bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pegylated liposomal doxorubicin in combination with gemcitabine in elderly women with locally advanced or metastatic breast cancer: Safety and activity results of our clinical experience
Authors: Adamo B. , Franchina T. , Denaro N. , Garipoli C. , Ferraro G. , Briguglio R. , Ricciardi G. R. , Gambadauro P. , Ferrandina G. , Adamo V. 
Published: August 2020

e12005 Background: Elderly breast cancer patients have an increased risk of toxicity from chemotherapy, especially from anthracycline-based regimens. Pegylated liposomal doxorubicin (PLD) has shown a better tolerability profile also in combination with gemcitabine (GEM), as evidenced in several phase II trials. The aim of this study is to retrospectively evaluate the safety and activity of this combination in chemo-naïve or pre-treated elderly patients with advanced breast cancer. Methods: From January 2006 to March 2008, 39 patients (pts) with age ≥ 65 received, at our institution, PLD 25 mg/m2 (day 1, q21) and GEM 800 mg/m2 (days 1 and 8, q21). Median age was 72 (range, 65–79). ECOG PS was 0/1/2 in 14/23/2 pts, respectively. 12 pts (31%) were chemo-naïve, 20 (51%) received prior adjuvant anthracycline-based regimens, and 7 (18%) received other chemotherapies. PLD-GEM combination was administered as first line in 35 pts (90%). Median left ventricular ejection fraction (LVEF) at baseline was 61% (range, 50%-75%). 28 patients (72%) had metastatic disease: 10 in liver, 6 in lung, 2 in skin, and 10 in multiple sites. Estrogen receptor was positive in 32 pts (82%); HER-2+ in 5 pts; 7 pts were triple negative. Results: A total of 206 cycles were administered with a mean number of cycles per patient of 5.2 (range, 3–12). Grade 3–4 neutropenia occurred in 4 (10%) and 3 patients (8%), respectively; grade 3 anemia in two pts (5%). Non-hematological toxicity was mild, with 5 cases (13%) of grade 3 mucositis, and 2 cases (5%) of grade 2 palmar-plantar erythrodysesthesia syndrome. No modifications in LVEF or toxic deaths were documented. We observed 1 CR (2.5%) and 11 PR (28.2%). Eighteen (44%) patients experienced SD for 16 weeks and an overall clinical benefit of 76.8%. Conclusions: The combination of PLD and GEM has a favorable tolerability and a safety profile with an evident clinical benefit and should represent an interesting treatment option in elderly women with advanced breast cancer. No significant financial relationships to disclose.
Late relapse in triple negative breast cancer
Authors: Tomasevic Z. , Radosevic-jelic L. , Tomasevic Z. M. , Jelic S. , Milovanovic Z. 
Published: August 2020

e12022 Background: Approximately 10%-15 % breast cancer (BC) are classified as triple negative. Although triple negative status carries grave prognosis, recent data suggests that it is mostly due to high relapse rate in first 2–3 years following initial diagnosis. Late relapses are less explored. The aim of this paper is to determine the percentage of triple negative BC among patients with late relapses, and to record relapse site in this subgroup of pts. Late relapse is determined as contra-lateral BC, loco-regional relapse, or any distant metastases at least 5 years after initial diagnosis of BC. Methods: Among 2,234 patients with various stages of BC registered during one year at the Institute for Oncology and Radiology of Serbia (March 2005-March 2006), 256 (11, 4%) had late relapse. Median time to relapse was 7 years (range 5–34 yrs). Median follow-up was 9 years. Results: IHC HER-2 status was retrospectively determined on 189 paraffin embedded primary BC specimen. HER-2 3 + is recorded in 17 specimen (8.9%); HER-2 2+/1+ in 86 (45.5%); and HER-2 0+ in 86 (45.5%) Among patients with HER-2 0+ only 10 also had ER score 0 and PGR score 0 (5.3%). Time to late relapse in this subgroup was 7.24 years (range 5–17 yrs). Relapses were resectable in 6 pts with local recurrence (4/10 pts) and contra-lateral BC (2/10). Three pts had bone metastases (3/10) and only 1 pt had pleural relapse (1/10). Median time to resectable relapse was 8.75 yrs (5–17). Median time to non-resectable relapse was 5.75 yrs (5–8 ). Conclusions: According to our results it seems that late relapse of triple negative BC is rare representing only 5.3% of late relapses. None of these pts had liver, lung, or brain metastases. Most relapses (6/10) could be resected, and therefore could potentially be cured. No significant financial relationships to disclose.
MGMT expression in low-grade gliomas
Authors: Lin Y. , Jiang T. , Li G. 
Published: August 2020

