bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated results of a multicenter phase II trial of neoadjuvant docetaxel, carboplatin and capecitabine for inflammatory and locally advanced breast cancer (LABC)
Authors: Franco S. X. , Perez A. , Tan-Chiu E. , Gokce F. , Frankel C. , Schwartzberg L. S. , Krill E. , Jakub J. , Abramson N. , Vogel C. 
Published: March 2020

10685 Background: Neoadjuvant chemotherapy for the treatment of LABC has become the standard of care but the best combination is not established. The combination of docetaxel and capecitabine demonstrates synergism in patients(pts) with metastatic breast cancer (MBC). Recent studies support the value of platinum salts in LABC and MBC. Methods: pts with stage IIA-IIIC or inflammatory BC, EGOG PS 0–1, are eligible.We are evaluating the combination of weekly docetaxel 30mg/m2, carboplatin AUC2 on D1, 8,15 of a 4-week cycle plus capecitabine 625 mg/m2 BID given on days 5–18 (based on the upregulation of thymidine phosphorylase) for 4 cycles prior to surgery. The primary objective of this phase II trial is pCR rate in breast. Results: 39 of 48 pts have been enrolled from 7 centers. Median age 46 (range 26–75), stage II 41%, stage III 59%. Median baseline tumor is 5.4cm (range 2.1–15); 1pt inflammatory BC; 10 pts N2 disease (36%); 12 tumors were ER+, 20 ER-, and 5 Her-2+. To date, 2,377 doses (including daily capecitabine doses) were administered out of a total of 2,560 (93% of intended doses) with only 10 dose delays and 8 dose reductions. 37 pts are evaluable for toxicities. No grade IV toxicities were seen, grade III neutropenia was seen in 3/37(8%) and grade III fatigue in 1/37(3%). There were no episodes of neutropenic fever.The most common grade I/II toxicities were nausea in 57%, diarrhea 38%, fatigue 43%, epiphora 24%, mucositis 24% and hand-foot syndrome 3%. No death related treatments have been reported. 32 pts have completed definitive surgery. Objective clinical response is 94% with 53% cCR. 5 patients had pCRs in breast(16%) and 5 pCR in breast and axilla(16%). 9 pts (28%) have microscopic residual disease in the breast (<3mm). 14 pts had complete axillary clearance (44%). Conclusions: The preoperative combination of docetaxel, carboplatin and capecitabine is feasible with very good response rate and a very acceptable toxicity profile. Accrual is ongoing. No significant financial relationships to disclose.
Open labeled phase II observation study of gemcitabine plus cisplatin plus trastuzumab (GCT) in metastatic breast cancer patients with prior anthracyclines and taxanes exposures: Preliminary results
Authors: Demiray M. , Evrensel T. , Kanat O. , Kurt E. , Arslan M. , Gokgoz S. , Tolunay S. , Manavoglu O. 
