bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between Mad1 G558A and ERCC1 C8092A polymorphisms and response to induction chemotherapy in advanced ovarian carcinoma
Authors: Figueroa P. , Castro Hernández C. , Santibáñez Andrade M. , Díaz Romero M. , Morales Vázquez F. , Gallardo Rincón D. , Herrera Montalvo L. A. 
Published: August 2020

5568 Background: Platinum and taxane remain active drugs in the treatment of ovarian cancer.The polymorphism C8092A of ERCC1 is involved in NER pathway of platinum induced damage DNA and Mad1 G558A with modulation of the chromosomal segregation. As primary aim we evaluated the influence of these polymorphisms in the chemotherapy response. Methods: ERCC1 C8092A and Mad1 G558A polymorphism allelic and genotypic frequency was determined on DNA isolated from blood tumor samples by PCR and specific digestion in 56 patients with cancer of advanced ovary who received induction chemotherapy with 3 courses of paclitaxel 175 mg/m2 and AUC6 carboplatin every 3 weeks. Informed consent was obtained for all subjects and the study was approved by the hospital ethic committee. Results: Between January 2008 to June 2008, 56 women were evaluated, with age media was 53 years, majority characteristics were stages III (66.9%) 37 and IV (33.1%) 19 patients, histology serous papillary (94.6%) high-grade differenced (73.2%). Mad1 genotype were 7 G/G (12.5%), 30 were G/A (53.6%), 19 were A/A( 33.9%), and ERCC1 genotype were 20 C/C (35.7%), 30 were C/A (53.6%) and 6 were A/A (10.7%). All biochemical response by Rustin criteria was noted in 89.28%. Allele A for Mad1 is more frequently observed in patients with ovarian carcinoma versus in mexican healthy women (61% vs. 49%) and suggests the possibility that the polymorphism of Mad1 is a marker of risk for ovary cancer (RR = 1, 15, p < 0, 05). According our aim we observed a higher response in allele G (91.89%) than allele A (87.75%) of Mad1 (p < 0.10).Interestingly allele A of ERRC1 was not associated greater response (88.88% vs. 92%, p > 0.10). Additionally we evaluated the predictive value of Ca 125 return to normal range after 3 chemotherapy courses, showed in 22 patients (39.28%) in univariate analysis we noted that allele G of Mad1 has been linked to improved response (p = 0.041). Conclusions: This is the first study in ovary cancer that evaluates predictive value of two SNP, one of them involved in the spindle checkpoint and the other in DNA repair mechanism (NER), suggesting to Mad1 G558A likely risk polymorphism for ovary cancer and response to chemotherapy based on taxanes, which may be a predictive biomarker. No significant financial relationships to disclose.
Paclitaxel, ifosfamide, and cisplatin regimen as neoadjuvant chemotherapy in young women with locally advanced squamous cervical cancer
Authors: Marinaccio M. , De Marino E. , Mele E. , Catacchio R. , Pellegrino C. , Pinto V. , Schonauer S. 
Published: August 2020

5587 Background: Chemoradiotherapy is the standard treatment of advanced cervical cancer. Neoadjuvant chemotherapy (NAC) may represent an alternative for locally advanced cervical cancer (LACC).This study was undertaken to evaluate the efficacy of NAC in young patients with squamous LACC. Methods: Since 2000 to 2008, 61 pts (mean age 43 yrs) with squamous LACC were treated with NAC and afterwards evaluated for radical surgery. Eligibility included proven histologically diagnosis of squamous cervical carcinoma, FIGO stage IB2/IIA>4cm/IIB, measurable disease, ECOG PS 0–2, no prior therapy and age under 49 years. All patients received TIP regimen (cisplatin 50 mg/m2 i.v. day 1, paclitaxel 175 mg/m2 over 3 hrs i.v.day1, ifosfamide 5,000 mg/m2 plus mesna 6,000 mg/m2 over 24 hrs i.v. day 1–2). Each cycle was repeated every 21 days. Patients were evaluated 4–6 weeks after the completion of the third cycle with the purpose to perform radical surgery according to clinical response. Results: 35pts (57.4%) were stage IB2; 9 (14.7%) were IIA >4cm; and 17 (27.9%) were IIB. After restaging the clinical results were: CR = 4/61 (6.6%), PR = 51/61 (83.6%); no response = 5/61 (8.2%); progression = 1/61 (1.6%). A total of 55 pts (90.1%) were eligible for surgery; 6/61 pts (9.8%) were submitted to curative radiotherapy (until 2004) or chemoradiotherapy. Pathological responses after surgery were: 4 pCR (7.3%); 46 pPR (83.6%); and 5 (9.1%) pPR with presence of positive surgical margins or metastatic lymph nodes. Out of 55 pts, 50 received 2 cycles of TIP regimen as a consolidation therapy before follow-up; 5 pts with incomplete pPR underwent radio/chemoradiotherapy. After NAC an overall downstaging of LACC was obtained in 50/61 pts (82.0%). In this group of pts at the median follow-up of 42 months (range 4–98) updated as of December 2008, the 3-years progression-free survival and overall survival are 85.9% and 82.0%, respectively. Conclusions: Our results indicate that TIP regimen-based NAC is an attractive option in young women with squamous LACC (IB2,IIA >4cm, IIB) that strongly desire surgery.The rate of patients with a prolonged remission of disease (82.0%) suggests that the clinical benefit of TIP regimen-based NAC followed by surgery may be comparable to chemoradiotherapy. No significant financial relationships to disclose.
A phase II study of aflibercept (VEGF trap) in recurrent or metastatic gynecologic soft-tissue sarcomas: A study of the Princess Margaret Hospital Phase II Consortium
Authors: Townsley C. , Hirte H. , Hoskins P. , Buckanovich R. , Mackay H. , Welch S. , Wang L. , Polintan R. , Chen A. , Oza A. M. 
Published: August 2020

