bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prelimenary results of a phase I/II of a combination of cetuximab and taxane for triple negative breast cancer patients
Authors: Nechushtan H. , Steinberg H. , Peretz T. 
Published: August 2020

e12018 Background: The triple negative subtype of breast cancer is currently only treated with chemotherapeutic agents. It has been demonstrated that over 50% of this kind of tumors express EGFR (HER-1). Cetuximab is a humanized antiEGFR IgG1 antibody. In colon cancer there are also high percentage of EGFR expression and addition of Cetuximab to chemotherapy results in renewed sensitivity to treatments. We therefore hypothesized that in a similar manner addition of Cetuximab to taxanes which are among the most potent anti breast cancer drugs will result in increased effectiveness in this subset of breast cancer patients. Methods: From January 2007 to January 2009, we treated 12 breast cancer patients with either paclitaxel 80 mg/m2, (10 patients) or docetaxel (30 mg mg/m2) (2 patients), with cetuximab weekly. Patients had a pathology sample of breast cancer with triple negative components, metastatic disease and up to two prior chemotherapy lines in the metastatic settings. Results: Patient characteristics (median): age 60 (31–69) years, prior taxane therapy 9/12 pts. Toxicity: Dermatologic grade 2 9/12 grade 3 3/12, nail disease grade 2 10/12 evaluable patients. One patient developed severe swallowing difficulties after 19 month of therapy which may or may not be linked to the treatment. Response is evaluable for 11/12 patients. Response which includes clinical response, tumor marker decrease, and a metastasis size decrease was noted in 9/11 patients. Including tumor marker normalization and nearly a roentgoenolgic CR in a young patient previously treated with several chemeotherapietic lines. Three patients developed brain metastasis during treatments. Molecular pathology is now performed. We continue accrual. Conclusions: Administration of taxane-cetuximab weekly therapy for triple negative breast cancer patients is possible. Toxicity is the cumulated expected toxicity of each of the agents — special care should be taken for nail disease which occurred in most of the patients. Some impressive clinical responses were obtained even in taxane pretreated patients. [Table: see text]
Capecitabine (X) in the routine treatment of advanced breast cancer (BC): Results from a large (n = 870) noninterventional study
Authors: Schoenegg W. 
Published: August 2020

e12021 Background: This observational study evaluated patient (pt) characteristics, treatment schedule and setting, efficacy and tolerability of X in routine clinical practice in Germany. Methods: Pts with advanced BC pretreated with or ineligible for anthracycline-containing therapy received X. As there was no specific protocol for X administration, data on dose, treatment duration, treatment delays/interruptions, and concomitant anticancer therapy were collected as well as efficacy data. Pts were followed until disease progression or completion of 12 cycles (with long-term follow-up in pts who were progression-free after 12 cycles). Results: Between 2002 and 2007, 870 pts were recruited from 135 centers, of whom 846 were eligible. Most pts (62%) were aged 50–69 years and 64% had received prior taxane therapy. X was given as monotherapy in 64% (median starting dose 1070 mg/m2 bid) and combination chemotherapy in 36% (median starting dose 987 mg/m2 bid), typically with vinorelbine or docetaxel. Generally, pts receiving X alone were slightly older and were more likely to have hormone receptor-positive disease than those receiving combination therapy. 35% of pts received X as first-line therapy. Pts received a median of 7 cycles; 26% received ≥12 cycles. Overall response rate (RR) was 41% (95% CI: 38–45) and median progression-free survival (PFS) was 7.5 months (95% CI: 7.1–8.3). RR was higher with combination therapy (49%) than monotherapy (37%), but PFS was similar in the two subgroups. Good performance status at baseline was a significant predictor of efficacy. The most common non-hematologic adverse event was hand-foot syndrome (all grades: 54%; grade 3: 7%), leading to premature treatment discontinuation in 6%. Myelosuppression and alopecia were substantially less common when X was administered as monotherapy than as combination chemotherapy. Conclusions: X, either alone or in combination, is a feasible and effective treatment for advanced BC. Our findings in real-life clinical practice compare favorably with results from interventional studies, perhaps reflecting the longer treatment duration possible at a more tolerable dose. No significant financial relationships to disclose.
Peritoneal disease in breast cancer: A specific entity with an extremely poor prognosis
Authors: Tuthill M. H. , Pell R. , Giuliani R. , Adrian L. , Lewis J. S. , Leonard R. , Coombes C. , Stebbing J. 
Published: August 2020

