bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the impact of relative total dose intensity (RTDI) on patient's short- and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer: A pooled analysis
Authors: Loibl S. , Nekljudova V. , Skacel T. , Schwenkglenks M. , Lück H. , Brodowicz T. , Zielinski C. , von Minckwitz G. 
Published: August 2020

1065 Background: The consequences of reducing chemotherapy dose intensity might be extensive, potentially affecting short- and long-term outcomes as well as patient quality of life, the dose and schedule are of central concern in the delivery of chemotherapy. Methods: This statistical analysis was based on individual subject data of 934 patients (pts) obtained from the following prospective, open-label, randomised phase III trials in metastatic breast cancer that recruited between 1996 and 2005 investigating an anthracycline/taxane based first-line chemotherapy: CECOG trial, AGO-Mamma-1 and AGO-Mamma-3 trial. The primary objective of the analysis was to evaluate the influence of RTDI on progression free survival (PFS) in different predefined binary RTDI cuts from 75% to 95% with an interval at every 5%. Relative total dose intensity (RTDI) is the ratio of actual total dose intensity and planned total dose intensity, expressed as a percentage. RTDI quantifies dose reductions and delays, as well as premature discontinuations in treatment. Results: Overall cuts pts with higher RTDI had a shorter PFS compared to those with lower RTDI. A time dependent term for low RTDI was included in the analysis and showed the opposite effect after approximately 60 weeks. The overall median PFS was 39 weeks. Analysis of the Kaplan-Meier curve identified many early events in patients with high RTDI. We hypothesized that patients with a primary progression (PP) who have by definition a high RTDI were responsible for this effect. The PFS excluding 114 patients with PP showed no difference for patients with high compared to those with low RTDI. The median overall survival (OS) for the whole study population was 98 weeks. Excluding patients with PP, the median OS was 118 weeks (95% CI [103–136]) for those with RTDI ≥ 85% versus 96 weeks (95% CI [83–119]) if RTDI was < 85% (log-rank p = 0.0086). The results were comparable across other cut levels. Conclusions: Maintaining RTDI in patients not experiencing PP might have significant impact on overall survival. No significant financial relationships to disclose.
Phase I trial of escalating doses of weekly everolimus (RAD001) in combination with docetaxel for the treatment of metastatic breast cancer (MBC)
Authors: Moulder S. L. , Rivera E. , Ensor J. , Gonzalez-Angulo A. , Christofanilli M. , Booser D. , Giordano S. , Brewster A. , Hortobagyi G. , Tran H. 
Published: August 2020

1066 Background: Inhibition of mTOR with everolimus (E) may improve efficacy in combination with docetaxel (D), but both drugs are metabolized by CYP3A4, thus a pharmacokinetic (PK) interaction may also exist. Methods: 15 patients (pts) with MBC were treated with docetaxel and everolimus using the continuous reassessment method (CRM) to determine maximum tolerated dose (MTD). Docetaxel doses were 40–75 mg/m2 IV on day 1 of a 21 day cycle. Everolimus doses were 20–50 mg PO on days 1 and 8 of a 21 day cycle (except cycle 2, where only day 8 was given to allow single agent PK analyses of both drugs). Response was measured every 2 cycles using RECIST. Results: Median age= 58 years and 77% of pts had >2 prior chemotherapies for MBC. Initially 2 of 2 pts treated (D= 75 mg/m2, E= 30 mg) developed DLT (neutropenic fever/infection), prompting a mandatory PK evaluation for all pts enrolled in subsequent cohorts. A second cohort of 3 patients (D=60 mg/m2, E=20mg) had no DLT, but no pts received day 8 of E due to grade 3–4 neutropenia. PK analyses demonstrated a 42% lowered (-42%) D clearance at the 60 mg/m2 in the presence of E (n=1). Subsequent cohorts were accrued at D=40 mg/m2 with escalating doses of E (Table). For the entire group, an 18% decrease (-18%) in D clearance was observed when D was administered concomitantly with E. High interpatient variability of D clearance was observed (range +16% to -135%). No pts had CR/PR, but 6 had SD>4 cycles and 2 had SD=8 cycles. Conclusions: Weekly everolimus appears to cause widely variable and unpredictable changes in docetaxel clearance making this combination unfeasible. [Table: see text] No significant financial relationships to disclose.
Preliminary results of a phase II study of liposomal cisplatin-vinorelbine combination as first-line treatment in HER2/neu negative metastatic breast cancer (MBC)
Authors: Farhat F. S. , Ibrahim K. , Kattan J. , Bitar N. , Jalloul R. , Nsouly G. , Ghosn M. , Haddad N. , Bou Karroum M. , Tamraz S. , Shamseddine A. 
Published: August 2020