e13001 Background: To evaluate the expression of MGMT in low-grade gliomas, and explore the relationship between its expression and the histological type of the tumour and the corresponding MRI characteristics. Methods: We assessed 389 low-grade gliomas (182 astrocytomas, 145 oligoastrocytomas, 61 oligodendrocytomas) with immunohistochemistry staining. We also recorded the preoperational MRI criteria such as tumor volume on T2 image, enhancing volume, tumor location, and relationship with ventricles. Results: The expression of MGMT in astrocytomas, oligoastrocytomas, and oligocytomas were 1.67 ± 0.78, 1.41 ± 0.86,1.44 ± 0.78, respectively. Significant stronger expression of MGMT was observed in astrocytomas than oligoastrocytomas and oligodendrocytomas (t = 3.00, p = 0.03), but no significant difference was observed between the latter two (t = 0.28, p = 0.78). MGMT expression level was significantly correlated with the enhancing volume of the tumor (r = -0.605, p = 0.002), but did not correlate with the total tumor volume (p = 0.504). Conclusions: MGMT is more strongly expressed in tumors of solely astrocyte component, and its expression level is negatively correlated with the extent of blood-brain barrier disruption. This suggest that MGMT may contribute to the tumor resistance to radiotherapy and chemotherapy in low-grade gliomas. No significant financial relationships to disclose.
Phase Ib study of cediranib in combination with daily temozolomide and radiation in patients with newly diagnosed glioblastoma
Authors: Chi A. S. , Gerstner E. R. , Eichler A. F. , Chea H. K. , Drappatz J. , Wen P. Y. , Ivy S. P. , Loeffler J. S. , Sorensen A. G. , Jain R. K. , Batchelor T. T. 
Published: August 2020

e13010 Background: Pre-clinical evidence suggests antiangiogenic therapy combined with radiation therapy (RT) and chemotherapy may improve tumor control in patients with glioblastoma (GBM). We conducted a phase Ib study to evaluate the safety and maximum tolerated dose (MTD) of the combination of cediranib, a potent pan-VEGF receptor tyrosine kinase inhibitor, standard RT, and temozolomide (TMZ) in patients with newly diagnosed GBM who were not taking enzyme-inducing antiepileptic drugs (EIAED). Methods: After undergoing tumor biopsy or resection, six patients with pathologically confirmed GBM were treated with concurrent TMZ (75mg/m2/day), RT (60 Gy) and cediranib (dose level 1 = 20mg/day; dose level 2 = 30mg/day) followed by post-radiation TMZ (150–200 mg/m2 on days 1–5 of each 28 day cycle) and cediranib (45mg/day) for up to 6 monthly cycles. Cediranib was started concurrently with RT and TMZ 14–21 days after surgery. Results: Six patients were treated (cediranib 20mg = 3 patients; cediranib 30mg = 3 patients). No patients experienced a DLT, establishing the MTD for cediranib in combination with RT and TMZ as 30mg/day in this patient population. Expected toxicities of hypertension, fatigue, and palmar/plantar erythema were observed. During combined cediranib and TMZ therapy in the post-radiation setting, one patient discontinued cediranib because of toxicity (grade 3 transaminase elevation) and one patient required dose reduction to 15mg/day due to grade 3 proteinuria. No intratumoral or intracerebral hemorrhages were observed during the course of cediranib treatment. No cases of wound infection or wound dehiscence were observed. All patients are alive with a median follow-up of 156 days. Conclusions: Cediranib given in combination with standard RT and TMZ for newly diagnosed GBM patients not on EIAEDs is well tolerated and the MTD is 30mg/day. The phase II component of this trial is underway and will include correlative biomarker and MRI studies. [Table: see text]
Addition of continuous low dose temozolomide (T) to bevacizumab (Bev) plus irinotecan (Iri) after bevacizumab plus irinotecan failure in heavily pretreated glioblastoma multiforme (GBM)
Authors: Stankewitz S. , Dresemann G. 
Published: August 2020

