bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docetaxel and capecitabine as first-line chemotherapy in patients with advanced breast cancer
Authors: Gennatas C. , Michalaki V. , Psychogios J. , Gennatas S. , Kondi-Paphiti A. , Karvounis E. , Kairi E. 
Published: March 2020

10734 Background: Capecitabine (C) and Docetaxel (D) have demonstrated synergy in both preclinical and clinical studies in metastatic breast cancer (MBC). The aim of the study was to evaluate the activity and tolerability of the combination of CD as a first -line therapy for patients with advanced breast cancer. Methods: Thirty- five patients have been enrolled in the study. Median age was 54 years (range 35–73). ECOG PS was of 0–2 (PS 0: 6 patients, PS 1: 5 patients, PS 2: 14 patients), All patients were Her-2 neu negative. Patients received Docetaxel 75 mg/m2 on day 1, with routine pre and post-medication with steroids, and Capecitabine 950 mg/m2 p.o. bid on days 1–14, every 3 weeks until disease progression or unacceptable toxicity. Results: A total of 233 cycles were given with a median of 7 (2–12). Of the 35 evaluable patients, 17 patients (48%) achieved partial response (PR) and 6 patients (17%) attained stable disease (SD). The median duration of response was 12 weeks and the median duration of SD was 20 weeks. The median time to progression (TTP) was 28 weeks. The median overall survival was 90 weeks. All patients were evaluable for toxicity. Toxicity was mainly hematological with G3 or 4 neutropenia in 7 patients (20%). Febrile neutropenia was not encountered. There was not significant GI toxicity. Conclusions: Combination chemotherapy with Capecitabine and Docetaxel shows promising efficacy as first- line therapy in advanced breast cancer with an acceptable toxicity profile. No significant financial relationships to disclose.
Limited impact of tamoxifen following dose-intensive L-FAC multimodality therapy of breast cancer
Authors: Jabboury K. W. , Wong A. , Sexton K. , Rogers L. , King K. , Reilly C. , Thomas S. , Curtis P. , Mangini O. , Behar R. 
Published: March 2020

10741 Background: Front-line dose-intensive L-FAC has demonstrated a favorable 5-year relapse free survival pattern (ASCO 2004 #739). Tamoxifen was given for 5 years to ER+ patients after L-FAC completion. We evaluated the impact of adding tamoxifen to L-FAC. By design, this pilot study excluded low-risk patients not candidates for chemotherapy. Methods: 109 breast cancer patients were enrolled (4 excluded due to treatment violations) from 6/1989 to 1/2003: 20 Stage I (S), 52 S-II, 22 S-III, for a total of 94 patients. 11 S-IV patients were excluded from survival analysis. Adverse tumor presentations included: ER- 49, PgR- 60, P53+ 24, non-diploid 39, histological grade III 37, CerbB2+ 33. L-FAC included 72 hour (h) iv infusion 400mg/m2/day (d) 5-fluorouracil (F) modulated by iv bolus 200mg/m2/d X3 leucovorin (L), concomitantly with 24h iv d1 600–1000mg/m2 cyclophosphamide (C), 48h iv d2 + d3 60mg/m2 doxorubicin (A). S-I and S-II were given 6 courses and 8 for S-III. Increasing A + C dose level and/or shortening treatment intervals < 3 weeks with growth factors provided intensification. 40 patients received tamoxifen. Results: At a median follow-up of 74 months (range 9–214), 73 (78%) are alive (1 with relapse). Relapse free survival was: S-I 95%, S-II 81%, S-III 78%. At average course intervals of 18 days, dose intensity A/C mg/m2/wk was 24.2 / 335.4 with evidence of WHO grade III/IV stomatitis in 43%, neutropenia 59%, cumulative thrombocytopenia 50%, hand-foot syndrome 32% of patients. Aside from delayed relapse associated with tamoxifen, relapse-free survival >82 months was similar with and without tamoxifen. No relapse was observed after >53 months in ER- tumors despite showing higher frequency of adverse tumor risk factors. Conclusion: The impact of adding tamoxifen appears quite limited in a patient population with adverse tumor presentation treated with dose-intensive L-FAC. No significant financial relationships to disclose.
An intraoperative sentinel lymph node identification in breast cancer patients guided by near-infrared fluorescence imaging: Preliminary results
Authors: Tagaya N. , Yamazaki R. , Nakagawa A. , Mori S. , Hamada K. , Kubota K. 
Published: March 2020