1068 Background: The frequent use of anthracyclines and taxanes in breast cancer's adjuvant setting has lead to drug resistance and cardiac toxicity. This has raised the need for new agents in the metastatic setting. Cisplatin-vinorelbine combination recently showed interesting results with an overall response rate of 64%. Nevertheless, the use of cisplatin was limited by the frequently induced nausea, vomiting, and nephrotoxicity. Liposomal cisplatin (Lipoplatin) is a nontoxic alternative agent to cisplatin. The aim of this study is to evaluate the efficacy and safety of liposomal cisplatin-vinorelbine combination in first line MBC patients (pts). Methods: From August 2007 to October 2008, 30 of 35 programmed pts with MBC and no prior treatment for their metastatic disease, PS 0–2, HER2/neu negative, and at least one measurable lesion, were enrolled. Of these 30 recruited pts, 26 with available data were analyzed. Treatment included I.V. vinorelbine 30 mg/m2 on days 1 and 8, and liposomal cisplatin 120 mg/m2 on days 1, 8, and 15. Cycles were repeated every 3 weeks for a total of 6 cycles. Primary objectives: objective response rate, time to treatment failure (TTF), and time to progression (TTP). Secondary objectives: overall survival and treatment-related toxicity. Results: The median age was 49 years (29–74). 69% of pts had visceral metastases. 35% had one metastatic site, 46% had 2, 19% had 3 or more. A total of 120 cycles were administered with a median number of 6 per patient. At the time of the analysis 22 pts were evaluable for response. An objective tumor response was observed in 11 pts (50%) and complete response in 1 patient (4.5%). Ten (45.5%) pts had stable disease. The median TTF and TTP were 5 and 8 months respectively. All pts (26) were evaluable for toxicity. The majority of adverse events were mild to moderate. No WHO grade 3–4 nephrotoxicity or neuropathy was noted. Grade 3–4 nausea/vomiting was observed in 3 pts (11.5%). Three pts (11.5%) had grade 3 anemia and 18 pts (69.2%) had grade 3–4 neutropenia. Three pts (11.5%) developed febrile neutropenia with no secondary mortality. Conclusions: The new combination of liposomal cisplatin and vinorelbine shows promising activity and good tolerance as first line treatment for HER2/neu negative MBC. Pts’ enrollment is ongoing. Updated results will be presented at the meeting. [Table: see text]
What is the evidence for rechallenging with anthracyclines or taxanes in metastatic breast cancer? A review of the data
Authors: Krell J. , Harper-Wynne C. , Miles D. , Misra V. , Cleator S. , Krell D. , Palmieri C. 
Published: August 2020