e12023 Background: We are observing increasing numbers of patients with advanced breast cancer and peritoneal metastases. There are few published data regarding the prognosis, clinical characteristics, and management of such individuals. Methods: The electronic imaging database at Charing Cross Hospital was searched for the terms ’breast,’ ’cancer or tumor,’ ’peritoneal,’ and ’ascites’ from 2000–2008. Those with confirmed peritoneal disease from breast cancer, as described on ultrasound or staging CT reports with a clinico-pathologic confirmed diagnosis, were included in the study. Results: A total of 1,628 scans were screened and initially 168 patients were identified. A subsequent total of 44 individuals (2.7% of the metastatic cohort) were included in this study, as having breast cancer with peritoneal secondaries. Of these, the majority (77%) had invasive ductal carcinomas (IDC). While the median survival from the diagnosis of metastatic breast cancer measured 20.5 months (range 0.1 -125 months), the median survival of patients with peritoneal disease was 1.56 months (range 0.2 - 27 months). Conclusions: Our data shows that the median survival of patients with peritoneal breast cancer metastasis is surprisingly poor, with only a minority surviving more than six months. A specific association with invasive lobular carcinoma (ILC) was not observed. The dismal outcome of these individuals despite further active therapy merits their inclusion into trials of new treatments. No significant financial relationships to disclose.
Hormonal changes with anastrozole treatment in breast cancer
Authors: Ali S. , Ali M. F. , Mundia M. , Mundia A. G. 
Published: August 2020

e12026 Background: Aromatase inhibitors are a class of drugs that inhibit tumor growth in hormone receptor positive breast cancer, in postmenopausal women. They inhibit the conversion of androgens to estrogens. Both clinical benefit and side effects are believed to be due to alterations in blood hormonal levels. Methods: Clinical charts of postmenopausal women with estrogen receptor positive breast cancer, receiving anastrozole 1 mg daily, were reviewed to determine the clinical side effects and blood hormonal changes during treatments, at a community oncology practice. Hormonal levels measured were serum testosterone, serum estrogens and prolactin levels. Results: There were 31 postmenopausal women age 52–73 (median 62) years, receiving anastrozole 1 mg daily. Duration of treatment was 8 to 42 (median 24) months. Clinical side effects noted were joint pains in 4 patients; mild to moderate hot flashes in 4; temporary nausea lasting for 1 week in 3; and vaginal dryness in 2 patients. Serum estrogen levels dropped by 20% in 10 patients from baseline but remained within normal range (14–103 pg/mL), there were no changes in serum testosterone (range 14–76 ng/mL) or prolactin (2.8–29 ng/ml) levels. 2 out of 4 patients with joint pains had testosterone levels in upper range, and remained unchanged during treatments. Conclusions: Anastrozole 1 mg daily is well tolerated in clinical practice, in terms of side effects and does not cause significant blood hormonal changes. No significant financial relationships to disclose.
Treatability of patients with metastatic breast cancer after treatment by ixabepilone in first-line
Authors: Thivat E. , Dalenc F. , Durando X. , Gladieff L. , Mouret-Reynier M. , Kwiatkowski F. , Deslandres M. , Chollet P. , Roché H. 
Published: August 2020

e12030 Background: Ixabepilone (BMS-247550), an epothilone B analog, was an active drug in metastatic breast cancer (MBC) patients who were anthracycline pretreated. The main toxicity was mild to moderate neuropathy which was primarily sensory and mostly reversible. This study was performed to evaluate retrospectively the treatability of patients after discontinuation of ixabepilone given as first metastatic line in 2 institutions. Methods: From February 2001 to December 2002, 50 patients (median age 54 years) were enrolled in a phase II clinical trial evaluating ixabepilone as first line chemotherapy (CT) in MBC. Fifteen patients were treated by 50 mg/m2 (as a 1-hour infusion subsequently amended as a 3-hour infusion), and 34 received ixabepilone at 40 mg/m2 IV infusion during 3 hours every 3 weeks in response to the early safety findings. Neurotoxicity occurred in 38 patients (76%) leading to treatment discontinuation in 19 patients (38%). The description of subsequent treatments after ixabepilone was realized to detect eventual cross resistance and subsequent neurotoxicity. Results: Patients received a median number of 3 subsequent CT (range, 0–11) whatever the ixabepilone dosage. The median duration of subsequent CT lines after ixabepilone was of 3.6 months (range, 0–15.6 months). Patients who developed neurotoxicity received a median of 3 subsequents CT (range, 0–9), and those who did not, received a median of 1.5 subsequent lines. Forty-four patients received a second metastatic CT with different regimens stratified according the main cytotoxic agents, which were capecitabine in 54.5% of patients, taxane in 18.2%, and vinorelbine in 15.9%. At third line of metastatic CT (n = 37), taxane based regimen, capecitabine based regimen, and vinorelbine based regimen were administered respectively in 45.9%, 16.2%, and 13.5%. Median survival from first administration of ixabepilone was of 25.3 months (range, 0.2–89.2 months). After ixabepilone treatment, best response rate of subsequent CT was of 18.4%, and neurotoxicity was observed in 42.1%. Conclusions: In spite of neurotoxicity development with ixabepilone used as first metastatic line, the administration of subsequent lines of CT for treated MBC, especially with taxane based regimen, was normally possible. No significant financial relationships to disclose.
Impact of MGMT methylation status on 1p/19q intact anaplastic gliomas
Authors: Franceschi E. , Tosoni A. , Ermani M. , Spagnolli F. , La Torre L. , Galzio R. J. , Pozzati E. , Talacchi A. , Benevento F. , Brandes A. A. 
Published: August 2020