10776 Background: Recently, radioactive tracer, a vital dye, or a combination of both has been applied to detect intraoperative sentinel lymph nodes (SLN) in early breast cancers. In this study, we present a novel method in SLN identification that provides with high detection and low false-negative rates. Methods: This study enrolled 19 patients with a tumor less than 3 cm in diameter. Their mean age was 49.6 years. Preoperative TNM stage was I in 13 cases, IIa in 4, and IIb in 2, respectively. Initially the combination dye of indocyanine green and indigocarmine was injected subdermally in the areolar. Fluorescence imaging (photodynamic eye: Hamamatsu Photonics Co.) was obtained using a charge coupled device camera with a cut filter as the detector, and light emitting diodes at 760 nm as the light source. Subcutaneous lymphatic channels draining from the areola to the axilla or other directions were visible by fluorescence imagings immediately. After incising the axillary skin on the disappeared point of fluorescence image, SLN was then dissected under the guidance of fluorescence. Results: In all patient, lymphatic channels and SLN were successfully visualized. SLN was observed before skin incision in two patients. The number of fluorescence SLN ranged from 2 to 11 (mean: 5.5) and blue dyed SLN ranged from o to 6 (mean: 2.3). In the latter, SLN was not identified in one patient. Six patients had lymph node metastases pathologically. All of them were recognized by fluorescence imagings, however, in two patients LN with metastasis were not identified by a vital dye. There were no intra- or postoperative complications associated with SLN identification. Conclusions: This method is feasible and safe to detect SLN intraoperatively with less invasive, real-time observation and no requirement of training. We hope that this method will provide with high detection and low false-negative rates in SLN navigation surgery. No significant financial relationships to disclose.
A phase II study of docetaxel-carboplatin as first line therapy in the patients with visceral metastatic breast cancer: A Bangladesh experience
Authors: Reza M. S. , Chowdhury Q. , Hai M. A. , Rahman M. A. 
Published: March 2020

10792 Background: Metastatic breast cancer is heterogeneous and treatment decisions are influenced by multiple factors. Docetaxel remains as the standard chemotherapy agent in the management of metastatic breast cancer. We conducted a phase II study to examine the efficacy and tolerability of docetaxel with carboplatin in the treatment of visceral metastatic breast cancer patients. Methods: From July 2000 to December 2004, 32 patients with; histologically/cytologically proven, bidimensionally measurable visceral (pulmonary & hepatic) metastatic breast cancer, age 18–75 years with ECOG performance status 0–3, no prior chemotherapy, life expectancy > 3 months, adequate bone marrow, renal, hepatic and hematological values were enrolled. It was an open-labeled, non-randomized, single-centered and prospective study. The patients received docetaxel (75 mg/m2) and carboplatin AUC 5 on day 1 at an interval of 3 weeks. Outcome measures were response rates and tolerability was measured by adverse events and laboratory blood values. Results: This study consisted of 30 female and only 2 male patients. Median age was 55 years. 18 patients (56.25%) were presented with pulmonary metastases, where as there were 12 patients (66.67%) with single lung and the remaining 6 patients (33.34%) with bilateral lung metastases.14 patients (43.75%) had hepatic metastases. In total, 168 cycles chemotherapy were administered with a median of 5.25 cycles per patient, and 29/32 patients were evaluable for responses. The overall response was 62.07% with 8 complete responses and 10 partial responses. 6 patients (20.69%) had stable disease and only 5 patients (17.24%) had progressive disease. Grade 3 hematological toxicities were observed as follows: neutropenia (24%) and anemia (15.6%). Some non-hematological toxicities (including nausea, vomiting, fluid retention and peripheral neuropathy) in 15 patients (51.72%) were observed. No severe febrile neutropenia and no fatal events were observed. Conclusions: This phase II study supports the use of docetaxel-carboplatin combination in chemo naïve visceral metastatic breast cancer patients due to its very promising effects with well tolerated toxicities in Bangladeshi population. No significant financial relationships to disclose.
Phase I analysis of systemic interferon alpha utilized with gliadel in adults with recurrent glioblastoma multiforme (GBM)
Authors: Lawson D. H. , Phuphanich S. , McKenzie E. , Greiner K. , Shires K. , Olson J. J. 
Published: March 2020