1072 Background: Anthracyclines and taxanes are widely used in the adjuvant setting for high risk, early stage breast cancer. This raises the issue of what is the optimal therapy for those patients who relapse, and what the potential role, if any, there is for rechallenge with these agents. The current evidence base for rechallenging with anthracyclines/anthracediones and taxanes in metastatic breast cancer (MBC) is examined in this study. Methods: Medline/Pubmed database searches were performed upto October 2008 to identify studies in which patients (pts) were rechallenged with anthracyclines/anthracediones or taxanes in MBC. Results: The efficacy data, as well as the safety data relating to neurotoxicity and cardiotoxicity from these studies, are summarized in the Table. Twenty-seven studies were identified (20=anthracycline/anthracedione, 7= taxane) of which only two were prospective studies. Both were small (n= 74 & 51) and related to anthracycline rechallenging. Conclusions: Evidence exists to support rechallenging with anthracyclines and taxanes. However, there are few prospective data on reexposure to taxanes and no data comparing anthracyclines versus taxanes following adjuvant exposure to both agents, supporting the need for clinical trials in this area. Such trials should ideally incorporate a cross-over design at treatment failure, which would shed light on the optimal sequence in which these agents should be administered. [Table: see text] No significant financial relationships to disclose.
A phase I/II trial of ispinesib, a kinesin spindle protein (KSP) inhibitor, dosed q14d in patients with advanced breast cancer previously untreated with chemotherapy for metastatic disease or recurrence
Authors: Gomez H. L. , Philco M. , Castaneda C. , Pimentel P. , Escandon R. , Seroogy J. , Saikali K. , Wolff A. , Conlan M. 
Published: August 2020

1077 Background: KSP is a mitotic kinesin essential for cell cycle progression. Ispinesib, a selective KSP inhibitor, blocks mitotic spindle assembly with cell cycle arrest in mitosis and subsequent cell death. On a q21d schedule, the MTD was 18 mg/m2. In a phase II trial of ispinesib dosed at 18 mg/m2 q21d in patients (pts) with advanced breast cancer after anthracycline and taxane failure, the response rate was 4/45 (9%). This trial evaluates ispinesib given on d1 and d15 q28d, thus increasing dose density. Methods: In phase I of this phase I/II trial, DLT and MTD of ispinesib given d1 and d15 q28d will be determined. Eligibility criteria: advanced breast cancer; no prior chemotherapy (CT) except neoadjuvant or adjuvant and ≥ 1 yr elapsed since CT; no CNS metastases; ECOG 0–1. This is a standard 3+3 dose escalation trial design, starting at 10 mg/m2 and escalating based on tolerability in cycle (cy) 1. Pharmacokinetic data are collected in cy 1. Results: Phase I of the trial is ongoing. 16 pts were treated at 3 dose levels: 10 (n = 3), 12 (n = 6), and 14 mg/m2 (n = 7). 9 pts were stage IV; 11 were chemo-naïve; 5 had prior anthracycline and/or taxane; 4 were HER-2+ and 5 ER-, PR-, HER-2-. The most frequent toxicity was neutropenia. 88% of pts in cy 1 (grade 3/4 in 75%; no febrile neutropenia). Mild GI toxicity occurred in <37.5% of pts. There was no neuropathy or alopecia. At the 14 mg/m2 dose level, 2/7 pts had DLTs of transient grade 3 AST and ALT increases after cy 1 d15 dosing; both without increases upon retreatment; 1 in a pt with liver metastases; neither pt had significant increases in alkaline phosphatase or bilirubin. The 12 mg/m2 cohort was expanded to 6 pts without DLT. 3 pts had partial response (after 1 [n = 1] and 4 [n = 2] cy, respectively); 1 confirmed and ongoing after 8+ cy; 4 pts had stable disease ≥4 mo. Conclusions: Ispinesib appears to be well tolerated on a q14d dosing schedule at doses tested to date. A dose-density equal to that given in the prior phase II trial (0.86 mg/m2/d) was tolerated with the q14d schedule with preliminary evidence of efficacy. Further exploration of the 14 mg/m2 dose level is planned. [Table: see text]
Anastrozole and goserelin combination as first treatment for premenopausal receptor positive advanced or metastatic breast cancer: A phase II trial
Authors: Roche H. H. , Thierry D. , Chieze S. , Pierre K. , Veyret C. , Abadie S. , Campone M. , Florence D. 
Published: August 2020