Published: March 2020

10720 Background: Trastuzumab provides significant clinical benefit in HER2 positive metastatic breast cancer. Gemcitabine and cisplatin (GC) combination is attractive treatment options for anthracyclines-taxanes-pretreated metastatic breast cancer. These agents demonstrated synergistic activity and minimal overlapping toxicity. On the other hand, additional synergistic activity was observed with trastuzumab and GC. Methods: Histologically confirmed metastatic breast cancer patients with FISH positive tumors (HER2/choromosome 17 ≥2) were eligible if they were at least one measurable disease; ≥18 and ≤70 years; life expectancy >3 month; ECOG 0–2; prior anthracyclines and taxanes treatment but no prior trastuzumab therapy; adequate marrow, renal and hepatic function. Treatment schedule was as follows: Gemcitabine 1000 mg/m2 and cisplatin 30 mg/m2 d1, 8 every 3 weeks conjunction with trastuzumab 4 mg/kg d1 and 2 mg/kg for weekly. Chemotherapy was scheduled for up to eight cycles. Treatment was discontinued in case of progression or prohibitive toxicity. After progression additional regimen was administered with trastuzumab. Results: Eleven women were enrolled. All patients were eligible for toxicity and efficacy evaluations. Median age was 48 (range 28–64) years and median ECOG performance status was 0. Ten patients (90.9%) had visceral metastases, most commonly located in the liver (8 pts) and lung (4 pts). Estrogen receptor positivity was 63.6% (7 pts). A total of 80 cycles were delivered with a median of 8 cycles. Objective response rate was 54.5% (6 pts) with 27.2% (3 pts) complete response and 27.2% (3 pts) partial response. Stabile disease was achieved 36.3% (4 pts). Median time to progression and overall survival were 8 (95% CI: 3.97–12.02) and 18 months (95% CI: 15.89–20.10) respectively. Grade 3–4 toxicity was observed in 18.1% (2 pts). Treatment of one patient was discontinued due to grade 4 thrombocytopenia. Dose reductions due to myelotoxicity were performed in 1 (9.0%) patients. Conclusions: Our preliminary data shows that gemcitabine and cisplatin and trastuzumab combination regimen is effective and has manageable toxicity profile. No significant financial relationships to disclose.
FEC 60 adjuvant chemotherapy (AdCT) in breast cancer (BC) patients (Pts): 10-year follow-up results
Authors: Moura Silva F. , Tosello C. , Laloni M. T. , Andrade C. M. , Bertozzi A. , Vernaglia P. , Correa F. M. , Moraes R. P. , Goes J. S. 
Published: March 2020

10725 Background: To evaluate the efficacy of the Epirubicin as a part of the FEC60 AdCT in operable BrC patients in a Brazilian single-center. Methods: We verified retrospectively our experience with FEC 60 as AdCT in pre and postmenopausal, node positive and negative, pathologic stage I, II and III patients with BrC. Pts were submitted after surgery to receive Fluorouracil 600 mg/m2, Epirubicin 60 mg/m2 and Cyclophosphamide 600 mg/m2 every 28 days for 6 cycles. Pts who were ER+ and/or PR+ received Tamoxifen (TMX) 20 mg/day for 5 years after AdCT. Radiotherapy was also offered at the end of AdCT if indicated. All patients were evaluated in terms of 10 year (y) Disease Free Survival (DFS) and Overall Survival (OS). The most common toxicities (acute and chronic) and metastatic sites will also be reported. Results: Between July 1983 and December 1995 a total of 752 patients (ranging from 22 to 77 years old - median 47.7) were encountered and all of them were evaluated to 10 year (y) DFS and OS. Approximately 61% of these patients received adjuvant TMX. Pts in premenopausal and postmenopausal represented 62.5% and 37.5% respectively. 72 (11%) pts had pathological stage I; 353 (46%) pts had stage II and 327 (43%) had stage III. The 10y DFS was 70%, 46% and 19% for stage I, II and III respectively. The 10y OS after a minimal follow-up of 122.98 months was 74%, 48% and 20% for stage I, II and III respectively. Conclusions: Our results demonstrated that FEC 60 regimen is active and well tolerated in the adjuvant treatment for BrC pts. We had about 89% of stage II and III pts and in this population FEC60 regimen add benefit. Nevertheless, the randomized studies indicate that the greatest anticancer effect of Epirubicin requires doses ranging from 75 to 120 mg/m2, but due to economic reasons (we integrate the brazilian public healthy system) we could not offer dosages greater than 60 mg/m2. FEC 60 was feasible and offered reasonable results in our population in terms of 10y DFS and OS. No significant financial relationships to disclose.
Glioma patterns of care in Victoria from 1998–2000
Authors: Rosenthal M. , Drummond K. , Dally M. , Murphy M. , Cher L. , Ashley D. , Thursfield V. , Giles G. 
