bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary results of docetaxel (T) and trastuzumab (H) combination administered every 21 days in metastatic breast cancer (MBC) and HER-2 over-expression patients (P)
Authors: Tusquets I. , Ramos M. , Gil M. , Sánchez-Rovira P. , Mel J. R. , Duque A. , García-Estévez L. , Velasco A. 
Published: March 2020

10670 Background: T combined with weekly H confers greater tumor response and survival compared to T monotherapy in P with Her-2 positive MBC. A recent report has demonstrated that H can be administered q3wks. The primary endpoint is to evaluate time to progression (TTP). Sencondary objectives are response rate, overall survival and safety profile. Methods: P cytologically or histologically confirmed of metastatic breast cancer, HER-2 positive (+++ by Herceptest, or FISH positive), age > 18, ECOG PS ≤ 2, and adequate organ function, were included. Prior chemotherapy for MBC or adjuvant anthracycline-based regimen in the previous 6 months was not allowed. Treatment: T 100 mg/m2 iv D1 q3wks for 6 cycles, H 8 mg/kg (cycle 1) and 6 mg/kg (consecutive cycles) iv D1, q3wks. P may receive H monotherapy until PD at the investigator criteria. Results: Over 41 analyzed P, median age was 57 years (29–75); ECOG PS 0–1 95% and ductal carcinoma 88%. Twenty five P received prior chemotherapy. Treatment: 217 cycles of TH (median 6) were administered. After that, 23 P received 189 cycles of H monotherapy (median 5, 1–32). During TH treatment median RDI was 97% for T and 96% for H, and it was 99% during H treatment. Over 33 P for efficacy analysis (2 consent withdrawal, 1 allergic reaction, 1 ongoing and 4 response not confirmed by RECIST criteria), 6 achieved CR and 12 PR, for an ORR of 54.6% (95% CI: 37.6–71.6). Median follow-up time was 11.8 m and median TTP was 8.8 m (95% CI, 1.9–15.6). All P were evaluable for safety. During TH treatment, grade III/IV neutropenia occurred in 16 cycles (7.4 %), 14 of them were febrile neutropenia episodes (6.5%). Other grade III/IV toxicities per cycle were: leucopenia (5.5%), hyperglycemia (2.3%), anorexia (2.3%) and skin (2.3%). During H monotherapy treatment, the only grade III-IV toxicities observed were, skin (1.6%), oedema (1.1%), nail disorders (0.5%) and malaise (4.3%). Six P (14.6%) dropped out due to cardiac toxicity: 5 had LVEF under 50% and one atrial fibrillation. Conclusions: Preliminary results suggest that TH q3wks followed by H as single agent, is an effective regimen for the treatment of P with Her2 positive MBC. No significant financial relationships to disclose.
Exemestane (Exe) as primary treatment in hormonosensible early breast cancer of the elderly: Preliminary results of a phase II multicenter open Italian study
Authors: Mustacchi G. , Mansutti M. , Barni S. , Cazzaniga M. E. , Farris A. , Ceccherini R. , Sacco C. , Dellach C. 
Published: March 2020

10689 Background: In the late 90s two large phase III trials (GRETA & CRC) showed that tamoxifen as sole treatment was a possible alternative to surgery in old women. Two Phase III neoadjuvant trials showed recently that letrozole is superior and anastrozole is not inferior to tamoxifen.A few phase II and a small fase III trials showed interesting results also with the steroidal inactivator exemestane. Methods: We are running a fase II open trial in early breast cancer patients aged over 70 with receptor rich tumors, treated with exemestane 25 mgs/day for 6 months before surgery. Primary endpoints are clinical response, breast conservative surgery (BCS) rate and safety. Results: Of the planned 100 patients we report preliminary results on 50 patients (mean age 81 , range 70–92) evaluable for clinical and mammographic response. 33/50 had a partial response (66%), 2/50 PD on treatment. Clinical basal mean size of tumors was 4.4 cms (4,81 in responders) and 2,67 cms the final in responders patients. Eight patients refused surgery, 12 are too early, 23/30 underwent BCS where 17 of them (74%) were unfit for BCS at basal evaluation. No remarcable exemestane related toxicity was recorded. Conclusions: As expected from published data of phase III trials in metastatic and adjuvant setting, exemestane appears to be very active also in the neoadjuvant setting. Probably there is no more need of large phase III trials in order to consider exemestane in the preoperative setting in rich receptor tumors. In old and frail patients this could also be considered as sole treatment. [Table: see text]
Patterns of adjuvant hormonal therapy (AHT) usage in early stage breast cancer (ESBC)
Authors: Cobb P. , Schwartzberg L. S. , Kulig K. , Johns A. , Fortner B. 
Published: March 2020