e13015 Background: In several phase II studies in relapsed GBM, Bev plus Iri showed impressive objective response rates (>50%) with acceptable toxicity rate, duration of response, however, was moderate. Methods: From April 2007 to October 2008, 35 pretreated patients with confirmed GBM with progressive disease (PD) after Bev (4 mg/kg body weight i.v.) plus Iri (80 mg/m2 i.v.) were treated with additional continuous low dose T (20 mg per day p.o.) while Bev plus Iri were continued. ECOG performance status (PF) was 0 - 2 in all pts. MRI scan was required after 4 weeks and every 6 weeks afterwards. MacDonald criteria were used for evaluation of response. If MRI scans could not be performed, patients were considered to have PD. Treatment was given until PD or intolerable toxicity occurred. Results: All 35 patients were eligible for toxicity and efficacy, median follow up was 7 months (2 - 20), 25 patients were male, 10 female, median age was 51 years (29 - 80), 21 patients had primary GBM, 14 patients secondary GBM. All patients had prior irradiation (56 - 60 Gy) 2 patients had 5, 8 patients had 4, 15 patients had 3, and 10 patients 2 prior chemotherapeutic regimen. 1 patient developed grade 3 leucopenia, and 1 patients grade 3 thrombopenia; 3 patients asymptomatic intracerebral bleeds requiring treatment delay, 1 pat. grade 3 sepsis and 2 patients grade 3 fatigue. In 4/35 patients a partial response (PR) was achieved, in 14/35 patients a disease stabilization for at least 2 months, while 17/35 patients showed primary PD. Median duration of PR was 3.5 months (2–5), median duration of SD was 5 months (2–13), Median survival was 5 months (2–13). Data will be updated. Conclusions: The addition of continuous low dose T in combination with Bev plus Iri seems to have activity in GBM patients, after progression on Bev plus Iri treatment, and has an acceptable toxicity profile. Further investigation of the combination Bev plus Iri plus T in GBM patients is necessary. No significant financial relationships to disclose.
Seizures in patients with glioma treated with phenytoin and levetiracetam
Authors: Merrell R. T. , Lachance D. H. , Anderson S. K. 
Published: August 2020

e13020 Background: Seizures are common in patients with glioma. Phenytoin, traditionally used for these patients, can be associated with intolerable side effects and potentially alters the metabolism of chemotherapeutic agents. Levetiracetam has more favorable pharmacokinetics facilitating ease of use with fewer side effects and is nonenzyme inducing. We compare seizure outcomes and side effects in patients with glioma treated with phenytoin and levetiracetam monotherapy. Methods: Retrospective analysis of consecutive patients with glioma. Subjects had at least one clinical seizure and had to be followed for 6 months. Seizure outcomes and side effects were compared between cohorts treated with phenytoin or levetiracetam. Seizure outcomes were measured by time to second seizure and seizure frequency. Results: 76 patients (34 female) with pathologically proven glioma and seizures were identified, 25 treated with phenytoin and 51 with levetiracetam. 64% had grade 4 astrocytoma. There was no difference in seizure outcome between the phenytoin and levetiracetam groups when comparing time to second seizure (p = 0.584), second seizure rates (p = 0.462), and average seizures per month (p = 0.776). When adjusting for age, gender, type of seizure, type of glioma, and dosage using univariate and multivariate models there were no differences between the treatment groups and none of these covariates were statistically significant for explaining the second seizure rates between treatment groups (all p values >0.05). The incidence of side effects in the levetiracetam group was 5.9% versus 20% in the phenytoin group (p = 0.106). Additionally, 36.0% of the patients in the phenytoin group had dose adjustments not related to breakthrough seizures compared to only 9.8% in the levetiracetam group (p = 0.010). Conclusions: In this study, glioma patients treated with levetiracetam had similar seizure control as patients treated with phenytoin. Patients treated with levetiracetam experienced fewer side effects and required fewer non seizure related dose adjustments than patients treated with phenytoin. Levetiracetam is a safe, effective, and preferred alternative for seizure management in patients with glioma. No significant financial relationships to disclose.
A phase I study of sunitinib plus irinotecan in the treatment of patients with recurrent malignant glioma
Authors: Friedman H. S. , Vredenburgh J. J. , Desjardins A. , Janney D. E. , Peters K. B. , Friedman A. H. , Gururangan S. , Reardon D. A. 
Published: August 2020