1079 Background: Aromatase inhibitors (AIs) have shown high activity in postmenopausal women. However, as AIs do not suppress ovarian oestrogen synthesis, they are not effective in premenopausal women. The aim of this trial was to assess the efficacy of the combination of anastrozole and goserelin (LHRH agonist) in premenopausal women with advanced or metastatic hormonal receptor positive breast cancer. Methods: Premenopausal women with advanced estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer were enrolled in this open, multicentre, non-comparative phase II trial and received anastrozole 1mg/day p.o. and gosereline 3.6 mg subcutaneously monthly until progression. The primary endpoint was objective response rate (ORR) assessed according to RECIST criteria. Results: Thirty-three patients (33), with a mean age of 44 (+ 5.9) years, PS 0–2, were enrolled from December 2001 to May 2005. All patients were ER positive and 75.8% PR positive and 6 patients (18.2%) received adjuvant treatment with anti estrogens. There were 4 (12.1%) complete responses (CR), 14 (42.4%) partial responses (PR), and 11 (33.3%) stable diseases (SD), giving an ORR of 54.6% (IC 95% [36.4; 71.9]). Twenty-one (63.6%) patients showed a clinical benefit (CR+PR+SD≥24 weeks) for a median duration of 13.7 (IC 95% [8.74; 22.97]) months. Median time to progression was 13 (6;33) months. The most commun AEs were hot flush in 29 (87.9%), arthralgia in 13 (39.4%) and nausea in 12 (36.4%) patients. Conclusions: The combination of anastrozole and gosereline is well tolerated and appears to be an effective treatment of premenopausal women with advanced breast cancer in this exploratory phase II trial. No significant financial relationships to disclose.
Impressive survival data with semimetronomic oral chemotherapy with old agents in heavily treated metastatic breast cancer patients
Authors: Mutlu H. , Bozcuk H. , Ozdogan M. , Artac M. , Coskun H. S. , Kargi A. , Uysal M. , Savas B. 
Published: August 2020

1082 Background: To assess the efficacy of semi-metronomic regimen metronomic cyclophosphomide with oral etoposide in heavily treated patients with metastatic breast cancer. Methods: Consecutive metastatic breast cancer (MBC) patients predominantly refractory to antracyclines, taxanes, and antimetabolites receiving semi-metronomic regimen of metronomic cyclophosphomide with oral etoposide were evaluated for clinical efficacy and toxicity. This novel regimen comprised of continuous oral cyclophosphomide 50 mg/day, and oral etoposide given as 2 x 50 mg/day for 5 days. Results: A total of 42 MBC patients received this treatment in 2.5 years (May 2005-October 2008). The median age was 51.5 (29–81), ER and/or PR receptor status was positive in 67%, and c-erb-B2 overexpression existed in 50%. The biologically favorable group, hormone responsive and c-erb-B2 negative comprised of 36% of cases. The portions of patients with visceral metastases, cranial metastases, and 2 or more organ involvement were 82%, 24%, and 65%, respectively. Subjects had received this treatment in the fourth or more advanced setting in 50% of cases (after a median of 2.5 cycles). The median overall and progression free survival figures were 25 and 10.5 months, respectively. No toxic mortality occurred, and the treatment was well tolerated. Toxicity and response data are being updated currently. Conclusions: Semi-metronomic treatment with metronomic cyclophosphomide and oral etoposide is a novel and effective strategy in heavily pretreated MBC patients. Survival data and low cost may make this regimen a highly preferable option in this difficult patient group. No significant financial relationships to disclose.
Phase II study of sagopilone (ZK-Epo) in patients with recurrent metastatic breast cancer (MBC)
Authors: Morrow P. H. , Divers S. G. , Provencher L. , Luoh S. , Petrella T. M. , Giurescu M. , Fielding L. , Wang Y. , Hortobagyi G. N. , Vahdat L. T. 
Published: August 2020