e13003 Background: Chromosomes 1p/19q codeletion has been recognized as a prognostic and predictive factor in patients (pts) with grade 3 gliomas. Non-codeleted (intact) anaplastic oligodendroglioma showed a survival comparable to that usually observed in pts with anaplastic astrocytomas; MGMT methylation status, moreover, has been found to be a prognostic factor in glioblastoma and anaplastic gliomas (AG). Methods: A retrospective analysis was made using a database of 253 AG pts followed prospectively between January 1998 and August 2008. We evaluated only pts who met the following inclusion criteria: age ≥ 18 years; PS 0–2; histological diagnosis of AG with 1p/19q intact, as determined by FISH analysis; treatment with postoperative radiotherapy (RT) and chemotherapy (CT); MGMT status determined using methylation specific PCR. The study aim was to evaluate the role of MGMT methylation status in 1p/19q codeleted AG pts. The log-rank test was used to evaluate the significance of the prognostic variables. Results: 67 pts (m/f: 35/32, median age: 41.3 years, range: 18–70 years) were enrolled. Histology was anaplastic oligodendroglioma in 17 pts, anaplastic oligoastrocytoma in 20 pts, and anaplastic astrocytoma in 30 pts; all these pts were 1p19q intact and received surgery, RT, and CT. MGMT status, assessable in 58 pts (86.6%), was methylated in 33 pts (56.9%), and unmethylated in 25 pts (43.1%). Median progression-free survival (PFS) was 32.3 months (95%CI: 9.9–54.7). No enhancement at time of diagnosis (p = 0.003), gross total resection (p = 0.03), age (p = 0.001), and MGMT methylation (p = 0.05) were significantly correlated with better PFS. Median survival was 65.2 months (95% CI: 45–85.3). Only age (p = 0.001) and KPS (p = 0.02) correlated with a better survival. Conclusions: MGMT methylation status may provide adjunctive prognostic information in pts with 1p/19q intact AG, indicating a prolonged PFS in pts harboring MGMT promoter methylation. No significant financial relationships to disclose.
Phase 1 study of LY317615 (enzastaurin) and temozolomide in patients with gliomas - EORTC trial 26054
Authors: Rampling R. , Sanson M. , Taal W. , Lai C. , Stoffregen C. , Munoz M. , Gorlia T. , Govaerts A. , Lacombe D. , Van den Bent M. 
Published: August 2020