11508 Background: Local therapy with Gliadel was found to increases median survival at recurrence from 23 to 31 weeks when compared to placebo wafers. Brain tumor specimens have been observed to have a 40–50% rate of deletion of the IFNα interferon a gene. Previous clinical studies have demonstrated response rates to IFN-α in the range of 0–41% in the treatment of recurrent primary malignant glioma, either alone, or in combination with other modalities. This study assess the safety and toxicity of Interferon α-2b (IFN-α) and 3.85% BCNU-permeated wafers (Gliadel®). Methods: This is a phase I dose escalation assessment of the toxicity of IFN-α utilized in conjunction with Gliadel® in patients with recurrent GBM, who failed previous radiation and chemotherapy. Ten patients were enrolled in this dose escalation trial. Three dose levels were studied were with the starting dosage of was IFN-α 3 Mu/m2 (n = 3), 6 Mu/m2 (n = 3) and 9 Mu/m2 (n = 4) subcutaneously injection 3 times a week for a total period of 8 weeks with the first dose being initiated 1 week following craniotomy and Gliadel placement. Results: There were 10 patients, 5 males and 5 females with a median age of 46 yrs (range 35–55). At re-operation, all histology revealed 10 GBM. At dose 3 Mu/m2, 2/3 pts developed grade 2 fatigue, myalgia and depression, but completed treatment with 1 PR (109 + wks) and 1 CR (91 + wks) and 1 PD (6 wks). Another patient was off study because of progressive disease (PD). At dose 6 Mu/m2, all 3 had PD with 2 pts having Grade 2 received a dose reduction because of diarrhea and 1 patient withdrawing early for PD finished only 1 cycle (4 wks). At dose 9 Mu/m2, 2 patients developed grade 3 toxicity fatigue/malaise and one patient completed therapy with dose reduction and but progressed, another patient stopped treatment after first 3 doses due to progression. There were overall response of 20% (1 PR and 1 CR) with duration of 109+ and 91+ wks. Clinical response with IFNα gene is being analyzed. Conclusions: This study defined MTD at 6 Mu/m2 with a DLT at 9 Mu/m2 and recommended a Phase II dose in this population. Since interestingly, the responses occurred at the lowest dose, suggesting a portion of the effect may be anti-angiogenic in nature. No significant financial relationships to disclose.
Radiosurgery for pituitary adenomas: Evaluation of its efficay and safety
Authors: Salvajoli Sr. J. V. , Castro D. G. , Cecílio S. A. , Canteras M. M. 
Published: March 2020

11515 Background: Pituitary adenomas account for approximately 15% of all primary brain tumors. Multimodality treatment is often necessary and options include medical management, microsurgery, radiotherapy and radiosurgery (RS). Recently, RS has gained acceptance as a complementary treatment since it has been associated with a shorter latency for its effects and lesser morbidity than that of radiotherapy. The objective of this study was to assess the effects of RS on the radiological and hormonal control and its toxicity in the treatment of pituitary adenomas. Methods: It was done a retrospective analysis of the first 26 consecutive patients with pituitary adenomas treated with RS at our institution between 1999 and 2004. RS was delivered with a multiheaded cobalt unit (Gamma Knife). The median radiation dose was 20 Gy defined to the 50% isodose line. Almost 20% of tumors were non-secretory. The remaining were prolactinomas (31%), adrenocorticotropic hormone-secreting (34%) and growth hormone-secreting tumors (15%). Hormonal control was defined as hormonal response (decline of more than 50% from the pre-RS levels) and hormonal normalization. Radiological control was defined as stasis and shrinkage of the tumor. Hypopituitarism and visual deficit were the morbidity outcomes. Hypopituitarism was defined as the initiation of any hormone replacement therapy and visual deficit as loss of visual acuity or visual field after RS. Results: The median follow-up was 40,8 months.Tumor growth was controlled in 96% of the cases and tumor shrinkage ocurred in 8% of the cases. Hormonal control was observed in 14 of 20 (70%) and hormonal normalization in 7 of 20 (35%) patients after RS, with a median latency period of 28,2 months. The 3-year actuarial rate of hormonal control and normalization were 51% and 47,6%, respectively, and the 5-year actuarial rate were 74% and 68,6%, respectively. There were no patients with visual deficit or hypopituitarism after RS. Conclusions: RS is an effective and safe therapeutic option in the management of selected patients with pituitary adenomas. The short latency of the radiation response, the highly acceptable radiological and hormonal control and absence of complications at this early follow-up are consistent with literature. No significant financial relationships to disclose.
The influence of rest primary brain tumours on disease free and overall survival
Authors: Scepanovic D. D. , Bajic N. D. 
Published: March 2020