Published: March 2020

11521 Background: The management of Gliomas is complex and requires a multidisciplinary approach. The care of such patients (pts) may be variable. The State of Victoria has a population of approximately 4 million people and over 300 new glioma cases diagnosed annually. Methods: This was a retrospective cohort study conducted by surveying doctors involved in managing incident adult glioma cases identified from the population based Victorian Cancer Registry during 1998–2000. The survey was conducted in 2004–5 obtaining at least four years follow-up data on all pts. Results: 828 pts were considered eligible for this study. 264 pts (32%) were aged over 70 years and 92 (11%) were aged over 80 years. 105 (13%) did not have a histologic diagnosis and 473 (57%) had glioblastoma multiforme (GBM). Complete macroscopic resection was performed in 209 pts (25%). Of all pts with a glioma, 612 (74%) and 326 (54%) were referred at initial diagnosis for consideration of radiotherapy and chemotherapy respectively. In 473 pts with GBM, 406 (86%) and 147 (31%) pts were initially referred for consideration of radiotherapy and chemotherapy respectively. Only 39 pts(5%) were enrolled on a clinical trial. The median survival for pts with a GBM was 7.4 months with a 3% five-year survival. Conclusions: This is one of the largest ever-reported glioma management surveys. Much of the patient demographics and approach to treatment were expected and represent a reasonable “standard of care”. Importantly, this study emphasises the elderly nature of this patient population and identifies areas of concern including: absence of histologic diagnosis, lack of multi-disciplinary care and low clinical trial enrolment. No significant financial relationships to disclose.
A comparative study on capecitabine (Cape) pharmacokinetics (PK) in elderly or younger patients with metastatic breast (MBC) or colo-rectal cancer (CRC)
Authors: Longobardi C. , Strocchi E. , Di Fabio F. , Camaggi C. M. , Zoli N. , Martoni A. A. 
Published: March 2020

12003 Background: Cape is an efficient oral prodrug of 5FU in MBC and CRC. Unexpected severe toxicity in older patients (pts) was reported after standard dose of 2500mg/sm/day. About 70% of drug and metabolites are excreted with the urine and a 25% reduction of the dose is recommended if the pt has a creatinine clearance (CrCl) <50ml/min. However no prospective study has been done on Cape PK in the elderly pts. Methods: Between Oct 2004 and Nov 2005, 21 pts with MBC or CRC and age ≥70yrs or ≤60yrs who received Cape (1000 mg/sm bid for 14 days every 21 days) entered the study after giving signed informed consent. CrCl was calculated according to the Cockcroft-Gault method. Patient characteristics: 15 elderly pts (median 78 range71–84yrs), 6 younger pts (median 50.5 range 43–57yrs); 9 (42.9%) males and 12 (57.1%) females; median KPS 90 (range 70–100); 8 MBC pts (38%), 13 CRC pts (62%). Blood samples were taken on the first day of treatment at time 0 and at 0.25,0.5,1,2,3,4,5,6,8 hrs after the first drug administration and on 4th, 8th, 12th and 14th days in the morning. Plasma levels of Cape, 5DFUR, 5DFCR and 5FU were determined by a validated HPLC method and UV detection. Results: At present PK data after the first administration of Cape are available for 13 pts (9 elderly; 4 younger). The mean Cape and 5DFCR AUC0–8hr are higher in older patients (Cape 6653±2564.8 vs. 4427±2714.5; P=0.09; 5DFCR 8635±5197.1 vs. 6292±3813.6; P=0.26), while no evident differences are present for 5DFUR and 5FU. The same results are obtained both in pts with CrCl < and ≥ 50 ml/min. The ratios of DFUR_AUC to Cape_AUC and 5FU_AUC to Cape_AUC are conversely higher in younger than in older pts (mean: 2.2 vs 1.62). A large interindividual variability in the concentration/time curves is present for Cape and metabolites. Cape dose reduction because of G3 toxicity (2 hand-foot syndrome, 1 stomatitis) was performed in 3 elderly pts. Drug systemic exposure was higher in 2 of these pts independently of CrCl. Conclusions: The preliminary results of this PK study suggest that elderly patients treated with Cape at 1000 mg/sm/bid are more drug-exposed than younger patients, independently of renal function. PK analysis is ongoing for the remaining patients. No significant financial relationships to disclose.