1083 Background: Sagopilone is a novel, fully synthetic epothilone, which represents a new class of microtubule stabilizing agents. It has shown significant pre-clinical activity in taxane resistant breast cancer cell lines and in tumor models, as well as clinical activity in both taxane naïve and pretreated MBC. Methods: MBC patients who received ≤ 3 prior anthracycline and taxane containing chemotherapies were eligible. Sagopilone was given either at 16 mg/m2 (arm A) or at 22 mg/m2 (arm B, amended additional cohort) IV over 3 hours every 21 days for up to 6 cycles. The primary end point was tumor response by RECIST. The Simon 2-Stage design required 3 responders in the first 24 evaluable patients in stage 1 and 10 responders in 65 evaluable patients to declare success. Results: Between June 2006 and June 2008, 65 patients were enrolled and treated (39 in arm A, 26 in arm B). Majority of metastases were in lymph nodes (62%), liver (55%), bone (49%), lung (37%), and cutaneous sites (19%). Median number of cycles delivered was 2 (1–17). Neither arm met Stage 1 criteria for responders. Nevertheless, 2 patients in arm A and 1 in arm B had confirmed partial response, and lasted 4, 7, and 2 months, respectively. 26% patients in arm A, and 42% in arm B had stable disease. 42 patients discontinued study prior to cycle 6 due to progressive disease/death, 14 due to adverse events, and 1 due to other reasons. All 65 patients are evaluable for safety. Adverse events documented or reported in ≥ 20% patients are: sensory neuropathy 80% (23% grade 3), nausea 57% (no grade 3), fatigue 45% (12% grade 3), vomiting 29% (no grade 3), myalgia 28% (5% grade 3), diarrhea 25% (2% grade 3), insomnia 25% (no grade 3), pain in extremity 25% (2% grade 3), headache 23% (5% grade 3), arthralgia 22% (5% grade 3), constipation 22% (2% grade 3). Conclusions: Sagopilone had limited activity in these heavily pretreated MBC patients. It appeared tolerable at both dose levels. [Table: see text]
A novel metronomic schedule of oral vinorelbine for the treatment of metastatic breast cancer in elderly patients: A phase II trial
Authors: Addeo R. , Faiola V. , Cennamo G. , Guarrasi R. , Montella L. , Iodice P. , Sgambato A. , Capasso E. , Caraglia M. , Del Prete S. 
Published: August 2020

1085 Background: Oral vinorelbine (VNR) is particularly useful in elderly patients due to its favorable toxicity profile. Several studies demonstrated that this drug seems to represent an active treatment for metastatic breast cancer (MCB). We evaluated the clinical efficacy and tolerance of metronomic chemotherapy with oral VNR. Methods: Women were eligible if they had a histologically proven untreated MBC and were > 70 years old. A two-staged Simon accrual design was adopted for this phase II trial. Patients were required to have negative estrogen receptor status, at least one bidimensionally measurable target lesion, Karnofsky performance status >70; life expectancy > 3 months. Each patient received oral vinorelbine 80 mg/m2 fractionated in days 1, 3, and 5, three week on-one week off, every 4 weeks, for a maximum of six cycles unless disease progression or unacceptable toxicity. Results: Thirty-two patients with MBC were eligible, assessable for response, and toxicity. The median age was 75 years (range 70–84), sixteen patients (50%) had a Karnofsky performance status of 90–100. The main comorbidities recorded were: hypertension in 9 (28%) patients and diabetes mellitus in 6 (19%). The overall response rate (on an intent-to-treat basis) was 41% (13 of 32; 95% CI, 20%-54%). Two complete response and 11 partial responses were noted. In addition, other 10 patients (31%) had stable disease of > 4 months duration, and 9 patients (28 %) had disease progression. Median time to disease progression was 7.1 months and median overall survival was 12.7 months. The schedule was well tolerated, grade 3 toxicity was observed only in two patients. Conclusions: Metronomic oral VNR can be safely administered to elderly patients with MBC and is active in this population. Final data analysis will be presented. No significant financial relationships to disclose.
Fulvestrant in the treatment of advanced breast cancer: A systematic review and meta-analysis of randomized controlled trials
Authors: Mauri D. , Valachis A. , Polyzos N. P. , Mavroudis D. , Georgoulias V. , Casazza G. 
Published: August 2020