11529 Background: We analysed the influence of rest primary brain tumours on disease free survival (DFS) and overall survival (OS). Methods: From 1998 till 2004, 80 patients (pts) with primary brain tumours were treated with postoperative radiotherapy (RT). The male–female ratio was 44 versus (vs) 36 pts (55% vs 45%). The median age was 50 years (yrs) (min 17, max 79 yrs). Performance status was 90–100% in 30 pts, 80–90% in 39 pts and 70–80% in 11 pts. Low grade astrocytoma was reported in 13 pts, anaplastic astrocytoma and glioblastoma in 49 pts, low grade oligodendroglioma in 2 pts, meningeoma in 9 pts and others in 7 pts. The postoperative RT dose was 50 Gy in 20 pts while 60 pts was treated with dose above 50 Gy, 2 Gy per day, 5 fractions per week, linear accelerator X rays, 6 MeV energy. We analysed two groups of pts (50 pts had rest tumours after surgery and RT within 6 months (mo) of operation and 30 pts without rest tumours). We analysed the influence of age, pts ambulatory, corticosteroids therapy during RT, pathohystological diagnoses (PH), RT doses and chemotherapy (CT) application (carmustine, 80 mg/m2, i.v. 1–3 days after 6 weeks of RT completion) on DFS and OS. Results: The median follow up time was 16 mo (min 6, max 96 mo). Thirty pts (37.5%) is still alive while 50 pts (62.5%) died. Cox regression model gave us data of influence on DFS in this way: cortocosteroids therapy during RT, CT application, RT dose and furthermore on OS: age, pts ambulatory, PH report and RT dose. Logistic regression model gave us data for rest tumours group of pts (50 pts) to be the greatest influence on survival patients ambulatory and corticosteroids therapy during RT. Between two groups of pts there is statistically significant difference on DFS and OS (p < 0.001). 1 yrs DFS was 30% and 2 yrs DFS was found in 26% of pts while 1 yrs OS was 44% and 2 yrs OS was 42% of pts. Conclusions: Pts with rest tumours especially anaplastic astrocytoma and glioblastoma have a shorter life span. However, RT dose does influence DFS and OS in pts with good performance status. No significant financial relationships to disclose.
Potent cytotoxicity and inhibition of pan-cell cycle progression by Alchemix, a novel alkylating anthraquinone
Authors: Epenetos A. A. , Pors K. , Smith P. J. , Patterson L. H. 
Published: March 2020

12030 Introduction: DNA topoisomerase II (topo II) is crucial to the maintenance of cancer cells in a proliferative state. DNA intercalation is a crucial part of topo II inhibition by DNA affinic anthraquinones. Potent cytotoxicity of anthraquinones, is related to their slow rate of dissociation from DNA, the kinetics of which favours long-term trapping of the topo-DNA complexes. Currently available DNA interacting agents at best promote a transient inhibition of topo II, since the topo-drug-DNA ternary complex is reversed by removal of the intracellular drug pool. Results: Alchemix cell cycle events: DNA content and Cyclin B1 expression were measured using flow cytometry and a p53 functional human osteosarcoma cell line (U2-OS) The results indicate: (ii) slow pan-cell cycle progression and mitotic commitment with a limited expression of G2 arrest, (iii) B1 cyclin tracking reveals that escape from Alchemix-induced cell cycle arrest in G2 is forcing some cells to enter polyploidy via an aberrant mitosis in keeping with topoisomerase II inhibition. Alchemix in vitro activity against the NCI human cell line panel including several drug resistant cancer cell lines had a mean IG50 = 49 nM. 11 of the 24 cell lines tested have an IG50 of <10 nM. Alchemix retains potent activity against chemotherapy resistant tumors including drug resistant ones. Conclusions: Alchemix possesses potent activity across a variety of different human tumors and significantly shows potent activity in cisplatin and anthracyline resistant human tumors Alchemix has pan-cell cycle effects. Multilevel targeting by Alchemix reduces the probability of evasion of cell cycle related pharmacodynamic responses. Results help explain the activity of Alchemix in both cisplatin and anthracycline resistant tumors in vitro and in vivo. [Table: see text]
Study of brain and whole blood PK/PD of bortezomib in rat models
Authors: Yu L. J. , Riordan B. , Hatsis P. , Brockman A. , Daniels S. , Stagliano N. , Finklestein S. , Ren J. , Milton M. , Miwa G. 
Published: March 2020

