bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of gimatecan as salvage treatment in patients with advanced or metastatic soft tissue sarcoma (STS) relapsing after anthracycline / ifosfamide - based chemotherapy regimens
Authors: Biron P. , Reichardt P. , Grosso F. , Le Cesne A. , Poveda A. , McCanna S. , Zanna C. , Brienza S. , Ray-Coquard I. , Blay J. Y. 
Published: March 2020

10063 Background: Gimatecan, a new oral camptothecin derivative, showed early clinical activity in patients with STS during the phase I clinical development. Methods: Patients with different histological types of STS, including rhabdomyosarcoma and Ewing's sarcoma of soft parts, and advanced or metastatic disease pretreated with anthracycline and ifosfamide were included. The principal inclusion criteria were: disease not curable with surgery and/or radiation, presence of a measurable progressive lesion(s), pretreatment with 1–3 lines of chemotherapy including adjuvant regimens, ECOG PS 0 to 1, age = 18 years. Gimatecan 0.8 mg/m2 was administered orally daily for five consecutive days every 4 weeks. Radiological response was assessed every two cycles by RECIST. A multicenter two stage Simon's optimal design was used to evaluate the single agent activity of gimatecan, also by means of a hierarchical Bayesian model to evaluate treatment effects within the histological subtypes, using the rate of progression free survival at 4 months (PFS- 4) (Van Glabbeke, Eur J Cancer 38: 543–549, 2002). Other objectives were safety, TTP, pharmacokinetics and biomarker evaluations. Results: From August 2005 to December 2006 40 patients, 24 (60%) males and 16 (40%) females, median age 48 years (range 21 - 77), were included in 5 European sites. As of December 2006, 14 patients (35%) achieved stable disease after a median of 4 (range 3–9) cycles, and the PFS-4 is 15% (hystotypes: leiomyosarcoma, liposarcoma, Ewing, synovial and unclassified); all PFS-4 patients had liver or pleuropulmonary metastases. A prolonged arrest of progression was observed in one Ewing (up to 9 months), in one leiomyosarcoma and one liposarcoma (up to 8 and 7 months respectively, both patients still on treatment). Main G3/4 toxicity was hematological, namely anemia (7.5%), thrombocytopenia (5%) and neutropenia (2.5%). Conclusions: These data suggest that oral gimatecan has produced durable disease stabilization and is well tolerated with less than 10% grade 3/4 haematological toxicities. [Table: see text]
Natural course and clinical features of myxoid and round cell liposarcoma (MRCL) - a retrospective single center analysis
Authors: Mispelaere B. , Sciot R. , Debiec-Rychter M. , Wozniak A. , Wolter P. , Dumez H. , De Wever I. , Samson I. , Amant F. , Schöffski P. 
Published: March 2020

10066 Background and methods: MRCL, the 2nd most common type liposarcoma, represents ∼10 % of adult soft tissue sarcomas. In most pts the karyotypic hallmark is t(12;16)(q13;p11), leading to fusion of CHOP and FUS genes and generation of a hybrid protein. MRCL has unique sensitivity to antineoplastic agent ET-743 (Yondelis, Trabectidin), which induces specific morphological change and long-lasting response. We made a retrospective analysis of MRCL cases in our center. Results: 33 pts had histological diagnosis of MRCL with a mean (mn) follow-up of 45 mo (range, 2–214). By karyotyping or FISH analysis CHOP-FUS fusion was present in 12 and CHOP-EWS in 2 pts. The mn age at diagnosis was 45 yrs (range, 18–71), male:female ratio 1:0.8. Frequent primary sites: lower limb (25), abdomen (5), retroperitoneum (2), neck (2). Stage grouping at diagnosis: IA (2), IB (6), IIA (5), III (14), IV (2), not known (NK) (4). 2 had distant spread, 9 metachronous metastasis with a mn interval of 24 mo (range, 5–84). Main sites involved: abdomen (5), lung (3), bone (3). Surgery was performed with curative intent in 26/28 pts (5 NK), R0 resection in 23. 17/28 pts are alive without disease (16 previously R0-resected). 6/28 are alive with disease, 5 died due to MRCL. Relapse after R0 resection occurred after a mn of 24 mo (range, 5–84). Radiotherapy was used in 15/28 (5NK) with neoadjuvant (1), adjuvant (13) or palliative (3) intent (total doses 50–66 Gy). Chemotherapy (CT) was given in palliative (11) or neoadjuvant (1) fashion, after a mn of 1.3 surgical interventions (range, 0–3). 1st-line CT: doxorubicin- based combinations (7), single-agent doxorubicin (3), ET-743 (1). Best response: PR (5), NC (4), PD (1), NE (1). Mn duration of response was 6.3 mo (range, 1–15). 2nd-line CT: ET-743 (3), other agents (4). Best response: CR (1), PR (1), NC (3), PD (1), NE (1), with mn response duration of 7 mo (range, 1–13). 2 had further CT (PR 1, SD 1). Conclusions: MRCL is a chemosensitive sarcoma with variable clinical course. Local treatment can be curative, but systemic spread is frequent. Pts may respond to conventional CT or new agents such as ET-743. To evaluate the relative value of systemic treatment we need randomized trials in this unique clinical setting. No significant financial relationships to disclose.