1087 Background: The purpose of the study was to compare efficacy and tolerability of fulvestrant with aromatase inhibitors and tamoxifen that actually represent the standard of care in hormonesensitive breast cancer. Methods: Systematic review and meta-analysis of available trials. Primary outcomes were overall survival, time to progression, clinical outcome, and objective response. Secondary outcome was the tolerability profile of the drugs. Results: Four trials were identified with 2,125 eligible patients. There was no statistically significant difference between fulvestrant and other hormonal agents in terms of overall survival (pooled HR: 1.047, 95% CI: 0.688 to 1.592), time to progression (pooled HR: 0.994, 95% CI: 0.691 to 1.431), clinical benefit (pooled OR: 1.044, 95% CI: 0.828 to 1.315), or objective response rate (pooled OR: 0.949, 95% CI: 0.736 to 1.224). A higher incidence of joint disorders (pooled OR: 0.621, 95% CI: 0.424 to 0.909; p = 0.014) was noted in patients receiving hormonal agents other than fulvestrant. Conclusions: Fulvestrant was similar to other hormonal agents with respect to efficacy measures, with good tolerability profile. No significant financial relationships to disclose.
Study on external Chinese herbal medicine LC07 treating capecitabine-induced hand-foot syndrome in metastatic breast cancer
Authors: Jia L. , Lou Y. , Tan H. 
Published: August 2020

1088 Background: With the capecitabine being increasingly used in the treatment of metastatic breast cancer (MBC), the common side effect of capecitabine, hand-foot syndrome (HFS) has become a main problem which can distress both physicians and patients. Severe HFS such as severe pain can have a negative impact on quality of life (QOL) of these patients and cause reduced dosage or even stopping chemotherapy. No effective treatment for HFS can be available at present. Over the years we have used LC07, a kind of external agents from Chinese herbs (Herba Geranii, etc.), to treat capecitabine-induced HFS. In this study, the efficacy and safety of LC07 were evaluated in patients with MBC and HSF. Methods: Eligible patients includes patients with MBC, who had HFS (NCI-CTC grade ≥1) after receiving single capecitabine chemotherapy (1,250 mg/m2, PO, twice daily, cycled days 1–14, every 21 days). LC07 granules 10g was dissolved in 1,000mL of warm water (keep 34°C-37°C in a footbath), the patients soaked their feet and hands in this lotion for 20 minutes, twice daily for 7 days. An independent researcher assessed symptoms before and after treatment. Evaluation criteria, CR as symptom disappearing completely, PR as NCI-CTC grade for HFS decreasing by more than 1 level after treatment, the total response rate as CR+PR. The QOL of these patients were also evaluated before and after treatment using a FACT-B questionnaire (Version 4.0-Chinese). Results: 42 patients (pts) have been enrolled in this study. All of them are Asian and female. Media age 51.5 yrs (25–72). Grade 1 for HFS was seen in 8 pts, G2 in 19 pts, and G3 in 15 pts. The total response rate was 83.3% (35/42), CR 38.1% (16/42), PR 45.2% (19/42). The average time from therapy to pain relief was 1.8±0.8 days, the skin lesion of HFS including dermatitis, peeling, ulceration have been improved after treatment. The QOL scores before and after treatment were 77.24±25.69 and 109.17±20.53, respectively (p < 0.01). No side effects such as skin allergies related to LC07 was found in this study. Conclusions: In the treatment of capecitabine-induced HFS, the external Chinese medicine LC07 is fast effective for relieving pain, and it has the features of easy use and no skin allergies. Thus LC07 can improve the QOL of patients with MBC and HFS. No significant financial relationships to disclose.