Aim: High-grade glioblastoma multiforme (GBM) has a poor median overall survival (OS). The standard treatment after surgery is temozolomide and radiotherapy (RTH). Patients with unmethylated methylguanine-methyltransferase promoter (MGMT) have no or little benefit from temozolomide and are eligible for alternative therapies. Gemcitabine is a good radiosensitizer. We aimed to evaluate the combination of gemcitabine with RTH in newly diagnosed GBM. Methods: The study was a prospective phase II study. Eligible patients were required to have histologically proven anaplastic astrocytoma or GBM. Patients underwent biopsies or subtotal resection. The treatment consisted of fixed-dose rate gemcitabine 175 mg/m 2 weekly followed after 24 h by standard cranial RTH for 6 weeks. Tumor response was evaluated by Macdonald criteria. In case of progression, patients received temozolomide (200 mg/m 2 /5 days every 28 days). Results: Thirty patients with a median age of 52 years (30-69), 73%/27% male/female, the Eastern Cooperative Oncology Group performance status 1 (range 0-2) were enrolled. Five patients had a partial-response (17%) and 13 stable-disease (43%). Median time to progression was 7.88 months (95% CI 6.1-9.69) and OS was 11.77 months (95% CI 9.97-13.56). The treatment was well tolerated with grade-3 neutropenia in 3, grade-3 anemia in 2 and impaired liver enzymes in 1 patient. Conclusion: Gemcitabine followed by radiotherapy is active and promising regimen in newly diagnosed GBM. Gemcitabine uptake is easy, with a long local retention of active metabolites, precluding systemic side effects of radiosensitization. In a phase III study this treatment should be evaluated in patients with unmethylated MGMT promoter who will not benefit from temozolomide.
Background: Unverified penicillin allergy has been linked to adverse patient events and increased healthcare expenditure owing to the usage of broad-spectrum, expensive antibiotics. Penicillin allergy test is the gold standard to diagnose penicillin allergy; and in this study, we present data from Qatar which have not been published before. Methods: Patients with a history of penicillin allergy who underwent penicillin allergy testing between January 2015 and December 2020 at the Allergy Division of the Hamad General Hospital were retrospectively reviewed from the division registry. Benzylpenicilloyl-polylysine (PPL) and minor determinant mixture (MDM) kit DAP-penicillin (0.04 mg +0.5 mg)/vial) (penicillin G, amoxicillin (20 mg/vial), and lately clavulanic acid (20 mg/vial) (DAP, Diater, Madrid, Spain) were used for skin and intradermal testing according to published guidelines. Patients with negative skin tests were administered direct oral challenge with amoxicillin/clavulanate (500/125 mg) and observed for 2 hours. Results: Of the 189 charts reviewed, 183 patients had a complete data set for analysis. Patients were predominantly women (n = 132, 72%) with an average age of 42 years. Of these patients, 149 (81.4%) had a history of an immediate allergic reaction to penicillin, 10 had a history of delayed reactions, and 24 had other or undefined reactions. A total of 39 (21.3%) patients were diagnosed with penicillin allergy (30 patients with positive skin test results and 9 using a direct oral challenge). Of the 30 patients with positive skin testing, 5 reacted to PPL, 8 to MDM, 13 to amoxicillin, and 4 to clavulanic acid. Conclusion: Previous studies indicate that 90% patients with a history of penicillin allergy were able to tolerate the drug (10% were truly allergic). Our data showed that 21% were truly allergic to penicillin. This high positive rate can be attributed to the high pretest probability based on the detailed history obtained before the test, which led to the exclusion of patients with symptoms incompatible with penicillin allergy from the test.
Background and Aim: Management of metastatic breast cancer (MBC) remains a great challenge for oncologists. The aim of our study was to evaluate the efficacy and toxicity of capecitabine combined with vinorelbine as a second line treatment in MBC. Materials and Methods: Twenty-three patients with MBC received oral capecitabine (1000 mg/m 2 /day) for 14 days plus vinorelbine (oral 60 mg/m 2 days 1, 8 and 15 or intravenous 25 mg/m 2 days 1and 8 according to patients' preference and drug availability). Results: The median age of patients was 52 years and 61% of them were ER-ve / PR-ve and 91% were HER2-ve. Eighty-three percent of patients failed treatment with anthracyclines and 48% with taxanes. The majority (83%) received the oral formulation of vinorelbine and the median number of cycles per patient was 3. The overall response rate was 56.5%; however, none of the patients achieved complete remission. The median progression free survival for the whole group of patients was 4.2 month. Grade 3-4 hematological toxicities were more likely to occur with the oral vinorelbine regimen and there were no treatment-related deaths. Conclusions: Metronomic capecitabine and vinorelbine combination seems to be tolerable and effective as a second line chemotherapy in MBC. A higher dose of capecitabine in combination with vinorelbine, may improve survival and increase the response rate.
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.
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