10695 Background: Aromatase inhibitors (AIs) are recommended as first line agents or after tamoxifen (T) as extended adjuvant therapy in hormone receptor positive ESBC. Little is known about adherence, adverse events, toxicity, duration of therapy, or change in agents in the community setting. Disparities between actual usage and clinical guideline recommendations could have a significant impact on outcomes. Methods: This retrospective observational study reviewed charts of 200 ESBC patients (pts) receiving AHT from 4 US community oncology clinics. To be eligible, each patient must have completed >1 patient care monitor (PCM) survey, a validated electronic self-report measure that produces indices related to physical symptoms, psychological symptoms, functional status and overall health-related QOL. Baseline symptoms and toxicities prior to initiation of AHT and during and/or after are available on all evaluable patients. Pt charts were identified consecutively in reverse chronological order starting from 3/01/05. Results: Data are available on 42 pts. The mean age of the patients was 63.6 (range 43–86). First line AHT was T in 24 and AI in 18. Of available AIs, 14 pts received anastrozole, 3 letrozole and 1 exemestane. 18 pts continue AHT as per guidelines and 7 completed planned therapy (median duration, 58.8 months). Switching from 1st line AHT to another agent occurred in 13 pts; 10 switched from TAM to an AI, mean duration of TAM 31.0 months and 3 pts to another AI. 8 pts (19%) changed for an adverse event (AE), and 5 changed due to MD/pt preference. AEs included eye problems (2), weight changes (2), GYN complaints (2), vasomotor symptoms (1), muscle/joint aches (2), and increased alkaline phosphatase (1). Of pts receiving 2nd line AHT, 4 had discontinuation for an AE: muscle/joint aches (2), vasomotor symptoms (1), and eye problems (1). Conclusion: Switching of first line AHT is common for reasons of AEs or MD/pt decision. Pts with AEs to AHT often experience additional AEs after exposure to another agent. [Table: see text]
Gemcitabine and docetaxel for metastatic breast cancer—Further data
Authors: Laufman L. R. , Spiridonidis C. H. , Parker T. , Boury P. , Maggard V. , Miller S. 
Published: March 2020

10704 Background: A previous study with weekly gemcitabine and monthly docetaxel at 100 mg/m2 yielded a 79% response rate and a median survival of 24 months. (Laufman, Ann Oncology 2001; 12:1–6). This study was designed to see if the efficacy to toxicity ratio could be improved by decreasing the docetaxel dose to 75 mg/m2. Methods: Gemcitabine and docetaxel were given to 25 patients, all of whom had received prior chemotherapy. Nine had had taxanes, more than 12 months before entry. A maximum of 6 cycles of gemcitabine 800 mg/m2 on days 1, 8 and 15 and docetaxel 75 mg/m2 on day 1 were given every 28 days. Prophylactic antibiotics were given during neutropenia. Growth factors were used for anemia, neutropenia, or for secondary neutropenic prophylaxis. Maintenance therapy consisting of gemcitabine 800 mg/m2 on days 1, 8 and 15 every 28 days was given to 12 patients, 2 of whom also received consolidation radiation. Results: A total of 122 cycles of induction therapy were given, with 14 patients receiving all 6. Dose delivery was 91.9% for docetaxel and 70.2% for gemcitabine. A total of 43 maintenance cycles were given, ranging from 1 to 12 cycles per patient. Dose delivery was 70.6%. Toxicity consisted of myelosuppression and fatigue. Grade 4 neutropenia occurred in 20 patients but was complicated by infection or fever in only 3. Five patients had grade 3 anemia and 4 had grade 3 thrombocytopenia. Other grade 3 toxicities consisted of fatigue in 8 patients, myalgia/arthralgias in 4, mucositis in 1, pneumonia in 1 and diarrhea in 1. Responses defined by RECIST criteria occurred in 12 patients (48%), including 8 of 16 taxane-naïve and 4 of 9 taxane-exposed patients. Conclusion: This regimen is active, and the most common toxicity is asymptomatic neutropenia. Sponsored by Eli Lilly and Aventis. No significant financial relationships to disclose.
Prevention of febrile neutropenia by prophylactic use of G-CSF with adjuvant TAC based on risk assessment—Single institute study
Authors: Chellama M. K. , Awadhi S. A. , Vyas V. , Nemec J. , Khodary A. , Enezi F. , Delvadiya M. D. 
Published: March 2020

