bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of bone loss in breast cancer patients: 24-month results from the ARBI trial of anastrozole with risedronate
Authors: Markopoulos C. , Tzorakoleftherakis E. , Polychronis A. , Venizelos V. , Xepapadakis G. , Kalogerakos K. , Papadiamantis J. , Zobolas V. , Janinis J. , Dafni U. 
Published: August 2020

552 Background: The management of bone mineral density (BMD) in postmenopausal, breast cancer (BC) patients (pts) receiveing anastrozole was investigated in this phase III, multicenter, open label trial. Methods: Pretreatment BMD of 217 eligible pts with hormone receptor-positive BC scheduled to receive anastrozole was evaluated at lumbar spine (LS) and hip (HP). Pts with T-score<-2.0 in LS or HP, received anastrozole 1mg/day plus oral risedronate 35 mg/week (A+R) and pts with T-score>-1 in both sites received anastrozole only (A). Pts with T-score<-1 in either site but T-score>-2.0 in both sites were randomized to receive A+R or A alone. All pts received Calcium and Vit D daily. BMD was then assessed at 12 and 24 months. Results: Comparison of randomized arms (A = 33 pts, A+R = 37 pts): T-score change from baseline was significantly different only for LS at 24 months (-0.23 in A vs 0.41 in A+R, Wilcoxon test p = 0.007) and was significantly higher from baseline for the A+R arm (Signed rank test p = 0.01). At 12 months, among A only pts, 4 (12.1%) had a T-score<-2.0 without becoming osteoporotic, while 2(6.1%) moved to the normal BMD region; from A+R pts, only 2(5.4%) had a T-score<-2.0 without becoming osteoporotic, while 9 (24.3%) moved to the normal BMD region. The same trend in BMD changes was also observed at the 24 month evaluation. Group with T-score<-2.0 in either LS or HP (A+R, n = 99): a significant increase for LS both at 12 and 24 months was detected (median increase of T-score by 0.45 and 0.37, p<0.01 for both time points) with a corresponding non-significant change in HP (p = 0.91 and p = 0.15). BMD in 13(13.3%) pts improved to the osteopenic region (-2.0<T-score<-1.0). Group with T-score>-1 in both sites (A, n = 48): significant decrease was detected for HP and LS, both at 12 and 24 months; however, only 11 (22%) pts became osteopenic and 1(2%) became osteoporotic. Conclusions: The addition of oral risedronate in postmenopausal BC patients with osteopenia receiving anastrozole has a favourable effect in BMD at lumbar spine at 24 months. [Table: see text]
Phase II evaluation of cisplatin plus cetuximab in the treatment of recurrent and persistent cancers of the cervix: A limited access phase II study of the Gynecologic Oncology Group
Authors: Farley J. H. , Sill M. , Walker J. L. , Schilder R. J. , Thigpen J. T. , Coleman R. L. , Miller B. E. 
Published: August 2020

5521 Background: A majority of cervical cancer patients overexpress epidermal growth factor receptor (EGFR), which is a poor prognostic factor. Cetuximab (C225) is a murine monoclonal antibody that binds to EGFR and competes with ligand binding and tyrosine kinase activation.Given the evidence of activity in squamous carcinomas of the head and neck, the purpose of this study was to evaluate the safety and efficacy of cisplatin and cetuximab chemotherapy. Methods: Women with advanced, persistent, or recurrent carcinoma of the cervix not amenable to cure were eligible for this study. Only prior chemotherapy (CT) administered in conjunction with primary radiation as a radiosensitizer was allowed. Women could not have received prior anti-EGFR antibody therapy or therapy with a tyrosine kinase inhibitor that targets the EGFR pathway. All women had measurable disease and a GOG performance status ≤ 2. The women received cisplatin at 30 mg/m2 days 1 and 8. The first dose of C225 was given at 400 mg/m2. All subsequent doses of C225 were given at 250 mg/m2. C225 was given on days 1, 8, and 15. Each cycle was 21 days. Adverse events were assessed with CTCAE v 3.0. Primary measure of clinical efficacy was the frequency of tumor response. The study was stratified by prior CT. The design required at least 16 responses in a sample of 40 with prior CT and 29 without prior CT before the regimen was considered for phase III testing. Results: Between September 2004 and March 2008, 76 patients were entered onto the study. Of these, 69 were eligible and evaluable. Three patients were on study at the time of the analysis. 56 (81%) patients had received prior radiation. 40 (58%) patients previously received prior CT. There were 8 (12%) responses. The response rate was 8% among patients with prior CT, and 17% among CT naïve patients. One woman had grade 4 anemia. The most common grade 3 toxicities were metabolic (14), dermatologic (8), fatigue (6), and gastrointestinal (6). Conclusions: The combination of cetuximab with cisplatin was adequately tolerated but did not indicate additional benefit beyond cisplatin therapy. Stratification of patients based upon K-ras mutation and/or EGFR status may select a group for which this regimen is most effective. No significant financial relationships to disclose.
What do patients think about CA-125 monitoring in the follow-up? Results from a multicenter trial in 1,060 patients with ovarian cancer
Authors: Oskay-Oezcelik G. , du Bois A. , Fasching P. A. , Mahner S. , Liebrich C. , Glaβ A. , Schmidt-Wetze S. , Sepp L. , Münstedt K. , Lichtenegger W. , Sehouli J. 
Published: August 2020