e13024 Background: Malignant glioma (MG), an incurable primary CNS tumor, are highly angiogenic due to overexpression of VEGF/VEGFR. The current study was designed to determine the MTD and DLT of sunitinib (S), a once-daily, oral selective inhibitor of VEGFR when combined with irinotecan (I), a topoisomerase-1 inhibitor among recurrent MG patients. Methods: We employed a ‘3+3‘ dose escalation design to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S, administered once daily for the first 28 days of each 42 day cycle, with I, administered every 2 weeks. The initial S and I doses were 25 mg/day and 75 mg/m2. Key eligibility criteria included KPS ≥ 70%, adequate organ function and no concurrent CYP3A-inducing anti-epileptics. Pharmacokinetic studies for S are obtained during cycle 1 among 6 additional patients treated at the MTD. Results: Eleven patients (grade 4 MG, n = 6; grade 3 MG, n = 5) have enrolled. No DLTs were observed in cohort 1, but 2 patients experienced hematologic DLT (grade 3 thrombocytopenia, n = 2; grade 4 neutropenia, n = 1) in cohort 2. Therefore the MTD for this regimen is 25 mg of S plus 75 mg/m2 of I. Evidence of therapeutic benefit to date includes 8 patients (73%) with stable disease including 3 who continue on therapy. Conclusions: Combination of sunitinib plus irinotecan is well tolerated in recurrent MG patients at the defined MTD dose level. Accrual to the PK dose expansion cohort continues. No significant financial relationships to disclose.
Magnetic resonance imaging evaluation of radiation: Cranial radiation therapy-induced diffuse white matter injury
Authors: Mohran T. Z. , Omar M. M. , Hameed M. A. , Elnaggar M. S. 
Published: August 2020

e13033 Background: To study the value of MRI in detection and grading of diffuse white matter injury induced by cranial radiation therapy for brain tumors and to evaluate the influence of various risk factors for its development. Methods: This study included 60 patients who had primary brain tumors and received external beam conventionally fractionated radiotherapy. Twenty-three out of 60 patients received chemotherapy after radiotherapy. Post radiotherapy follow-up MRI examination was performed for all patients at 6 weeks, 3, 6, 9, 12 months, and at more than 1 year from completion of radiotherapy. MR imaging was performed with T2-weighted turbo spin echo, fast fluid-attenuated inversion- recovery (FLAIR), T1-weighted spin-echo, and T1-weighted post-contrast spin-echo sequences. Results: Twenty-one of 60 patients (35%) developed diffuse white matter injury at a mean of 15.3 + 7.6 months from the completion of radiotherapy (range, 5–36 months). Radiation-related diffuse white matter changes were characterized as diffuse high signal intensity in the periventricular deep white matter on T2WI and FLAIR sequences. The MRI grading system of these periventricular hyperintensity (PVH) were as follow: 39 patients (65%) had no WMI (grade 0), four had grade 1 changes, three patients had grade 2 changes, nine patients had grade 3, and five patients had grade 4. They were symmetrical in 13 of 21 patients (61.9%), and asymmetrical in eight out of 21 patients (38.1%). The prevalence of diffuse matter injury found to be significantly related to the volume of irradiation (p = 0.02), fraction size (p = 0.008), and concomitant use of chemotherapy (p > 0.02)Conclusions: Diffuse white matter injury is a known consequence of radiation therapy, and the capability of detecting and grading such damage is optimally provided by MRI. No significant financial relationships to disclose.
Liposomal doxorubicin and cisplatin as first-line chemotherapy in unresectable malignant pleural mesothelioma: A phase II study
Authors: Arrieta O. , Medina L. A. , Guzmán E. , Rios Trejo M. A. , Mendoza D. , Astorga Ramos A. , Martinez Barrera L. , Hernández Pedro N. , Arechaga Ocampo E. , De la Garza J. 
Published: August 2020