10711 Background: TAC confers significant disease free and overall survival benefits vs FAC for patients with node positive breast cancer. However TAC is associated with higher incidence of febrile neutropenia. In our study prophylactic G-CSF was used in patients, who developed grade 4 neutropenia with ANC < 100 or febrile neutropenia to prior cycle of TAC. Methods: Following surgery, patients with operable, 1–9 nodes positive breast cancer, ECOG 0–1, and adequate hematologic and organ function were enrolled on to the study, and were to receive TAC day 1 every 3 weeks for 6 cycles . All patients received prophylactic Ciprofloxacin 500-mg bid from days 5–14 after each cycle of chemotherapy unless prophylactic G-CSF was given. Eighty three patients were enrolled during the period 13–1-04 to 30–12–05. Patients who had received at least 2 cycles of TAC were eligible for evaluation. Patients were given prophylactic G-CSF if they had profound neutropenia (ANC < 100) or febrile neutropenia in prior cycle. Results: At the cut-off date for this analysis 79 patients were evaluable. 68 patients had completed the planned 6 cycles of TAC. Three, 2, 3 and 3 patients completed 2, 3, 4 and 5 cycles respectively. Sixty one patients required prophylactic G-CSF - 21 after febrile neutropenia in prior cycle, 39 after profound neutropenia in prior cycle and 1 received from first cycle itself because of post operative seroma with diabetes mellitus. 23 patients developed febrile neutropenia (29.1%) - 3, 8, and 12 after 3, 2 and 1 cycles respectively. Only two patients (3.2%) who received prophylactic G-CSF developed febrile neutropenia. Full dose of TAC could be maintained in 98.6% cycles. Conclusions: The use of G-CSF prophylaxis based on risk assessment could prevent febrile neutropenia in patients, who had profound neutropenia in prior cycle. Also G-CSF could prevent further febrile neutropenia in patients who had developed the same in prior cycle. The above strategy helped in maintaining the dose intensity of TAC. No significant financial relationships to disclose.
Phase II pilot trial of imatinib mesylate with weekly docetaxel in metastatic breast cancer
Authors: Barton J. H. , Liggett W. , Mainwaring M. , Hainsworth J. D. , Simons L. , Spigel D. R. , Burris III H. A. , Yardley D. A. 
Published: March 2020

10716 Background: Overexpression of platelet derived growth factor receptor (PDGFR) has been associated with breast cancer tumor progression and may serve as a potential target for therapy. Inhibition of PDGFR signaling in tumor stroma represents a novel strategy that has demonstrated enhanced chemotherapy antitumor effects, decreased tumor interstitial fluid pressure as well as increased tumor transcapillary transport. Imatinib mesylate (G) is a potent PDGFR tyrosine kinase antagonist. This phase II pilot study evaluates the feasibility, toxicity, and efficacy of imatinib administered with docetaxel as a strategy to enhance docetaxel’s chemotherapeutic effects in metastatic breast cancer (MBC). Methods: Eligibility requirements: 0–1 prior regimens for MBC, > 6 months from prior adjuvant taxanes, RECIST measurable disease, ECOG PS 0–2, adequate organ function, < G2 neuropathy. Treatment: docetaxel 30 mg/m2 IV weekly 3 of 4 weeks. Imatinib mesylate 600 mg po QD. Pts were evaluated for response every 8 weeks; treatment continued until progression or toxicity. Results: 7 pts have been enrolled to date. Median age is 61, all with ECOG PS 0. 5 pts received prior adjuvant therapy; 2 pts received prior taxanes. 43% received prior hormonal therapy. Only 1 pt was ER+/PR+. Hematologic toxicity was mild, consisting only of G3/4 anemia in 2 pts and G3 thrombocytopenia in 1. No febrile neutropenia was noted. Nonhematologic toxicity was characterized primarily by G3 GI toxicity: 4 pts diarrhea, 3 N, V, 1 anorexia, 1 abdominal pain. This was attributed to imatinib in all but 1 pt, in whom both drugs were implicated. 2 pts were removed from treatment and 3 pts required dose reductions, all due to GI toxicity consisting of N, V, and diarrhea. 3 pts experienced dose interruptions and 2 pts exhibited disease progression. Conclusion: These early preliminary results demonstrate imatinib mesylate, in combination with weekly docetaxel as a strategy to inhibit breast cancer PDGFR signaling, is feasible. GI toxicity with this combination was prominent and warrants dose modifications. Updated toxicity and efficacy data will be presented. [Table: see text]
Phase II study of pegylated liposomal doxorubicin plus vinorelbine in metastatic breast cancer
Authors: Del Prete S. , Montella L. , Faiola V. , Guarrasi R. , Busto G. , Addeo R. 
Published: March 2020

