) with advanced nonsquamous non-small cell lung cancer (NSCLC).
2012-05-20

7554 Background: A prospective, nonrandomized, multicenter study was conducted to assess the effect of adding cet to pem and cis in pts with advanced nonsquamous NSCLC. Methods: 113 Caucasian performance status 0-1 pts received 1 st line pem (500 mg/m 2 ) and cis (75 mg/m 2 ) on day 1 (21d cycle) for 4-6 cycles and cet (400 mg/m 2 loading dose followed by 250 mg/m 2 ) weekly. Non-progressive pts received pem 500 mg/m 2 on day 1 (21d cycle) plus cet (250mg/m 2 weekly) until progression. Pts received vitamin B12/folic acid and dexamethasone. Primary endpoint was objective response rate (ORR) (RECIST 1.0). Secondary endpoints were progression free survival (PFS), 1 year survival rate, translational research (TR) and safety. Results: Pts’ characteristics: median age 59.7 years, 64% male, 50% PS 0, 92% stage IV, and 78% adenocarcinoma. All pts completed ≥ 1 cycle of induction therapy and 45% and 43% completed ≥ 1 cycle of maintenance with pem and cet, respectively. ORR (n=109) was 38.5% (80% CI 32.2-45.1), all partial responses. Disease control rate (response/stable disease) was 59.6% (80% CI: 53.1-65.9). Median PFS was 5.82 months (80% CI: 4.40-6.70). One year survival rate was 0.45 (80% CI: 0.39-0.51). Significant associations were seen between high EGFR by IHC and increased PFS (cytoplasm: HR=0.46, p=0.035; membrane: HR=0.41, p=0.008), and between high nuclear TTF-1 and increased ORR (OR=7.73, p=0.021) / PFS (HR=0.21, p&lt;0.001) / OS (HR=0.25, p=0.035). Of 113 pts evaluated for safety, 73 (64.6%) pts had drug related CTC Grade 3/4 adverse events (AE): most frequent were neutropenia (14.2%), rash (15%), and vomiting (8.8%). Drug related serious AEs were reported in 27.4% pts: most frequent were anemia (5.3%), neutropenia (5.3%), vomiting (3.5%), and rash, renal failure, diarrhea and fatigue (1.8% each). There were 2 potential on-study drug related deaths (sudden death and large intestinal perforation). Conclusions: Pem, cis and cet appeared efficacious and tolerable. These results support further evaluation in a randomized trial. The TR outcomes are hypothesis generating given the study’s size and nonrandomized nature.
A phase II-III clinical study with the immunomodulator MGN1703 in patients with advanced colorectal carcinoma: The IMPACT study.
2012-05-20

e14152 Background: Based on promising data from a phase 1 study of MGN1703 in patients with metastatic solid tumors including those with CRC, a phase 2-3 study was initiated in patients with advanced CRC having disease control after first-line therapy. MGN1703 is a synthetic DNA-based immunomodulator which acts as an agonist of toll-like receptor 9. The objective of the study is to assess efficacy and safety of treatment with MGN1703 in comparison to placebo. Methods: The IMPACT study is designed as an international, multicentric, randomized double-blind placebo-controlled phase 2-3 study. It is conducted in patients with advanced CRC showing disease control after 1st-line therapy with standard chemotherapy regimen. The study treatment is administered s.c. twice weekly (60 mg MGN1703 or placebo; ratio 2:1). The efficacy and safety of the study treatment will be evaluated based on extensive immunological tests, radiological assessment, safety laboratory results and assessments of the quality of life. The study treatment is continued until tumor progression, intolerable toxicity, exclusion criteria or withdrawal of consent. Results: Up to now, the patients received a maximum of 132 (mean: 32.1) treatment administrations, which equals 66 weeks. Drug-related adverse events (as assessed by the investigator) include mild fever, injection site itching, muscle aching, arthralgia, fatigue, paresthesia, rash, and moderate subfebril temperature and increased ANA in single patients. These represent only 16% of all adverse events reported in the study so far. Nine serious adverse events have been reported and only one was assessed as probably drug-related (“atypical pneumonia”). Local reactions reported in single patients include such symptoms as mild redness and swelling at injection site. Currently no laboratory or clinical signs of dose-limiting toxicities have been reported. Conclusions: The preliminary results of the ongoing clinical study in patients with advanced CRC show a good safety profile of the treatment with MGN1703 at the dosage of 60 mg. Most adverse events which were assessed as possibly drug-related belong to expected study drug reactions known for immune modulating drugs.
Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor cells in primary breast cancer patients.
2012-05-20

e21003 Background: An imbalance between cell proliferation and programmed cell death leads to tumor growth. Although most cytostatic agents used in systemic therapy of breast cancer induce an apoptosis in tumor cells leading to their destruction, a high ratio of apoptotic cells in primary breast cancer is correlated with poor prognosis. The purpose of this study was to investigate the incidence and prognostic significance of apoptotic disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer (PBC) patients. Methods: PBC patients who underwent primary surgery (PS) or were treated with neoadjuvant chemotherapy (NACT) between 01/2003 and 12/2007 were included into this prospective study. BM aspirates were analyzed by immunocytochemistry (M30 antibody) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. Patients without DTC in the BM were excluded from the study. Survival data were evaluated after a median follow up of 44 months. Results: BM aspirates of 383 PBC patients were analyzed. DTC were M30 positive in 82 of 298 (27%) patients who underwent PS and 41 of 85 (48%) patients treated with NACT. After NACT, the incidence of apoptotic cells in patients with complete/partial remission as compared to patients with stable/progressive disease was 63%/53% vs. 31%/0% (p=0.034). In the NACT group, M30-positive patients suffered less likely of a relapse than those without apoptotic DTC (7% vs. 23% of the events, p = 0.049). Inversely, overall survival in the PS group was significantly shorter in M30-positive as compared to M30-negative patients (75 months, 95% CI: 68-81 months vs. 84 months, 95% CI: 81-86 months; p = 0.008). Conclusions: Apoptotic DTC can be detected in breast cancer patients before and after systemic treatment. The presence of apoptotic DTC in BM of breast cancer patients can reflect the effects of neoadjuvant treatment. Spontaneous and chemotherapy-induced apoptosis may have different prognostic implications.