Prolongation of TTP by maintenance therapy with PLD in a multicenter phase III randomized trial following standard chemotherapy for MBC: GEICAM 2001–01 study
Authors: Alba E. , Ruiz-Borrego M. , Martín M. , Margelí M. , Rodríguez-Lescure Á. , Sánchez-Rovira P. , Ruiz A. , Ribelles N. , Calvo E. , Casado A. 
Published: March 2020

1007 Background: We had previously shown that sequential A→T is a reference treatment as first-line CT for MBC patients (pt) (JCO 2004, (22), 2587–2593). However, responses are short-lived and time to progression (TTP) is also short. Maintenance chemotherapy (MCT) with LPD could improve TTP without relevant additional toxicity. Methods: All pt received an induction CT with 6 cycles (cy) of A→T. Pt with a complete or partial response (CR, PR), or stable disease (SD) were randomly assigned to either LPD (40 mg/m2 q4wk × 6 cy) or observation (O) from May 2002 to Dec 2006. Eligible pt had adequate bone marrow, renal, hepatic and cardiac functions (by left ventricular ejection fraction, LVEF). The study hypothesis assumed a median TTP since start of induction CT in O arm of 10.5 months (m), and a prolongation of TTP of 66% with MCT. Therefore, 154 pt (77 per arm) were necessary (one-sided a and 1-β errors of 0.01 and 0.8). Results: Pt accrual was completed in December 06. 122 and 136 pt (60/66 in LPD vs. 62/70 in O) are currently evaluable for efficacy and safety. Median age was 57 yr (30–74). Status disease in pt assigned to LPD vs. O: 2 (3%) vs. 6 (9%) of pt had CR, 31 (47%) vs. 43 (61%) had PR; 33 (50%) vs. 21 (30%) had SD. 291 cy of LPD were administered (median 6, range 0–6). Neither relevant LVEF decrease nor clinical congestive failure were seen. Nausea/vomiting and alopecia incidence was negligible. G3 hand-foot syndrome was present in 3 pt/3 cy (5/1%). Median TTP in LPD arm was 16.04 m (14.06–18.02), vs. 9.96 m (8.87–11.05) in O arm, p=0.0001. Conclusion: Maintenance therapy with LPD significantly prolongs TTP in MBC pt after a first-line CT without significant clinical toxicity. No significant financial relationships to disclose.
Can ERCC1 and topoisomerase II-alpha predict histological response and outcome after induction chemotherapy in locally advanced soft tissue sarcomas (LASTS)?
Authors: Ruiz-Soto R. , Auger N. , Castaing M. , Drusch F. , Bonvalot S. , Terrier P. , Le Pechoux C. , Domont J. , Bénard J. , Le Cesne A. 