e13507 Background: Malignant pleural mesothelioma (MPM) is a poor prognosis neoplasm. Its worldwide incidence is rising but until recently chemotherapy has not been shown to be effective in its treatment. The combination of cisplatin and pemetrexed is the approved “standard” treatment in unresectable MPM. Liposomal doxorubicin (LD) consists of pegylated phospholipid- vesicles that encapsulate doxorubicin conferring minimal capture from the reticulo-endothelial system resulting in a greater serum half- life, an enhanced liposome deposition in the tumor and a lower degree of toxicity. We evaluated the combination of LD and Cisplatin (Cis) in chemonaive patients with unresectable MPM. Methods: From September 2006 to October 2008, consecutive patients with stage III / IV MPM were included to receive LD 40 mg/m2 and Cis 60 mg/m2 every 21 days for a maximum of 4 cycles. Imaging studies were performed prior and after 2 cycles to assess response. Gamma camera images (GCI) of Tc-99m-labeled LD were acquired to evaluate LD accumulation in measurable tumor tissue. Patients gave written informed consent. Results: Twenty seven patients were included, 81.5% were stage III and 18.5% were IV. According to EORTC prognostic factors, 33.3% and 66.7% had poor and good prognosis, respectively. Median age was 59.2 years (33–80). Median follow-up was of 5.2 ± 0.8 months. Median survival has not been reached. The 2-year overall survival was 52.5% ± 14.2. Median time to progression was 5.0 ± 1.1 months (CI 95%, 2.7–7.3). Overall response was 45.5%, stable disease 36.4% and progression of 18.2%. GCI showed good accumulation and retention (60%) of the labeled LD in tumor tissue at 4 h after the initial injection. There were no toxic deaths. Conclusions: Cis+LD is a highly active regimen in MPM with comparable results to the most active regimens so far reported. A phase III trial is warranted to confirm these findings. No significant financial relationships to disclose.
Trabectedin phase II clinical trials: Pooled analysis of safety in patients with solid tumors
Authors: Cioffi A. , LeCesne A. , Blay J. , Delaloge S. , Yovine A. , Maki R. , Nieto A. , Jiao J. J. , Demetri G. D. 
Published: August 2020