e13005 Background: Enzastaurin (Enz) is a small selective inhibitor of protein kinase C (PKC). Synergy with temozolomide (TMZ) has been demonstrated in vitro. This phase I trial investigated optimal dosing and toxicity when Enz was combined with a standard TMZ regimen. Methods: Patients (pts) with recurrent high-grade glioma or newly diagnosed disease not amenable to radiotherapy (RT) and WHO PS 0–1 were eligible. Pts on EIAEDs were excluded. Two dose levels (DL) of Enz were explored. DL1: Loading dose 500 mg followed by 250 mg daily. DL2: Loading dose 1,125 mg followed by 500 mg daily. TMZ was given at 150 mg/m2 d1-d5 every 28 days in cycle 1, escalating to 200 mg/m2 in subsequent cycles. Dose-limiting toxicity (DLT) was defined by CTCAE 3.0 criteria in the first two cycles as (1) any non haematological toxicity grade 3/4 (2) ANC < 500/mm3 (3) thrombocytopenia grade 3/4 (4) any toxicity reducing drug dose intensity to <80%. Results: 15 pts were included, three at DL1, 12 at DL2. 13 pts had received prior RT, seven prior chemotherapy, and two were newly diagnosed. Median number of cycles was four (range 2–8).Treatment is ongoing in five pts. TMZ dose was escalated in all pts with no DLT. Modest and reversible thrombocytopenia was the most frequent toxicity, occurring in seven pts (3 @ Gd 1, 3 @ Gd2, 1 @ Gd 3) and led to TMZ dose reduction in two pts and treatment delays in four pts (multiple in 2). One pt discontinued after three cycles due to persistent thrombocytopenia. Five pts developed neutropenia not requiring dose modification. Two pts developed hyperbilirubinemia. Six SAE's (3 at each DL) were recorded, and one death (DL2). None was considered treatment related. Two pts showed a partial response, six pts stable disease. Conclusions: Enz can be safely combined with standard TMZ regimen. Results of the just completed phase I part with Enz 250 mg twice daily dosing will also be presented at the meeting. [Table: see text]
Five-year survival data in newly diagnosed glioblastoma treated with radiotherapy along with concurrent and adjuvant temozolomide
Authors: Wadasadawala T. , Jalali R. , Munshi A. , Gupta T. , Kalyani N. , Menon H. , Sarin R. , Goel A. 
Published: August 2020

e13009 Background: We report 5-year survival data in patients with newly diagnosed glioblastoma treated with radiotherapy along with concurrent and adjuvant temozolomide (TMZ). Methods: Between March 2001 to April 2008, 81 patients with newly diagnosed histopathologically proven glioblastoma underwent surgery followed by external radiotherapy to a total dose of 60 Gy in 30 fractions over 6 weeks. Concurrent oral TMZ (75 mg/m2) was given daily with RT followed by adjuvant TMZ for 5 days every 28 days for six cycles (150 mg/m2 for the first cycle and 200 mg/m2 for rest of the cycles). Patients were monitored clinicoradiologically as per standard practice. Results: Patients aged between 11–73 years with a median age of 49 years (60 males, 21 females). Forty per cent of patients underwent a gross total resection of tumour, 44% had partial resection, and 16% an open or stereotactic biopsy only. 79% of the patients had a post-operative Karnofsky Performance Score (KPS) of >80. All six adjuvant cycles were completed in 68%. The 2-, 3-, 4-, and 5-year survival was 34%, 24%, 11%, and 11%, respectively (95% CI 14.03–21.96). The median overall and progression-free survival was 18 (2–92 months) and 16 months (2–72 months), respectively. On multivariate analysis, completion of all six cycles of adjuvant TMZ was associated with significantly better survival (p = 0.000). Neurological performance score (NPS) of 2–3 (p = 0.06) and Recursive Partitioning Analysis class V (p = 0.093) showed a trend towards poorer outcome. Treatment was generally well tolerated with only 2.5% of patients developing grade 3 anemia, leucopoenia, and neutropenia. Grade 3 or 4 thrombocytopenia was seen in 5% patients. Conclusions: Concurrent radiotherapy and TMZ followed by adjuvant TMZ results in encouraging survival even at a long follow-up. No significant financial relationships to disclose.
Angiogenesis and expression of estrogen and progesterone receptors as predictive factors of recurrence in meningiomas: A long-term prospective study
Authors: Saavedra D. , Guevara-Salazar P. , Escobar-Arriaga E. , Martinez-Rumayor A. , Rembao D. , Calderon A. , Sotelo J. , Arrieta O. 
Published: August 2020

e13013 Background: Meningioma is a bening tumor, with a high rate of recurrence after surgery (80%); the most important relapse predictive factor is the extent of surgical resection; other potentially predictive factors have been studied with poor results. Angiogenesis has an important role in growth and spread of neoplasic cells; previous studies have shown a high incidence of cyclin E (CE), estrogen, and progesterone receptors (ER, PR) in meningiomas. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF), vascular density index (VDI), cell proliferation index (CPI), CE, ER, and PR tissue expression in meningioma recurrence of patients submitted to surgical resection. Methods: From January 1995 to December 2000, we enrolled 42 patients with histopathological diagnosis of meningioma and treated only with surgical resection. Tumor VDI, CPI, CE, ER, and PR tissue expression were evaluated by immunohistochemistry in patients with or without recurrence. CPF, VDI, CPI, and expression of CE, ER, and PR were associated with recurrence. Results: Complete surgical resection was achieved in 32.5% of patients. Minimal follow-up was 6 years. Recurrence of meningioma was found in 17 patients (40%). Mean time of recurrence was 32 + 8 months. Tissue expression was positive for CE, ER, and PR in 90.9%, 27.6%, and in 64% of patients, respectively. VDI was >8 (40X in 10 fields) in 52.6% of patients and CPI was >600 (40X in 10 fields) in 54.2% of patients. Significant recurrence-associated factors were extent of resection (RR = 2.4, 95% CI 1.7–2.9, p = 0.03) and VDI >8 (RR = 1.7, 95% CI 1.003–2.9, p = 0.001). CPI, CE, ER, and PR expressions were not statistically significant (p = 0.83, p = 0.16, p = 0.46, and p = 0.74, respectively). Conclusions: Patients with partially resected meningioma and high VDI have an increased recurrence risk and could benefit of additional therapeutic measures. No significant financial relationships to disclose.
Pilot study of topotecan and thalidomide in patients with recurrent malignant gliomas
Authors: Khosla P. , Monga V. , Taaca A. 
Published: August 2020