5591 Background: Targeting angiogenesis and vascular endothelial growth factor (VEGF) represents a promising approach to treat highly vascular tumors, like gynecologic sarcomas. Aflibercept, a long-acting inhibitor of VEGF signaling, potently binds and inactivates VEGF, thus blocking tumor angiogenesis and growth. Methods: This is a single-arm, open-label, two-stage phase II clinical trial designed to evaluate the efficacy and toxicity of aflibercept as treatment for patients (pts) with recurrent, or metastatic gynecologic soft tissue sarcoma. Aflibercept was administered at 4 mg/kg IV every 2 weeks and pts had radiologic imaging performed every 8 weeks. The primary endpoints were response rate and prolonged stable disease. Results: Twenty-five pts with leiomyosarcoma of the uterus and 13 pts with carcinosarcoma of the uterus were enrolled in 2 cohorts. In the leiomyosarcoma group, 24/25 pts had an ECOG of <1, most pts (22/25) had <1 previous lines of treatment and 7/25 pts had prior radiotherapy. A total of 149 cycles were administered for this group, with a median of 4 (range 2–28). In the carcinosarcoma group, 10/13 pts had an ECOG of <1, most pts (12/13) had <1 previous lines of treatment and 5/13 pts had prior radiotherapy. A total of 31 cycles were administered with a median of 3 (range 1–4). The most frequent adverse events experienced by all pts, of any grade, were fatigue 71% pts, constipation 53% and hypertension 39% . The most frequent grade 3 or higher, adverse events were hypertension 18%, fatigue 13% and lymphopenia 8%. Eight pts with leiomyosarcoma had stable disease (4pts > 6 mo). No reponses were seen in either cohort and no stable disease was seen in the carcinosarcoma group. Median overall survival was 15.1 mo (95% CI: 8.5 - not reached) for the leiomyosarcoma cohort and 3.1 mo for the carcinosarcoma cohort (95% CI: 1.9 - not reached). The requirements to proceed to stage 2, in leiomyosarcoma, were met after more than 2/21 patients had > 6 mo PFS. Carcinosarcoma cohort has not finished stage 1 and both cohorts continue accrual. Conclusions: VEGF-trap was well tolerated in this pt population with acceptable side effects. Initial efficacy data suggests modest activity, particularly in patients with leiomyosarcoma. [Table: see text]
Evaluation of the protective effects of zoledronic acid on bone mass in premenopausal women undergoing adjuvant chemotherapy following treatment discontinuation
Authors: Hershman D. L. , McMahon D. , Crew K. D. , Shao T. , Cremers S. , Brafman L. , Awad D. , Shane E. 
Published: August 2020