Published: March 2020

10074 Background: The impact of histological response (± 95% of necrosis) on patients (pts) outcome with LASTS treated by induction chemotherapy (CT) is still debated. Methods: From 1995 to 2005, 79 LASTS pts received induction CT consisting in two cycles of API-AI regimen and results were already reported (Gomez-Abuin, ASCO 2004). ERCC1, HER2 and Topoisomerase IIa (TopoII) was assessed by IHC on initial biopsies after paraffin embedding and correlated to histological response and pts outcome. Results: The median age of the 43 males and 36 females was 43 years (yr) (range 18–68) and the median tumor size at diagnosis was 109 mm (range 10–250 mm). CR was achieved in 4 pts, PR in 25 pts, SD in 45 pts and PD in 5 pts. R0 surgery was possible in 82% of pts; histological necrosis (HN) after chemotherapy was >95% in 25 pts, between 50–95% in 28 pts and <50% in 25 pts (median HN was 70%). All pts but one received postoperative radiotherapy. Relapse occurred in 37 pts; local in 3, distant in 33 and both in 1. After a median follow-up of 48 months (9–118 months) 51 pts are alive. The 5 yr DFS and OS were 45% and 60% respectively. Multivariate analysis correlated median HN to a better EFS and a non grade 3 to a better OS. Regarding protein expression (54 pts analyzed), a higher protein expression of TopoII was correlated to a better EFS (p=0.032) by univariate analysis and to OS by multivariate analysis (p=0.025). ERCC1 protein expression was not related to EFS and/or OS. There is no correlation between over expression of both proteins and any percentage of HN. Conclusions: A high rate of HN (> 70%) after induction chemotherapy treatment is predictive for a better EFS. TopoII expression seems to be a relevant early predictive marker for outcome of pts with LASTS treated with doxorubicine-containing induction CT. No significant financial relationships to disclose.
Combination of trabectedin (T) and doxorubicin (D) for the treatment of patients with soft tissue sarcoma (STS): Safety and efficacy analysis
Authors: Blay J. , von Mehren M. , Samuels B. L. , Fanucchi M. P. , Ray-Coquard I. L. , Buckley B. , Gilles L. , Lebedinsky C. , Elsayed Y. A. , Le Cesne A. 
Published: March 2020

10078 Background: T is a novel marine-derived DNA minor-groove binder that interferes with gene activation, nucleotide excision repair, and induces DNA strand breaks and cell cycle arrest in S and G2. T is active in STS and exhibits preclinical synergy with D. The objective of this study was to determine the combination regimen that is tolerable and associated with manageable neutropenia. Other objectives included safety, clinical activity and pharmacokinetics (PK) Methods: This was a dose escalation phase I study. Eligible patients (pts) had metastatic or recurrent STS, PS 0–1, and adequate organ function. Pts with more than 1 prior chemotherapy, prior anthracyclines or radiation to more than 20% of bone marrow were excluded. On day 1 of each 3-week cycle, pts received D starting at 60 mg/m2 followed by T starting at 0.9 mg/m2. Incremental doses were explored. D was discontinued after 6–8 cycles. Treatment was administered as an outpatient. PK samples were collected. A modified dose escalation and dose modifications were implemented Results: Forty one pts were treated in three sequential cohorts. In cohort 1 (D60 mg/m2 + T0.9 mg/m2), 4/11 pts without G-CSF experienced unmanageable neutropenia and subsequently prophylactic G-CSF was instituted. No unmanageable neutropenia was seen in the subsequent18 evaluable pts in this cohort. 1/13 and 2/6 DLTs were seen in cohort 2(D60 mg/m2 + T1.1 mg/m2) and cohort 3(D60 mg/m2 + T1.3 mg/m2) respectively. The most frequent grade 3/4 AEs were: neutropenia(71%), ALT elevation(46%), thrombocytopenia34%), AST(24%), anemia (22%), Febrile neutropenia (17%). One pt discontinued due to grade 3 asthenia. The MTD and recommended dose is D60 mg/m2 + T1.1 mg/m2. Anti-tumor activity included 17% ORR (1 CR and 6 PR), 80% stable disease (45% SD>6 months). Median PFS is 8.9 months (95% CI 5.6–11.8). 3-month and 6-month PFS are 85.4% and 58.2% respectively. Mature overall survival and PK data will be presented Conclusions: The combination of T and D with G-CSF support is safe, tolerable and active in pts with metastatic or recurrent STS [Table: see text]
Lapatinib (L) with paclitaxel compared to paclitaxel as first-line treatment for patients with metastatic breast cancer: A phase III randomized, double-blind study of 580 patients
Authors: Leo A. Di , Gomez H. , Aziz Z. , Zvirbule Z. , Arbushites M. , Oliva C. R. , Koehler M. , Williams L. S. , Dering J. , Finn R. S. 