e13019 Background: Adults with glioblastoma multiforme (GBM) treated with radiation and chemotherapy have median survival of less than 12 months from diagnosis. Topotecan is a topoisomerase-1 inhibitor with activity in brain tumors and very little nonhematologic toxicity. Continuous infusion has been shown to have decreased hematologic toxicity. Thalidomide has antiangiogenic and immnunomodulatory effects. The combination would offer a multitargeted approach with no overlapping toxicity. Methods: Single-center prospective phase II study of 10 patients (median age 50, range 38–70) with high-grade recurrent glioma treated at Rush University Medical Center between 2002 and 2006 following IRB approval. All patients had failed at least one standard therapy and received a combination of the two drugs: topotecan by continuous infusion for 21 days, every 28 days at 0.4 mg/m2/day through a permanent in-dwelling catheter and thalidomide with starting oral dose of 100 mg/day, escalated by 100 mg/day per week to maximum of 400 mg/day by day 28. Dose reductions were made for grade 3 and 4 hematologic or nonhematologic toxicities. All patients received coumadin 1 mg/day DVT/PE prophylaxis. Assessment of response was done every 8 weeks by MRI and MRS. Results: Median number of cycles of study drugs = 3; median time to progression = 4 months; median survival = 12 months; DVT/PE = 40% of patients with low-dose coumadin prophylaxis. Conclusions: The combination of topotecan and thalidomide is feasible and shows moderate activity. The study is limited by small size and thromboembolic complications likely related to thalidomide in 40% of patients. Low-dose coumadin prophylaxis was not adequate in preventing thrombosis. [Table: see text] No significant financial relationships to disclose.
Clinical significance of prophylactic intrathecal chemotherapy in the treatment of glioblastoma multiforme
Authors: Iuchi T. , Hatano K. , Sakaida T. , Hirono S. 
Published: August 2020

e13022 Backgrounds: We previously have reported that hypo-fractionated high-dose irradiation (HdI; 68Gy/8F) showed excellent local control but no effect on prevention of cerebrospinal fluid dissemination (CSFd), resulted in limited efficacy on patients’ survival in glioblastoma (GBM). The aim of present analysis is to evaluate the clinical significance of prophylactic intrathecal administration of thiotepa (iT) in the treatment of GBM patients. Methods: Histologically confirmed GBMs without CSFd at diagnosis were enrolled. Patients were classified into four groups owing to the post-surgical treatment strategy as follows: Group A patients (n = 65) were treated by conventional radiotherapy (cRT; 60Gy/30F) alone; Group B patients (n = 17) were by cRT concurrent witn iT; Group C patients (n = 28) were by HdI alone; Group D patients (n = 30) were by HdI concurrent with iT. In Group B and D, Ommaya reservoir was placed into the lateral ventricle and 10mg of thiotepa was administrated weekly after surgery for five times. The local progression-free survival (PFS), CSFd-free survival (CFS), and overall survival (OS) were compared in these four groups. Results: Group C and D patients showed significantly longer PFS than Group A and B (p < 0.0001), suggesting the clinical significance of HdI for local control of this tumor. On the other hand, CFS in Group B and D was significantly longer than that in Group A and C (p = 0.049), demonstrating the effect of iT for prevention of CSFd. However, significant improvement of OS on the conventional treatment (Group A, median OS: 12.3 months) was observed only in Group D (median OS: 30.2 months, p = 0.002) and not in Group B or C (24 months, p = 0.135, and 14.9 months, p = 0.481 respectively). Conclusions: These data indicated that both of local control and prevention of CSFd were required for better survival of patients with GBM, and iT concurrent with HdI may be one of the treatments that fill these requirements. No significant financial relationships to disclose.