5522 Background: In the clinical day CA-125 monitoring is frequently used as a part of follow-up care for patients with ovarian cancer (OC). However, the potential benefit of CA-125 controls in the absence clinical symptoms are still unclear.There is little known about the expectations and preferences of patients with OC. Therefore we have initiated a multi-institutional survey. Methods: A semi-structered consisting 15 questions was developed in a pilot-study of 20 patients. After this validation all gynecological departments and gynecological-oncological practices were invited to participate in this trial using an anonynomous print version of the questionaire Results: Between December 2006 and December 2007 a total of 1,060 patients were enrolled. The median age of the patients was 58 years (range 16–87). 60% of the patients had primary ovarian cancer, 40% had relapsed ovarian cancer. Routine follow-up visits were mostly performed by gynaecologists in a gynaecological practice (56.9%) and in hospitals (49.5%). Patients were informed about the procedures and goals of cancer care predominantly after primary surgery (62.5%) and in 15.7% after last cycle of first-line chemotherapy. 7.7% declared that they were informed only at the first follow-up visit, 9.2% stated that they have never received any information about their cancer care management. According the patient´s opinion the main objective for the follow-up is the early detection of relapse and a prolongation of overall survival (95.8%). About more than 90% get CA-125 measurements. These were the procedures with highest anxiety but also the most important procedure for the patient. Finally, most patients (89%) were satisfied from their management of cancer care. Conclusions: The present study is the largest survey about cancer care so far and provides several important data for physician-patient communication concerning the follow-up management of patients OC. No significant financial relationships to disclose.
Tissue levels of cisplatin in previously traumatized tissue without adhesion formation in a rabbit sidewall adhesion and intraperitoneal delivery model
Authors: Awtrey C. S. , Greenawalt K. E. , Colt J. M. , Corazzini R. L. , Philbrook M. , Santos M. R. , Bristow R. E. 
Published: August 2020

5525 Background: It has been hypothesized that the presence of extensive adhesions after ovarian cancer resection may limit the distribution of intraperitoneal (IP) chemotherapeutics. The objective of this study was to determine if using a hyaluronate/carboxymethylcellulose (HA/CMC) barrier to prevent adhesions during a simulated tumor resection surgery would increase tissue drug levels following subsequent IP chemotherapy. Methods: A sidewall defect/cecal abrasion model was used to induce adhesion formation and simulate tumor resection trauma in 22 rabbits. Seven rabbits received HA/CMC at the end of the surgery. Four weeks after surgery, cisplatin (2.5mg/kg) was administered IP to HA/CMC treated and untreated animals or IV to untreated controls. Animals were sacrificed 24hrs after infusion and tissue samples were collected from inside the defect (with or without adhesions) and outside the defect on the contralateral sidewall. Samples were cryosectioned and analyzed for platinum content by ICP/MS. Results: Platinum tissue levels in the uppermost peritoneal layer (0–1mm) were significantly higher for IP delivery than IV and were the highest for IP delivery when no adhesions were present inside the defect. Platinum levels were significantly higher in the previously traumatized tissue inside the defect than in untraumatized tissue outside the defect. This was consistent for both IP or IV and HA/CMC treated or untreated animals. The benefit of HA/CMC was underscored by the fact that samples under adhesions could not be obtained for that group due to the significant reduction in adhesion formation compared to untreated controls. Conclusions: Recently traumatized tissue without adhesions had the highest platinum levels following IP cisplatin in this model. The previously traumatized tissue had significantly higher platinum levels than untraumatized tissue likely due to both increased peritoneal diffusion and systemic delivery components. [Table: see text] [Table: see text]
Randomized trial of intrapatient dose escalation of single agent carboplatin as first-line treatment for advanced ovarian cancer: An SGCTG study (SCOTROC 4)
Authors: Kaye S. B. , Vasey P. , Rustin G. , Pledge S. , Williams C. , Gabra H. , Skailes G. , Lamont A. , Lewsley L. , Paul J. ,   Scottish Gynaecological Cancer Trials Group
Published: August 2020