12036 Background: Bortezomib (Btz) is the first in class proteasome inhibitor and has been approved for treatment of multiple myeloma patients who have received at least 1 prior therapy. The potential for Btz to penetrate the CNS was examined in the rat under two conditions: intact blood brain barrier (BBB) and compromised BBB induced by middle cerebral artery occlusion (MCAO). Methods: Intact BBB: healthy rats received an iv bolus followed by a constant infusion of Btz to steady-state (SS). The blood and brain samples were collected for determination of concentration (Conc) of Btz (PK) and of 20S proteasome activity (PD). The brain samples were collected after a perfusion with saline. Inulin was included in the study in order to determine blood contamination in brain tissues. Compromised BBB: rats underwent MCAO surgery and 1 h later were administered Btz via an iv bolus of 0, 0.1, 0.2 or 0.35 mg/kg. The blood and brain samples were collected through 24 h postdose. Conc of Btz was determined by an LC/MS/MS method. The 20S proteasome activity was measured using an ex vivo assay. Results: 1) Intact BBB: at SS the mean blood Conc of Btz was 140 ng/mL, and proteasome activity in the blood was inhibited by ∼80% compared to the vehicle group (p < 0.0001). In contrast, the brain Conc of Btz was extremely low (∼3 ng/g) with the brain-to-blood ratio of ∼0.02. No difference was observed in brain proteasome activity between the vehicle and Btz-treated groups. 2)The MCAO rat: the PK/PD relationship in the blood was best described by a sigmoid Emax model with an EC50 of 110 ng/mL and gamma factor of 3.8. The model also suggests that there is no proteasome inhibition (PI) when the blood Conc is <40 ng/mL (no effective blood Conc, NOEBC). In the brain, the Cmax of Btz was 22.0 ng/g from the highest dose group, in contrast to the blood Cmax of 164 ng/mL. The increased exposure in the brain of a MCAO rat relative to a normal rat was anticipated as its BBB is impaired. However, the brain Concs were all below the NOEBC. No significant PI was observed in all brain tissues (P>0.1). Conclusion: Very poor brain penetration was observed for Btz in rats. Btz showed PI in whole blood but not in the brain either of normal or MCAO rats following administration of Btz. [Table: see text]
Combining tumor destruction by electrochemotherapy and innate immunity by CpG-ODN: Toward a new combination treatment for melanoma with skin metastases
Authors: Roux S. , Al Sakere B. , Bernat C. , Opolon P. , Garbay J. , Billard V. , Zitvogel L. , Carpentier A. , Mir L. , Robert C. 
Published: March 2020

12507 Background: Electrochemotherapy (ECT), consisting of electroporating cytotoxic agents (bleomycin or cisplatinum) in tumors, is effective in inducing destruction of cutaneous or subcutaneous tumors and can be used as a palliative treatment for patients with skin melanoma metastases. Our objective was to combine the antigen release induced by ECT with a potent and adapted stimulation of the innate immune system in order to induce a systemic anti-tumor response. Methods: The preclinical work was performed on murine models of skin tumors: fibrosarcoma (LPB) and melanoma (B16F10). We found that electrochemotherapy induced the recruitment of immune cells expressing CD11-c and Mac-1 in the first 48h after the treatment. By quantitative RT-PCR, we showed that this immune cell infiltrate was associated with an increase of TLR9 RNA expression. Therefore, we decided to combine ECT with intra-tumoral injection of TLR9 ligands: unmethylated CpG oligodeoxynucleotides (CpG-ODN). The distant and local antitumoral effect of this association (ECT + CpG-ODN) were tested in mice bearing a tumour on the two flanks (fibrosarcoma or melanoma). Animals were treated on the left flank only by a unique ECT course followed by intratumoral injection of CpG-ODN. Tumor growth rates were monitored on both treated (left) and non-treated (right) sides in order to assess direct and systemic antitumor effects of the association respectively. Experiments were also performed on nude mice, in order to investigate the role of lymphocytes in the systemic antitumor effect. Results: Compared to the separated treatments alone we found an increased local efficacy of the ECT-CpG-ODN, but, more importantly, we demonstrated a clear systemic effect of the combination on the controlateral tumors. In nude mice, no effect was observed in controlateral tumors suggesting a mechanism mediated by T lymphocytes. No significant financial relationships to disclose.