Published: March 2020

1011 Background: L is an oral tyrosine kinase inhibitor of EGFR/HER2, active as monotherapy and in combination for HER2-overexpressing advanced/metastatic breast cancer (BC). A Phase I study of L with paclitaxel (P) indicated no unexpected adverse events (AEs). PK profile indicated no relationship between peak plasma concentration of P+L and neuropathy, neutropenia, diarrhea, rash or myalgia. We report here blinded efficacy and safety data for patients (pts) with incurable Stage IIIb/IIIc/IV BC at first diagnosis or relapse, untested or negative (0/1+ IHC or FISH neg) for HER2. Unblinded data will be presented at ASCO 2007. Methods: Between Jan 2004 and Jul 2005, 580 pts from 24 countries were stratified by metastatic site and randomized 1:1 to L 1500 mg QD + 175 mg/m2 P q3w or placebo QD + 175 mg/m2 P q3w. Primary endpoint was TTP; secondary endpoints were AEs, ORR, PFS, CBR, RFS, and OS. Tumor tissue was obtained from the most recent biopsy of 451 (78%) pts and was centrally analyzed in blinded fashion for biomarker patterns. Serum samples were collected for central EGFR and HER2 ECD analysis. Results and Conclusions: 579 pts were analyzed; 87% presented with Stage IV BC. 55% received prior adjuvant chemotherapy or anti-hormonal therapy. No pts received previous trastuzumab. At the time of analysis, 561 (97%) pts progressed or otherwise withdrew. Most common AEs were alopecia (58%), neurological (55%, gr=3:8%), diarrhea (42%, gr=3:9%), nausea (32%), and rash (32%, gr=3:2%). Neutropenia and thrombocytopenia AEs related to study treatment were 18% and <1%, respectively. LVEF decrease of 20% relative to baseline and below LLN was reported 15 times. 12% of AEs led to treatment withdrawal. Blinded data analysis revealed a median TTP of 25 wks and ORR of 30%. CNS relapse was reported in 11 pts (2%). Enrollment predominantly came from countries with limited HER2 testing capacity thus a subgroup of pts is expected to be HER2+ve. Blinded analyses of HER2, ER and PR are ongoing at this time and final biomarker evaluations will be presented with unblinded efficacy data. [Table: see text]
Safety and efficacy of capecitabine (C) plus bevacizumab (B) as first-line in metastatic breast cancer
Authors: Sledge G. , Miller K. , Moisa C. , Gradishar W. 
Published: March 2020

1013 Background: C alone has good activity and tolerability in metastatic breast cancer (MBC) and when combined with docetaxel improves response and survival. C combined with B in heavily pretreated MBC improved the response rate but not PFS. In untreated MBC, the addition of B to chemotherapy significantly improves progression-free survival (PFS) which suggests that B, is most effective in early disease. Methods: Primary objective of this single-arm, 2-phase study, is to evaluate PFS in MBC patients receiving first-line treatment with C 1,000 mg/m2 twice daily on days 1–15 (28 doses) and B 15 mg/kg on day 1. Treatment was repeated every 21 days until progression. Eligibility criteria included HER2-negative MBC previously untreated for metastatic disease; ECOG performance status =1; no prior anti-angiogenic or oral fluoropyrimidine therapy. A sample size of 109 patients (including dropouts) was required to give 90% power to test an improvement from 4 months median PFS to 5.6 months with the two-sided test (a 5%) Results: At data cut-off, 103 patients had received study medication. Present results are based on 103 patients (ITT population), except tumor response which is based on 91 patients who had response evaluation. The average # of cycles received in first phase is 6.8. 84 pts.are alive at this time. 38.5% (35/91) pts. have had a response: complete response 5.5%; partial response 33.0%. Stable disease is 42.9% with 81.4% clinical benefit. Planned dose received is 77.7 % for C and 99.0 % for B. The majority of adverse events (AEs) were mild or moderate. The most common grade 3 AEs were hand-foot syndrome (13%) and pain (10%); grade 4 pulmonary embolism occurred in 2% in the first phase of the study. Conclusions: Updated results with longer follow-up including toxicity, TTP and PFS will be presented at the meeting. It appears that in first-line C+B is active for MBC and is well tolerated, with few grade 3/4 toxicities. [Table: see text]
Detecting circulating tumor cells in metastatic breast cancer patients using fiber-optic array scanning technology
Authors: Marrinucci D. , Bethel K. , Lazarus N. , Leach M. , Kroener J. , Bruce R. , Kuhn P. , Nieva J. 