5537 Background: In the absence of toxicity, carboplatin (the most widely used drug in ovarian cancer) is generally given at the same (flat) dose with each treatment cycle. However, retrospective data suggest a correlation between extent of myelosuppression and outcome, as has been observed in other diseases. Our hypothesis was therefore that intrapatient dose escalation, according to nadir blood counts, could lead to an improved outcome compared to conventional flat dosing. Methods: Patients with previously untreated stage IC to IV ovarian cancer were randomized to receive 6 cycles of carboplatin AUC 6 q3 w either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2–6 based on nadir FBC (Arm B). The primary outcome measure was progression-free survival (PFS), and a target accrual of 1300 pts was envisaged, aimed at detecting a 20% increase in PFS with 80% power (5% 2-sided level of statistical significance). Results: From March 2004 to November 2008, 937 pts were recruited from 70 centres. Dose escalation occurred in 82% pts on Arm B. The median AUCs actually received were 6.0 (Arm A) and 6.84 (Arm B). As expected, more myelosuppression was seen in Arm B (p < 0.001 for all parameters). More grade 3/4 non-haematological toxicity was also seen in Arm B (31%, vs 22% in Arm A, p < 0.001) but there was no significant difference in global quality of life. To date, 477 PFS events have been observed out of a planned total of 950. The median PFS was 13.9m in Arm A, and 13.5m in Arm B, and the observed hazard ratio (Arm B/Arm A) is 1.04, with 95% C.I. of 0.87 to 1.24. This excludes the clinically relevant benefit of 0.83 used to design the study. A futility analysis also indicated that the probability of a statistically significant result in favour of Arm B at the planned study end was 0.12 at best. Conclusions: Following the Data Monitoring Committee recommendation, the trial has therefore been closed to recruitment, with no evidence of benefit for intra-patient dose escalation of carboplatin. A separate analysis of tissue samples, aimed at elucidating mechanisms of (single agent) carboplatin resistance is ongoing. No significant financial relationships to disclose.
Persistance of circulating tumor cells (CTCs) in peripheral blood of breast cancer (BC) patients two years after primary diagnosis
Authors: Rack B. K. , Schindlbeck C. , Schneeweiss A. , Schrader I. , Lorenz R. , Beckmann M. , Pantel K. , Lichtenegger W. , Sommer H. , Janni W. 
Published: August 2020

554 Background: In metastatic BC, CTCs have shown to predict treatment efficacy and reduced survival. Recent data also indicate a potential prognostic relevance of CTCs after adjuvant chemotherapy. The SUCCESS trial evaluates the role of persisting CTCs two years after diagnosis in primary BC patients treated with zoledronate. Methods: We analyzed 23 mL of peripheral blood in N+ and high-risk N- primary BC pts receiving 3xFEC(500/100/500)-3xDoc100 q3w vs. 3xFEC(500/100/500)-3xDocgemcitabine (75/1000 d1+8) chemotherapy followed by 2 yrs (4mg q3mx24m) vs. 5 yrs (4mg q3mx24m followed by q6mx36m) of zoledronate. CTC results after two years are shown. CTCs were assessed with the CellSearchSystem (Veridex, Warren, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labelled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies. Pts were examined after a mean of 29 months (range 20–43). Results: The data of 579 pts two years after diagnosis are available. 4.3% of pts (n = 25) presented with >1CTC in peripheral blood. In pts with the detection of CTCs, the mean number of cells was 1 (range 1–29). While we found 1 CTC in 5.9% and 2 CTCs in 1.6% of pts, 1.5% had 3–5 CTCs, 1.2% >5 CTCs. The presence of >1CTC did not correlate with tumor size (p = 0.41), nodal status (p = 0.41), grading (p = 0.45), hormonal status (p = 0.92) or HER-2-Status of the tumor (p = 0.59). In this patient group, 9.7% and 6.9% of pts had presented with >1CTC at primary diagnosis and after chemotherapy, respectively. While the presence of CTCs at diagnosis was associated with CTCs after two years (p = 0.03), there was no correlation of CTCs after chemotherapy with the results at primary diagnosis (p = 0.08) or at two years (p = 0.23). In 184 postmenopausal HR+ pts endocrine treatment data was analyzed. CTCs at two years were detected in 6.8% of pts on tamoxifen (n = 9), while 1.9% of pts were positive on anastrozole treatment (n = 1; p = 0.19). Conclusions: CTCs persisting cytostatic, endocrine and zoledronate treatment, can be observed in a relevant number of clinically recurrence-free BC patients. Longer follow-up within the German SUCCESS study will give further insight in their prognostic relevance and show whether they can be used for real time tumor phenotyping or serve as treatment target. [Table: see text]
Adding the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin in first line for stage IC-IV epithelial ovarian cancer: A randomized phase II study
Authors: Reyners A. , Smit W. M. , Schaapveld M. S. , Hoekman K. , Erdkamp F. , Lalisang R. , Graaf H. , Wymenga M. A. , Polee M. , Willemse P. H. 
Published: August 2020