10718 Background: Pegylated liposomal doxorubicin and vinorelbine are active single agents in metastatic breast cancer (MBC) and lack overlapping toxicity. The possibility of combining these two drugs therefore seems attractive. Methods: Twenty-five patients with MBC entered a phase II study of pegylated liposomal doxorubicin 40 mg/m2 intravenously (i.v.) on day 1 plus vinorelbine 25 mg/m2 i.v. on day 1 and vinorelbine 60 mg/m2 oral on day 14, every 4 weeks. A two-staged Simon accrual design was adopted for this phase II trial. Patients were required to have measurable disease, previous chemotherapy with or without an anthracycline-containing regimen, and a normal left ventricular ejection fraction (LVEF). Results: Twenty-one patients with MBC were eligible, assessable for response and toxicity. The overall response rate (on an intent-to-treat basis) was 36% (9 of 25; 95% CI, 20%-54%). One complete response and 8 partial responses were noted. In addition, 11 patients (44%) had stable disease of > 4 months duration, and 5 patients (20 %) had disease progression. Median time to disease progression was 10 months (range, 3–38 months) and median overall survival was 15 months (range, 4 to > 62 months). Neutropenia was the most frequent toxicity (grade 4 in 30% of patients and 19% of cycles), but neutropenic fever was seen in only 3 cases. No septic deaths occurred. Nonhematologic grade 3 side effects included skin toxicity (palmar-plantar erythrodysesthesia syndrome, 8%) and mucositis (14%). Late alopecia was seen in 51% of patients (grade 1 in 39%, and grade 2 in 12%). The median LVEFs were 64% (range, 50%-81%) at baseline and 62% (range, 37%-70%) after treatment. Only one patient presented an LVEF decrease to < 50%; however, no clinical heart failure was noted, and this patient recovered normal values after cessation of therapy. Conclusions: The combination of pegylated liposomal doxorubicin and vinorelbine can be safely administered to patients with anthracycline-pretreated MBC and is active in this population. Final data analysis will be presented. No significant financial relationships to disclose.
Efficacy and safety of mitoxantrone-based chemotherapy as adjuvant treatment in elderly patients (EP) with node positive and high risk node negative breast cancer (BC)
Authors: Fedele P. , Rizzo P. , Cusmai A. , D’Amico M. , Chetrì M. C. 
Published: March 2020

10738 Background: Breast cancer is a very frequent malignancy among EP. Adjuvant chemotherapy improves survival for patients with early breast cancer, but older woman at high risk of recurrence are frequently not offered adjuvant chemotherapy and few data are available on efficacy, compliance and safety of adjuvant chemotherapy when indicated in EP. Objective: the aim of our study was to determine the efficacy, compliance and safety of adjuvant mitoxantone-based chemotherapy (FNC) in high risk BC patients older than 70. Methods and Results: From July 1994 to July 2005 we treated 30 patients >70 years, who had diagnosed with early BC in our institution. The treatment (mitoxantrone 10 mg/m2, 5-Fluorouracil 600 mg/m2, Cyclophosphamide 600 mg/m2, i.v. on day 1 every 3 weeks for 6 cycles) was indicated if patients had no severe comorbidity and a high risk of recurrence. All the patients had undergone mastectomy (56%) or quadrantectomy plus axillary lymphadenectomy (44%). Patients undergoing conservative surgery were scheduled for radiotherapy that was planned immediately after the end of chemotherapy. Study population age ranged from 70–78 years, mean age of 74 years.PS (ECOG) was 0 in 74% of patients, 1 in 26%. Comorbid conditions were detected in 38% of patients (64% hypertension, 8% arythmia, 10% depression syndrome, 14% arthrosis) Main histologic types were invasive ductal carcinoma (87%) and lobular carcinoma (13%). Stage was IIA in 20%, IIB in 37%, IIIA in 43%. Grading was 2 in 51%, G3 in 49%.Sixty-seven percent of tumors were ER+ PGR+, 20% were ER- PGR-, 8% ER-PGR+, 5% ER+ PGR-. Seventy-five percent of patients received adjuvant endocrine therapy, after the end of chemotherapy. Toxicity was very manageable with grade 3–4 haematological toxicity in 1 patient, nausea and vomiting appeared as grade 0 and 1 severity in 10%, alopecia was extremely mild and appeared as grade 0 and 1 in 12%. Only 1 patient disrupted treatment because of toxicity. The overall and relapse free survival rates were 70% and 73% at the 60-month follow up, respectively. Conclusion: FNC is an effective and well-tolerated combination regimen suitable as adjuvant chemotherapy for high risk breast cancer EP. No significant financial relationships to disclose.
Trastuzumab in combination with bevacizumab in advanced breast cancer patient resistant to chemotherapy
Authors: Ordonez J. , Gomez Martin C. , Cortes-Funes H. 
Published: March 2020