Published: March 2020

1022 Background: Circulating tumor cell (CTC) detection and enumeration has been shown to be a valuable tool for determining prognosis in metastatic breast cancer patients. CTCs are rare, existing in the circulation at estimated concentrations of 1 in 1 - 10 million normal blood cells. To date, the most widely used technique to detect CTCs has used immunomagnetic enrichment based protocols. In this validation study, we sought to determine if an enrichment free approach using an immunofluorescent cell attachment protocol along with fiber-optic array scanning technology (FAST) could achieve similar results. Methods: We have developed and validated a scanning instrument using FAST that can be used in conjunction with an immunofluorescence staining protocol to efficiently detect CTCs. The protocol uses a pan anti-cytokeratin antibody cocktail directed against 9 cytokeratins along with a DAPI nuclear counterstain. FAST defines cell positions, so relocation and retrospective analysis of CTCs is possible. Using this system, we assayed 50 blood specimens obtained from metastatic breast cancer patients. Pathologic review of CTCs was performed identifying CTCs as cytokeratin positive and DAPI positive. Survival analyses were determined using Kaplan-Meier analyses. Results: 31 women with metastatic breast cancer were enrolled in the study and provided 50 peripheral blood specimens. The median CTC count for patients with progressive disease was 8.5, while the median CTC count for patients with stable or responding disease was 1. At a median follow-up of 1 year, 11 patients had died. Patients with =5 CTCs had a median survival of 212 days, while the median survival for patients with 0–4 CTCs had not been reached after 1 year (p=0.0012). Patients with progressive disease had significantly higher CTC counts (p<0.0001) than those who were stable or responding to therapy. Conclusions: This study confirms the previously reported efficacy of CTC enumeration in determining the prognosis of metastatic breast cancer patients and establishes the potential utility of the FAST cytometer as a method for CTC enumeration. No significant financial relationships to disclose.
A randomized trial of capecitabine (C) given intermittently (IC) rather than continuously (CC) compared to classical CMF as first-line chemotherapy for advanced breast cancer (ABC)
Authors: Stockler M. , Sourjina T. , Grimison P. , Gebski V. , Byrne M. , Harvey V. , Francis P. , Nowak A. K. , Van Hazel G. , Forbes J. 