5545 Background: Inhibition of COX-2 reduces the growth rate of tumors in vitro and COX-2 is over-expressed in ovarian cancer, so a COX-2 inhibitor might be beneficial. Methods: After debulking surgery patients (pts) with advanced epithelial ovarian cancer (FIGO IC-IV) received docetaxel 75 mg/m2 and carboplatin AUC=5 (CT) for 6–9 cycles q 3-wks and were randomized to celecoxib 400 mg BID (COX) for max three years or to control (CTR), stratified for residual tumor present in 58% vs 54%. Response rates and progression-free survival were based on CA-125 levels according to Rustin. Primary endpoints were biochemical CR (bCR)and safety, secondary progression free- (PFS) and overall survival (OS). Results: 183 of 201 pts enrolled were analyzed and baseline characteristics were well balanced between COX (n = 91) and control (CTR) arms (n = 93). Safety: Docetaxel and carboplatin was given full dose in 89% vs 84% pts and creatinine clearance remained stable vs baseline in both arms (96% vs 97% at Cycle 6). Toxicity grade 3–4 (COX vs CTR) was neutropenia in 26 vs 32, febrile neutropenia 12 vs 12, N/V 6 vs 5, allergy 7 vs 0 pts. Neurosensory grade 2–3 was less in COX (4 vs 13 pts, p< 0.05). Efficacy: Median duration of COX treatment was 6 months and 60% completed the combination with six or more cycles of CT. At a median follow-up of 20 months, CA-125 normalized (bCR) in COX 55/74 (74%) and CTR 49/74 (66%) pts with elevated baseline levels (n.s.). Median PFS was 17.4 vs 14.5 months (n.s.) and median survival 34.2 vs 34.7 months (n.s.). Conclusions: Celecoxib added to docetaxel/carboplatin in epithelial ovarian cancer had no effect on creatinine clearance, CA-125 response, PFS or OS. Celecoxib during CT was associated with allergic skin reactions but less neurotoxicity. No significant financial relationships to disclose.
Plasma levels of estrone sulfate (ES) in postmenopausal women with breast cancer (BC) during letrozole (L) treatment: Association with single nucleotide polymorphisms (SNPs) of CYP19A1
Authors: Lunardi G. , Del Mastro L. , Serra M. , Driol P. , Boni C. , Cognetti F. , Ponzone R. , Porpiglia M. , Venturini M. , Pronzato P. 
Published: August 2020

555 Background: The CYP19A1 gene encodes aromatase, a key enzyme for estrogen biosynthesis. We investigated the association between four CYP19A1 SNPs, affecting different circulating estrogen levels (rs10046 C>T, rs4646 G>T, rs749292 C>T, rs727479 T>G), and suppression of plasma ES levels induced by 6 weeks (time needed to reach L steady-state concentrations) of L (25 mg/d). Methods: Patients were enrolled into a prospective, italian multi-centre trial (GIM5) testing the correlation of CYP19A1 SNPs with the efficacy of L adjuvant therapy, after 5 years of tamoxifen, in postmenopausal early BC patients. Blood samples for hormone measurements were obtained immediately before starting L (baseline) and following 6 wks of treatment. SNPs were identified from DNA obtained from peripheral blood cells by Hexaprimer Amplification Refractory Mutation System PCR (H-ARMS-PCR). Plasma ES levels were evaluated by Radio Immuno Assay (RIA). Results: SNPs and hormone levels were evaluated in at least 129 patients. SNPs of CYP19A1 were associated with different baseline plasma ES levels. Mean inhibition of aromatase activity induced by L ranges from 71% to 79%, as a function of the SNPs. After 6 weeks of L no difference in ES levels was observed between patients with different SNPs (Table). Conclusions: L therapy induces a higher aromatase suppression in patients with SNPs associated with higher baseline plasma ES levels. The difference in ES levels associated with genetic variation at the CYP19A1 locus disappeared after L therapy. [Table: see text] [Table: see text]
Eribulin mesylate (halichondrin B Analog E7389) in platinum-resistant epithelial ovarian cancer (PR-EOC): A CTEP-sponsored phase II study
Authors: Hensley M. L. , Kravetz S. , Sima C. , Tew W. , Pereira L. , Sabbatini P. , Whalen C. , Aghajanian C. A. , Zarwan C. , Berlin S. 
Published: August 2020