Evaluation of 5-FU metabolism-relating enzyme gene expression levels using quantitative real-time RT-PCR from formalin fixed parafine embedded samples
Authors: Terashima M. , Odashima Y. , Ohtani S. , Soeta N. , Ohsuka F. , Kashimura S. , Hoshino Y. , Kogure M. , Gotoh M. , Danenberg K. D. , Danenberg P. V. 
Published: March 2020

13034 Background: We have previously reported that tumors with high orotate phosphoribosil transferase (OPRT) and low dihydropyrimidine dehydrogenase (DPD) mRNA expression levels showed remarkable sensitivity to 5-fluorouracil (5-FU) by real-time RT-PCR using fresh frozen (FF) tumor samples. However, the use of fresh frozen samples has some limitations. The use of formalin fixed parafine embedded (FFPE) samples has great advantage to apply these technologies for clinical settings. In order to investigate the feasibility of real-time RT-PCR from FFPE samples to predict sensitivitiy to 5-fluorouracil (5-FU), we investigated the gene expression levels of 5-FU metabolism-relating enzymes by real-time RT-PCR from FFPE samples and compared the results from FF samples in gastric and colorectal cancer. Methods: FFPE samples and FF samples were obtained from 46 patients with gastric cancer and 29 patients with colorectal cancer. Gene expression levels of tymidylate synthase (TS), OPRT, thymidine phosphorylase (TP) and DPD were determined by quantitative real-time RT-PCR. In FFPE samples tumor tissue was obtained using laser captured microdissection (LCM). Tumor sensitivity to 5-FU was evaluated by in vitro ATP assay. Results: Gene expression levels of TS, TP, DPD determined from FFPE samples significantly correlated with those from FF samples. Although respective gene expression levels alone failed to show signifcianct correlation with the in vitro 5-FU sensitivity, statistically significant correlation was noted either from the samples of FF or FFPE in both gastric (FF: r = 0.660, FFPE: r = 0.780) and colorectal cancer (FF: r = 0.780, FFPE: r = 0.660), when OPRT/DPD mRNA ratio was applied for comparison with the results of 5-FU sensitivity. Thus, high OPRT/DPD ratio determined from FFPE samples resulted in high sensitivity to 5-FU. Conclusions: From these results, it is suggested that sensitivity to 5-FU is predictable by quantitative RT-PCR using FFPE samples. Measurement of 5-FU metabolism-relating enzyme gene expression level from FFPE samples appeared to be feasible for predicting 5-FU sensitivity and to have great advantage to apply the molecular predicting assay in clinical settings. [Table: see text]
Sequence specificity of docetaxel (Doc) and the proteasome inhibitor PS-341 combinations in androgen-independent (AI) prostate cancer (CaP)
Authors: Holland W. S. , Lara P. N. , Kimura T. , Kenosi T. , Gandara D. R. , Devere White R. W. , Gumerlock P. H. 