10762 Background: HER2 positive is associated with up-regulation of VEGF in human breast cancer cells. Superior efficacy was observed if anti-HER2 antibody (trastuzumab) (TZB) is given with anti-VEGF antibody (bevacizumab) (BVB) in xenografs models (Konecny G., 2004). In one phase I study with 9 patients (pt), the combination TZB+BVB was well tolerated without important toxicity, achieving 1 complete response and 4 partial responses (Pegram M, 2005). Methods and Result: We report a clinical case of a 48 years old woman with an advanced resistant breast cancer diagnosed in 1995 and treated with radical surgery for a invasive ductal carcinoma pT2N1M0 HHRR - and c-erbB2 positive (+++). She received adjuvant CMF for 6 cycles and local radiotherapy (XRT). In 2000, lung and liver metastases (mts) with increased CA 15.3 serum levels and was treated with paclitaxel + TZB achieving complete response. Maintenance with TZB was given for one additional year. In 2002, bone and brain mts with increase of CA 15.3 and was treated with vinorelbine + TZB with whole brain irradiation. On March 2005, bone and liver progression was treated with capecitabine + TZB and pelvic XRT with control of the mts. On August, pt developed rapid progression of liver mts with intensive abdominal pain requiring high doses of morphine; progressive jaundice (total bilirubin: 24.4 mg/dl) and low performance status. The level of CA 15.3 was 626 U/ml. We decide treatment with TZB + BVB in a biweekly schedule for 6 consecutive weeks. Whole liver XRT was given in two weeks (15.5Gy). The treatment was well tolerated and the pt improves immediately her clinical situation. Levels of CA 15.3 dropped to 161 U/ml and bilirubin to 4.87 mg/dl. The pt continues the treatment in ambulatory regiment for 7 additional weeks. She had a pathological hip fracture at home and was admitted to the Hospital developing an acute lung tromboembolism dying suddenly. Liver metastases still in clinical and biochemical response. Conclusions: The combination of TZB with BVB could be an effective alternative treatment for pt with advanced and resistant breast cancer, erbB2 positive, and need to be explored in clinical trials. No significant financial relationships to disclose.
Gene expression profiling of circulating tumor cells from breast cancer patients
Authors: Magbanua M. M. , Lang J. E. , Scott J. , Crothers J. R. , Federman S. , Haqq C. , Park J. 
Published: March 2020

10769 Background: Levels of circulating tumor cells (CTC) have prognostic and predictive significance in metastatic breast cancer. However, since CTCs are extremely rare, little is known about the actual phenotype of these cells. In order to characterize these cells, we performed cDNA microarray analyses of CTC isolated from peripheral blood (PB) of breast cancer patients. Methods: CTCs were directly isolated via immunomagnetic enrichment (IE) followed by fluorescence activated cell sorting (FACS). Total RNA was then subjected to two rounds of linear amplification and hybridized to cDNA microarrays (∼40,000 cDNAs). Validation studies used spiked BT474 cells. Clinical studies used PB (10–20 ml) from patients with metastatic breast cancer. Results: Rare spiked tumor cells (e.g., 320 cells in 10 mL PB) were efficiently recovered by IE/FACS (50% yield). Expression profiles of recovered cells, both by TaqMan of a 37 gene panel as well as by global gene expression analysis, matched that of BT474 cells in culture. In contrast, these profiles were clearly distinct from that of normal PB, ruling out significant contamination from blood elements. In clinical studies, IE/FACS isolated small numbers of CTCs (10–1000 cells). Expression profiles of CTCs were compared to that of normal blood, primary breast tumors, and normal epithelial samples. Unsupervised hierarchical clustering revealed that CTC profiles were readily distinguished from that of normal blood and normal epithelium; and further analysis revealed that CTC cluster with a subset of primary breast tumors, particularly the basal-like phenotype. Candidate genes associated with the CTC phenotype were also identified. Conclusions: We have developed and validated a method to isolate rare CTCs and profile them via cDNA microarray analysis. In addition, our gene expression analyses of CTC further provide evidence to the malignant nature of these cells. Further expression profiling of CTC may yield insights into their phenotype, pathophysiology and potential as biomarkers. [Table: see text]