5561 Background: Eribulin mesylate is a tubulin inhibitor whose mechanism of action differs from that of other anti-tubulin agents, suppressing microtubule growth without affecting depolymerization, and sequestering tubulin into non-functional aggregates. In NIH:OVCAR-3 human EOC xenograft models, eribulin increased survival and reduced size and number of metastases, with activity superior to paclitaxel. We sought to determine the frequency of objective response to treatment with eribulin in patients (pts) with PR-EOC. Methods: Pts with PR-EOC, fallopian tube or peritoneal cancer (progression-free interval from last platinum-based therapy < 6 months), measurable disease, < 2 prior cytotoxic regimens, ECOG performance status 0–1, and adequate organ function were eligible. Treatment: eribulin 1.4 mg/m2 over 15 minutes IV days 1 and 8, every 21 days. Response assessed by CT for RECIST every other cycle. Results: 36 pts (median age 61, range 38–80; median platinum-free interval 3 months, range 0.1–5.9; all having received platinum-taxane first-line treatment) enrolled. 35 are evaluable for response (1 pt off-study for unrelated myocardial infarction in cycle 1). Two pts achieved partial responses (PR-5.7%), with response durations of 84 days and 128 days. Time to PR was 2.8 months in both. >50% decrease in CA125 for more than two measurements was observed in 3/31 CA125-evaluable pts. 16/35 (46%) had stable disease as best response. Median progression-free survival was 2 months (range 1–7 months). Per patient, at least possibly-related grade 3–4 toxicities were: neutropenia 44%, leucopenia 31%, anemia 3%, lymphopenia 3%, febrile neutropenia 3%, muscle weakness 3%, hypophosphatemia 3%, hypokalemia 6%, infection 6%, thrombosis 6%. Conclusions: Eribulin has minimal activity in PR-EOC with objective response observed in only 5.7% of pts. Time to objective response was nearly 3 months. Median PFS was 2 months. Activity of eribulin in platinum-sensitive patients is being studied in a separate phase II cohort. [Table: see text]
Performance of a biomarker panel to identify malignancy within a pelvic mass population
Authors: Chen L. , Homesley H. D. , Scribner D. R. , Cantuaria G. H. , He Q. , Cheek R. L. , Whitehead C. M. , Doobay H. , Fischer T. J. 
Published: August 2020

5566 Background: We previously reported the performance of biomarker combinations that displayed utility in identifying ovarian cancer from normal sera and in monitoring for disease recurrence. In this study, we evaluated the performance of a subset of these markers in differentiating ovarian cancer from benign pelvic mass. Methods: Pre-operative serum samples were prospectively collected from 254 patients undergoing surgical evaluation for differential diagnosis of a pelvic mass. Pathology showed 76 cases of epithelial ovarian carcinoma (EOC), 17 borderline tumors, 11 other gynecologic cancers, and 150 benign masses. 18 (23.7%) of the EOC patients had stage I tumors; 6 (7.9%) stage II; 44 (57.9%) stage III; and 8 (10.5%) stage IV. Serum levels of CA125, HE4, glycodelin, SLPI, MMP7, and Plau-R were ascertained. Biomarker performance was evaluated by a logistic regression model and leave one out cross-validation analysis. All calculations compared the benign vs. EOC and borderline tumor populations. Results: Individual biomarker sensitivity ranged from 28% to 77% at 85% specificity. The combination of CA125, HE4 and glycodelin exhibited the highest overall performance in identifying malignancy from benign masses, demonstrating 80% sensitivity, 80% specificity in patients <55 years, and 89% sensitivity, 80% specificity in patients ≥55. Total cohort performance was 85% sensitivity and 80% specificity. Glycodelin identified 7/22 CA125 and HE4 double negative patients, 5/7 of these patients were early stage (borderline, I or II), while only adding 4/150 false positive cases. Conclusions: Biomarker analysis within this test cohort demonstrates potential clinical utility in the differential diagnosis of pelvic mass patients, especially for the detection of early stage disease. The addition of glycodelin improved the detection of early stage cancer in sera that were negative for both HE4 and CA125. [Table: see text]