Published: March 2020

13150 Background: AI CaP is an invariably fatal disease. While treatment with Doc, a microtubule-stabilizing taxane, improves survival, patient outcomes remain suboptimal. PS-341 inhibits degradation of cell cycle and tumor suppressor proteins resulting in cycle arrest and apoptosis. We hypothesized that the combination of Doc with PS-341 would abrogate the abnormal survival response seen in AI CaP and lead to improved tumor cell kill, but that results would be dependent on administration schedule due to interactive cell cycle kinetics. Methods: The PC3 cell line model of AI CaP was evaluated in vitro and in vivo to determine response to Doc or PS-341 alone, and in combination in sequences of PS-341→Doc, Doc→PS-341, and simultaneous (PS-341 + Doc). Cell cycle and protein analyses were performed by flow cytometry and Western blotting, respectively. For nu/nu mouse xenografts, 5 × 106 cells were injected subcutaneously into each flank. The agents were administered either together or 24hr apart, with all regimens given weekly [IP doses: Doc: 10 mg/kg; PS-341: 0.5 mg/kg]. Results: in vitro: Each combination showed an increased apoptotic sub-G1 population versus untreated cells, in addition to altered cell cycling in a sequence-specific manner. Of the combinations, PS-341 + Doc showed the largest sub-G1 while Doc→PS-341 had the lowest sub-G1 but the largest S-phase content; in vivo: PS-341 + Doc showed a cytotoxic effect (reduction in tumor volume) while the combinations of Doc→PS-341 and PS-341→Doc both showed growth inhibition (stabilization of tumor growth) as best response. Conclusions: Combinations of PS-341 and Doc have sequence specific cell cycle effects leading to increases in apoptosis (PS-341 + Doc) or cell cycle arrest (Doc→PS-341). Clinical validation of these findings is warranted. (ACS: CRTG-0019701-CCE) No significant financial relationships to disclose.
Radiotherapy plus concurrent irinotecan (CPT-11) and capecitabine (CAP) as preoperative downstaging treatment for locally advanced inoperable rectal cancer: A phase I/II study
Authors: Gollins S. W. , Myint S. , Levine E. , Bishop J. , Haylock B. , Susnerwala S. , Saunders M. , Biswas A. 
Published: March 2020

13519 Background: Preoperative downstaging chemoradiation has become standard treatment for locally advanced unresectable rectal cancer. Oral CAP is potentially more convenient as a radiation sensitiser than infusional fluoropyrimidine regimes. This study evaluated the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD) of daily CAP plus weekly i.v. CPT-11 when used in combination with RT in locally advanced rectal cancer. Methods: Patients had an adenocarcinoma of the rectum (lower limit within 12 cm of the anal verge) which on MRI was T3 within 2 mm of the mesorectal outer edge, T4, or any T3 within 5 cm of the anal verge. There were no distant metastases on staging investigations. Patients received planned pelvic RT to 45 Gy in 25 daily fractions over five weeks, concurrent with oral CAP daily throughout RT (including weekends) and a 60 minute infusion of i.v. CPT-11 weeks 1, 2, 3 and 4. Doses of CAP and CPT-11 were gradually escalated in cohorts of three patients. Results: The most common DLT was diarrhoea. Initially dose level (D/L) 3 was chosen as the recommended dose for phase II. However, unacceptable toxicity was encountered in the first 12 patients treated at D/L 3 (see Table). Thus D/L 2 is now being expanded to 60 patients for phase II. 40 patients have thus far potentially been eligible for resection: 5 (13%) could not be resected (2 deteriorated, 2 developed metastases, 1 died during treatment), 32 (80%) had R0 and 3 (7%) R1 resection. 9 (25%) had a pathological complete response (pCR) and 7 (20%) ‘near’ pCR. 5 (9%) of 57 patients had a defunctioning stoma pre-RT. Conclusions: The RD for this regime is 60 mg/m2 i.v. CPT-11 weeks 1, 2, 3, 4 and 650 mg/m2 bd of oral CAP daily. This demonstrates promising signs of efficacy. The RD is currently being studied in an expanded phase II cohort of 60 patients. D=diarrhea; F=febrile neutropenia; A=anorexia; L=lethargy; N=nausea/vomiting. [Table: see text] No significant financial relationships to disclose.
The therapeutic effect of radiofrequency ablation(RFA) combining with/without chemotherapy in treating inoperable liver metastases of colorectal cancers
Authors: Pan H. , Wang S. , Zheng Y. , Jin W. 