562 Background: Adjuvant chemotherapy is associated with a significant reduction in bone mineral density (BMD) in premenopausal women with breast cancer (BC). We previously showed that this loss of BMD can be prevented with zoledronic acid (ZA) every 3 months for a year. Since bone loss in women with osteoporosis is prevented with annual ZA, we examined whether protection from bone loss by ZA in women with BC persists following discontinuation of ZA. Methods: A randomized, double-blind, multicenter, phase III trial comparing ZA (4 mg every 3 months) versus placebo for 1 year in premenopausal women with BC undergoing adjuvant chemotherapy was conducted. Patients had serial BMD measurement at 0 (after surgery and before chemotherapy), 6, 12 and 24 months. Demographic, clinical, and tumor characteristics were collected. Serum was stored at -70°C and analyzed in batches. The secondary outcome of percent change in BMD at 24 months, one year following the last ZA/placebo, is presented. Intention-to-treat analyses with linear mixed models were performed using SAS version 9. Results: Of 101 patients randomized, 85 completed 12 month, and 62 completed 24 month evaluations; mean age 41 (SD 5.2). Demographic and baseline characteristics were similar between treatment groups. By 24 months, 38 (61%) had not regained their menses; 22 patients were on tamoxifen, 25 were on an aromatase inhibitor. Chemotherapy without ZA was associated with a significant decline from baseline in lumbar spine (LS) BMD after both 12 (-5.4%) and 24 (-6.3%) months. Similarly total hip (TH) and femoral neck (FN) BMD declined by 2.6% and 2.4% by 24 months, respectively. In contrast, BMD remained stable in ZA-treated patients (p < 0.0001 vs placebo). Patients who received ZA had stable BMD at 24 months (LS -0.58%, TH 0.83%, FN 0.04%). Analysis of bone turnover markers is ongoing. Conclusions: Premenopausal women receiving adjuvant chemotherapy for BC had significant bone loss in the first year that persisted in the second year. ZA every 3 months for a year effectively prevented bone loss during the first year and 1 year after completion of ZA treatment. One year of ZA maintains BMD in premenopausal BC patients for an additional year after discontinuation of ZA. [Table: see text]
Randomized phase II study of neoadjuvant chemotherapy and trastuzumab for operable breast cancer with overexpression of HER2
Authors: Masuda N. , Ando M. , Aogi K. , Ino H. , Iwata H. , Tokuda Y. , Nakamura S. , Yamamoto N. , Fujiwara Y. 
Published: August 2020

565 Background: Achievement of pathological complete response (pCR) by primary systemic therapy (PST) correlates with improved survival in operable breast cancer patients. Based on data of the higher pCR rate with concomitant chemotherapy and trastuzumab (H) reported by some clinical trials, we performed a multi-center, prospective randomized phase II study to evaluate the efficacy of adding H to standard chemotherapy and to determine more effective agent which will show higher pCR by the comparison between weekly paclitaxel (P) and tri-weekly docetaxel (D) in neo-adjuvant setting for HER-2+ pts. Methods: Generally, the concomitant combination with anthracycline and H is not recommended because of the increasing cardiac toxicity. PST regimen was scheduled as the sequential chemotherapy with 4 cycles of CEF (cyclophosphamide, epirubicin 100 mg/m2, 5FU) followed by 4 cycles of q3w H with qw P 80 mg/m2 (HP) or q3w D 75 mg/m2 (HD). The primary objective was designed to evaluate the pCR, defined as no evidence of residual invasive cancer in axilla and breast. The inclusion criteria was pts with Stage II or IIIA, HER-2 overexpression, under 65-yo, adequate cardiac function (EF>=60%) and a written informed consent. The sample size was estimated to detect the difference of pCR rate >=10% from 30% baseline, as at least 100 pts. The pathological response was evaluated by central review. Results: From March 2007 to June 2008, 102 pts were enrolled and randomized as well balance in the same number, median age (51yo), and the same distribution of clinical stage. 88 pts (86%) was successful on complete treatment course. Pre-matured data was available for 60 pts whom central review had been completed: there was no significantly difference in pCR rate between two groups, 53% (95%CI: 35.4–71.1%) on HP and 47% (28.8–64.5%) on HD. Out of 30 pts with pCR, 13 pts had component of DCIS. Serious adverse events were reported on 13 cases; mainly febrile neutropenia was experienced on 6 pts. One after the HP course had experienced the cardiac failure to fall in LVEF to 39%. Conclusions: In HER-2+ pts, PST with CEF followed by HP or HD might be equally active and achieving high pCR without significant toxicity. The final reviewed results will be established until May 2009, and presented at the ASCO meeting. No significant financial relationships to disclose.
Gain study: A phase III trial to compare ETC versus EC-TX and ibandronate versus observation in patients with node-positive primary breast cancer
Authors: Möbus V. , Conrad B. , Schneeweis A. , Kreienberg R. , Solomayer E. F. , Clemens M. R. , Tesch H. , Loibl S. , Nekljudova V. , von Minckwitz G. 
Published: August 2020