e13510 Background: Trabectedin is an originally marine-derived antineoplastic agent. Its unique antitumor properties, attributed to specific binding to the small groove of DNA, have been demonstrated activity against soft-tissue sarcoma (STS), ovarian, breast and prostate cancer. Trabectedin treatment has been authorized by EMEA for STS after failure of standard treatment and shows efficacy in relapsed ovarian cancer in a phase III study. This retrospective report on safety includes single-agent trabectedin phase II studies in patients (pts) with solid tumors. Methods: A total of 1,132 pts were treated with trabectedin in 19 international trials (Feb’99 - Apr’08). Three schedules were analyzed: 24-hour infusion every 3 weeks (wk) (570 pts), 3-h every 3 wk (258 pts), and 3-h for 3 out of 4 wk (304 pts). Safety analyses included pts who received at least part of 1 infusion. MedDRA and NCI-CTC v1.0/2.0 were used to code and grade treatment-emergent adverse events (AEs). Results: Median pt age was 54 years with ECOG 0–1 (>99%). Diagnosis included sarcoma (56%), ovary (26%) and breast (7%) cancer, for which 90% of pts had received chemotherapy, 37.5% radiotherapy, and 96.0% surgery. Trabectedin lasted for a median of 3 cy (9.4 wks) and 28% of pts received ≥ 6 cycles, with a median dose intensity of 0.4 (0.1–0.6) mg/m2/wk. The overall rate of discontinuations due to toxicity was 10.3%, similar between all three dose schedules. Most common trabectedin-related AEs (≥ 20% of pts) were nausea, fatigue and vomiting. Most common lab abnormalities were reversible myelosuppression, mainly neutropenia (37% grade3–4) though G-CSF was given to less than 10% of pts; and transient transaminase increases (grade3–4: ALT, 45%; AST, 30%). Of note, only 3.7% and 5.7% of pts had alopecia or mucositis/stomatitis, respectively. Fifteen drug-related deaths (1.3%) occurred. Conclusions: Single-agent trabectedin was reasonably well tolerated, with low rates of drug-related discontinuations and deaths. Sustained clinical benefit in the absence of relevant cumulative toxicities allows its administration to patients for prolonged periods of time. [Table: see text]
Administration of 24-hour intravenous infusions of trabectedin every 3 weeks in ambulatory patients with mesenchymal tumors via disposable elastomeric pumps
Authors: Schoeffski P. , Cerbone L. , Wolter P. , Stas M. , Dumez H. , Clement P. , Wildiers H. , Paridaens R. , van Oosterom A. T. 
Published: August 2020

e13530 Background: Patients (pts) with sarcoma whose disease progresses after standard chemotherapy have poor outcome. In this setting, DNA- transcription-interacting cytotoxic agent trabectedin (TRA) is efficacious and marketed in Europe. It is administered as 24-h i.v. infusion q3w with steroid co-medication. To overcome the inconvenience of hospitalization for drug delivery TRA is now given in Leuven via disposable elastomeric pumps, which facilitate ambulatory treatment and are compatible with the drug. Material and Methods: Heavily pre-treated pts with sarcoma were offered chemotherapy with TRA 1.5 mg/m2 as 24-h i.v. infusion via port catheter, either during hospitalization using electronic pumps or as outpatients using the Baxter LV10 disposable pump (drug dissolved in 267 ml NaCl 0.9%). Co-medication consisted of antiemetics and dexamethasone 2x4 mg days -1,1,2,3. Results: Between 09/07–12/08 28 pts were treated, and 21 (75%) elected outpatient therapy (9 F, 12 M, med. age 49 yrs, range 19–68). Common diagnoses included leiomyo- (5), lipo- (4), synovial (2) and myxofibrosarcomas. Pts had previous primary surgery (17), adjuvant RT (4) and surgery for relapse/metastasis (7). They had local relapse (2), distant metastasis (12) or both (7) when starting TRA, 19 had received previous chemotherapy with a med. number of 2 prior lines (range, 0–5). We administered 130 cycles of TRA in 21 pts, with a med. number of 3 cycles/patient (range, 1–24). Dose reductions were done in 60 cycles, mainly due to laborabory events. Best response (RECIST) was 3 confirmed PR, 1 PR pending confirmation, 6 SD, 11 PD. Grade 3/4 (CTC) AEs were limited to one case each of hemorrhage and lung embolism, other AEs were in line with published TRA experience. One port catheter contamination required replacement, one catheter tip thrombosis occurred and one extravasation due to needle dislocation was observed. Conclusions: Outpatient administration of TRA as 24-h infusion via port catheter using Baxter LV10 pumps is preferred by 3/4 pts, is feasible, safe, effective, cost-efficient and should be considered routine practice in this clinical setting. [Table: see text]