Published: March 2020

1031 Background: Intensive treatment is not indicated for many women having first line chemotherapy for ABC. We sought to determine for such women whether oral C was preferable to classical CMF, and whether C given continuously (CC) was preferable to the same total dose given intermittently for 14 of every 21 days (IC). Methods: 325 women were randomized between June 01 and July 05 to either IC (2,000mg/m2/d for 14 of every 21d), or CC (1,300mg/m2/d for 21 of every 21d), or CMF (cyclophosphamide 100mg/m2/d p.o. d1–14; methotrexate 40mg/m2 and 5-FU 600mg/m2, IV d1&8, every 28d). Treatment was continued until disease progression (PD), unacceptable toxicity, or intolerance. Clinical and quality of life (QOL) assessments were 3–4 wkly, and imaging was 3 monthly, both until PD. The primary endpoint was quality adjusted progression-free survival (QAPFS). Overall survival (OS), PFS, response rates (RR=CR+PR), QOL, acceptability of chemotherapy and adverse events (AE) were secondary endpoints. The analysis plan was to first compare IC v CC, and if p>0.05, then to combine the two arms (C = IC + CC) for comparisons v CMF. Primary analyses were with the logrank test. Cox’s models were used to calculate hazard ratios (HR), 95% confidence intervals (CI), and to adjust for other factors. All p-values and CI are 2-sided. Results: OS was longer with C than CMF (HR .72, CI .55 to .94, p=.02, medians 22 v 18 mo). PFS was similar for C and CMF overall (HR .86, CI .67 to 1.1, p=.2, median 7 mo), and over the first 6 mo (HR 1.15, CI .81 to 1.6), but longer on C than CMF beyond 6 mo (HR .62, CI .44 to .87). Response rates were similar on C and CMF (21% v 18%, p=.8). Febrile neutropenia, infection, and sore mouth were more common on CMF; hand-foot syndrome was more common on C. Chemotherapy was continued beyond 6 mo in 40% on C but only 21% on CMF. PFS, OS, RR and AE were similar for IC and CC (p>0.4). Cox’s models adjusting for baseline factors corroborated all results and conclusions. Analyses of QAPFS, QOL, and acceptability of chemotherapy will be available in June 07. Conclusion: C improved overall survival with less toxicity and greater tolerability than classical CMF. C is a good first line option when more intensive treatment is not indicated. [Table: see text]
Randomized comparison of weekly or every-3-week (q3w) nab-paclitaxel compared to q3w docetaxel as first-line therapy in patients (pts) with metastatic breast cancer (MBC)
Authors: Gradishar W. , Krasnojon D. , Cheporov S. , Makhson A. , Manikhas G. , Clawson A. , Hawkins M. J. 
Published: March 2020

1032 Background: 130-nM albumin-bound (nab™) paclitaxel combines paclitaxel with albumin without solvents or altering either component. A cross analysis of 2 clinical trials comparing solvent-based (SB) paclitaxel 175 mg/m2 q3w to nab- paclitaxel (Gradishar et al, JCO, 2005) and SB docetaxel (Jones et al, JCO, 2005) suggested comparable antitumor activity between nab-paclitaxel and SB docetaxel and better tolerability with nab-paclitaxel in pts with MBC. The aim of this study was to compare the toxicity and antitumor activity of 3 regimens of nab-paclitaxel (q3w and 2 weekly) with each other and that of SB docetaxel in MBC. Methods: In this open-label study, first-line pts with MBC were randomly assigned to nab-paclitaxel 300 mg/m2 q3w (A); nab-paclitaxel 100 mg/m2 (B) or 150 mg/m2 (C) days 1, 8, and 15, q28 days (q 3/4 w); or SB docetaxel 100 mg/m2 q3w (D). The primary endpoints were overall response rate (complete response + partial response, evaluated q8w) and toxicity. Progression-free survival (PFS) was also determined. Results: 302 pts (median age, 54 years; 99% Caucasian; 75% postmenopausal; ECOG PS =2 [94% =1]) either had at least 2 response assessments (94%) or had discontinued due to PD (6%). The efficacy results are shown in the Table . Neutropenia (N) was greater with D than with A, B, or C (p < 0.001). Grade 4 N was: A) 4%, B) 3%, C) 7%, and D) 74%. Febrile neutropenia (FN) was: A) 1%, B) 1%, C) 1%, and D) 7%. Gr 3 peripheral neuropathy was: A) 14%, B) 7%, C) 12%, and D) 5%. Conclusions: The response rates of q3w nab-paclitaxel and solvent-based docetaxel were comparable. Q 3/4 W nab-paclitaxel resulted in higher response rates than solvent-based docetaxel. Grade 4 N and FN were less frequent with nab-paclitaxel as compared with solvent-based docetaxel. To date, all 3 nab-paclitaxel regimens have a longer PFS than SB docetaxel although the data are not yet mature (33% of events). Final data for a radiological review of response data, PFS, and toxicity will be presented. [Table: see text] No significant financial relationships to disclose.