Published: March 2020

13581 Background: Patients (pts) with colorectal cancer often develop metastases to the liver without extra hepatic spread. Surgery is the mainstay of treatment in these pts, but only 20% of pts are suitable for a surgical approach and some pts are reluctant to receive surgery. This study is to compare the therapeutic effect of RFA combining with chemotherapy and RFA alone in treating inoperable liver metastases of colorectal cancers. Methods: From May 2001 to July 2005, 26 patients have inoperable liver metastases derived from colorectal cancer whose primary tumors were resected. Among them, 14 pts received chemotherapy from 3 months before RFA to 3 months after RFA (13 pts received systemic chemotherapy with FOLFOX4, 1 pt received FOLFIRI), 12 pts didn’t receive any chemotherapy. The metastatic lesions in liver were evaluated by CT scan every 3 months. Results: Pts’ characteristics: m/f 18/8; median age 57 yrs (range, 31–68); primary tumor: colon 15, rectum 11; karnofsky’s score≥60. Median no. of LM: 2.2 (range, 1–7), mean size of LM: 24mm (range, 12–97 mm). The last time of follow-up visit is Nov 2005, 11 pts has been dead because of tumor progression, 14 pts is still living, and 1 patient is lost to follow-up. The main complication of RFA is fever, local pain and elevation of hepatic enzyme. Reactive pleural effusion occurred in 1 patient which disappeared after thoracentesis. No RFA related bleeding,pneumathorax,perforation of digestive tract,infection and needle track implantation occurred. The median survival,1-year survival rates and 2-year survival rates in all pts were 33 months, 83.8% and 64.1% respectively. The median time to local progression in all pts is 346 days. In the pts treated with RFA alone, the median survival,1-year survival rates and 2-year survival rates were 18 months, 71.3% and 38.2% respectively; in the pts treated with RFA and chemotherapy, they were 36.5 months, 92.9% and 85.1% respectively (P=0.0210). In the pts treated with RFA alone, the median time to local progression is 346 days; in the pts treated with RFA and chemotherapy, it is 317 days (P>0.05). Conclusions: RFA Combining with chemotherapy is safe and may be more effective than RFA alone in treating inoperable liver metastases of colorectal cancer. No significant financial relationships to disclose.
Expression of thymidylate synthase in primary colorectal carcinoma and their corresponding metastases
Authors: Bendardaf R. , Elzagheld A. , Ristamäki R. , Syrjänen K. , Pyrhonen S. 
Published: March 2020

13587 Objective: Thymidylate synthase (TS) is the rate-limiting enzyme in the synthesis of pyrimidine nucleotides required for DNA synthesis and is a critical target for fluoropyrimidines, which are widely used in the treatment of gastrointestinal tumours. Tumour TS expression was analysed in a series of 39 patients diagnosed and treated for Duke’s B, C and D colorectal cancer between January 1996 and August 2003 to investigate the role of TS in the development of metastatic phenotype in CRC. Methods: TS expression was determined immunohistochemically in 39 paraffin-embedded primary and metastatic tumour sections and the overall staining index was calculated according to the intensity of the cytoplasmic staining (0, 1, 2, 3) and the fraction of the corresponding tumour cells in the sample. Results: Tumours were classified as showing either lower or higher TS expression, i.e. below- or above the mean. In 29/39 (74.3%) pairs, the primary tumours and their metastases are concordant. In 10 out of 39 (25.7%) discordant pairs, TS expression was high in the primary tumours and low in the metastasis in 9/10 cases, and opposite in the remaining one case. Using the absolute staining index values, TS expression in the primary tumours and in the metastases was also significantly correlated (Pearson R=0.501, p=0.001). Conclusion: Between the paired primary tumours and distant metastatic lesion, the TS expression is in the majority higher in primary tumours compared to the metastasis and more concordant cases showed compared to discordant cases and in 9/10 discordant cases, TS expression in the primary tumours was above the mean and below the mean in their corresponding metastases compare to only one case showing the opposite pattern. No significant financial relationships to disclose.