568 Background: Möbus et al. showed that dd epirubicin (E), paclitaxel (T), cyclophosphamide (C) results in a superior DFS compared to conventionally dosed EC-T in pts with primary breast cancer (PBC) and ≥3 involved lymph nodes (LN). In this study, the dd, dose intensified strategy has been further investigated as well as the use of ibandronate (I) adjuvant and ESF. Methods: A prospective, multi-center, controlled, non-blinded, randomized phase III trial investigating ETC (E: 150 mg/m2, T: 225 mg/m2, C: 2,000 mg/m2, i.v. day 1, q15 for 3 cycles each: A1; or EC→TX (E: 112.5 mg/m2 + C: 600 mg/m2, i.v. day 1 q 15 for 4 cycles → T: 67.5 mg/m2 i.v. day 1, q 8 for 10 weeks + X: 2000 mg/m2 p. o. day 1–14, q 22 for 4 cycles: A2). Pts were further randomized in a 2:1 ratio to receive I: 50 mg/day p.o. for 2 years (B1) or observation (B2). Pts received a primary prophylaxis with either epoetin β or darbepoetin α and during ETC/EC with pegfilgrastim. After recruitment of 1500 pts prophylactic ciprofloxacin was implemented. Eligible: Females ≥18 and <65 years, histologically confirmed LN positive uni- or bilateral PBC; adequate surgery, ≥1 pos. LN out of ≥ 10; no previous/concurrent therapy; ECOG ≤2; written informed consent. Primary objective: compare DFS A1 vs. A2 and B1 vs. B2. Secondary objectives: OS, safety, incidence of secondary primaries, and EFS in subgroups of hormone sensitivity and pos. LN between arms; assessment of compliance and responders to ESF; determine prognostic factors. 3,000 pts with 801 events are needed to show an increase of 5-year DFS from 75% to 79% for pts receiving EC→TX and 728 events to show an increase of 5-year DFS from 75% to 79.5% for pts receiving I, assuming a drop-out rate of 5%. A clinically relevant difference between the arms is to be detected at α = 0.05 (two-sided) with 80% power. Results: 3024 patients were recruited between June 2004 and August 2008. The trial was amended several times implementing an oral antibiotic prophylaxis, reducing the dose of C; reducing the dose of dexamethasone in the group receiving weekly T, and using an Hb adapted dosing of ESF. Conclusions: The therapy in the two regimen seems feasible if precautions are taken. Final safety data will be presented at the Meeting. [Table: see text]
Personalizing treatment in early-stage breast cancer: The role of standard clinical factors and genomic information in adjuvant chemotherapy decision making
Authors: Gold J. M. , Najita J. S. , Lester S. , Richardson A. L. , Morganstern D. E. , Chen W. Y. , Partridge A. H. , Krop I. E. , Winer E. P. , Burstein H. J. 
Published: August 2020

572 Background: The Oncotype DX recurrence score (RS) independently predicts the likelihood of benefit from adjuvant chemotherapy. However, the clinical factors that influence chemotherapy recommendations in addition to RS are not well characterized. We sought to determine how clinicians integrate the RS and standard clinicopathologic data when choosing adjuvant chemotherapy. Methods: We identified women with ER+, HER2-, LN- breast cancer seen at DFCI in whom RS testing was performed between November 2004 and October 2008. Clinical and pathological characteristics, RS and chemotherapy treatment were identified from electronic medical records. A multivariable model was used to examine which factors drove the decision to administer chemotherapy. Results: RS was performed on 269 women with the following case distribution: RS low (<18) 50%, RS intermediate (18–30) 41%, RS high (>30) 9%. Chemotherapy was given to 7% of women with low RS, compared to 42% and 86% of women with intermediate and high RS, respectively. Tumor grade, T stage, progesterone receptor expression and RS were associated with receipt of chemotherapy in univariate analyses but age, LVI and menopausal status were not. In a multivariable logistic regression model, tumor grade, size, and RS were independent predictors of chemotherapy administration. Conclusions: Oncotype DX RS plays a critical role in medical decision making for women with early stage breast cancer at this single academic institution. However, other tumor and clinical features independently contribute to chemotherapy decisions, suggesting that tailored treatment does, and should, integrate both traditional and molecular pathological factors. [Table: see text] No significant financial relationships to disclose.
Phase II trial of neoadjuvant sequential FEC100 followed by docetaxel and capecitabine for HER2-negative locally advanced breast cancer (LABC): A multicenter study from British Columbia
Authors: Chia S. K. , Lohrisch C. , Gelmon K. , Kennecke H. , Pansegrau G. , Taylor M. , Attwell A. , Jepson D. , Hayes M. , Shenkier T. 
Published: August 2020

598 Background: Anthracyclines and taxanes are now standard of care for LABC. Phase III trials have demonstrated pathological complete responses of the breast (pCR) of 20–34% in studies of primary operable and LABC. Recent trials in the HER-2 negative population reported pCR rates of 20–29%.We have completed a multi-centre phase II trial of a neoadjuvant sequential anthracycline and taxane combination regimen in a HER-2 negative LABC population. Methods: Women with HER-2 negative stage IIB-IIIC breast cancer were enrolled. Treatment consisted of 4 cycles of FEC100 (5-FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) followed by 4 cycles of XT (docetaxel 75 mg/m2 and capecitabine 1,000 mg/m2 PO BID x 14 days q3 weekly). Hormone receptor positive cases were prescribed standard endocrine therapy. A correlative translational component with baseline and interval biopsies and serum collection was also performed. Results: A total of 51 patients (27% stage IIB; 43% IIIA; 20% IIIB; and 10% IIIC) were accrued across 4 BCCA centres from November 2004-December 2007. Median age was 54 years (33–67 years). 59% of tumours were ER positive. There were no primary progressors on FEC100, though 2 patients had significant toxicities requiring early discontinuation. 3 patients (6%) developed clinical progression on XT. The majority of patients (79%) on XT required a dose reduction or delay. There were 5 episodes (10%) of febrile neutropenia. 15 patients (29%) underwent adjuvant radiotherapy prior to surgery. The pCR rate (breast and axilla) for the entire study population was 22% (11/51). In the ER+ and triple negative subtypes the pCR (breast and axilla) was 13% and 42%, respectively. Conclusions: This multi-centre phase II trial demonstrates activity for neoadjuvant anthracyclines followed by combination docetaxel/capecitabine in a HER-2 negative LABC population. Though the pCR rate was greater in the triple negative cohort, significant improvements are still required across the biological subtypes in HER-2 negative LABC. [Table: see text]
Biomarker potential of EGFR gene copy number by FISH in the phase III EXTREME study: Platinum-based CT plus cetuximab in first-line R/M SCCHN
Authors: Licitra L. , Rolland F. , Bokemeyer C. , Remenar E. , Kienzer H. , Stoerkel S. , Scheid S. , Stroh C. , Mesia R. 
Published: August 2020

6005 Background: Platinum-based CT + cetuximab is the first systemic therapy in ∼30 years to show a survival benefit vs platinum-based CT in first-line R/M SCCHN (Vermorken JB, et al. N Engl J Med 2008;359:1116–1127). A retrospective analysis has evaluated the influence of EGFR gene copy number, determined by FISH, on clinical outcome in the EXTREME study. Methods: Pts were randomized to 3-weekly cycles of platinum-based CT (cisplatin 100 mg/m2 or carboplatin AUC 5, day 1; 5-fluorouracil 1000 mg/m2/day continuous infusion, days 1–4) with or without cetuximab (initial dose 400 mg/m2, then 250 mg/m2 weekly). The proportion of FISH+ cells per pt (FISH score) was determined using 5 different enrichment models. Tumors were also classified as FISH+ or FISH- using the Colorado scoring system. Results: In the overall population (n=442), addition of cetuximab significantly improved median OS (10.1 vs 7.4 months; p=0.04). No association between FISH score and OS, PFS, or best overall response was determined for any enrichment model. Pts with Colorado FISH+ tumors were evenly distributed between the CT + cetuximab (50/158) and CT-alone (51/154) arms of the FISH- evaluable population (71% of ITT population). Colorado FISH status had no influence on OS in either treatment arm, on PFS in the CT-alone arm, or on RR in the CT + cetuximab arm (see table ). In the CT + cetuximab arm, pts with FISH+ tumors had a lower risk of progression than pts with FISH- tumors. Higher RRs among pts with FISH- tumors in the CT-alone arm may have been due to twice as many nonevaluable response observations in the FISH+ vs the FISH- population (percentage of pts with SD or PD was comparable). Conclusions: EGFR gene copy number, as determined by FISH, is not a predictive biomarker for cetuximab efficacy in R/M SCCHN. [Table: see text] [Table: see text]