Pembrolizumab (mAb to PD-1) has been recently approved for the therapy of pretreated urothelial cancer. Despite the efficacy, it is often accompanied by unpredictable and sometime severe ...immune-related (ir) adverse events (AEs). Here, we report the clinical and immune–biological characterization of a patient with a metastatic bladder cancer who developed myositis signs (M) and a myasthenia-like syndrome (MLS) during treatment with pembrolizumab. The patient presented an autoimmunity-associated HLA haplotype (HLA-A*02/HLA-B*08/HLA-C*07/HLA-DRB1*03) and experienced an increase in activated CD8 T-cells along the treatment. The symptomatology regressed after pembrolizumab discontinuation and a pyridostigmine and steroids-based therapy. This is the first report of concurrent M and MLS appearance in cancer patients receiving pembrolizumab. More efforts are needed to define early the risk and the clinical meaning of irAEs in this setting.
Background: Capecitabine is considered the treatment of choice for anthracycline- and taxane-pretreated metastatic breast
cancer. Mitomycin C seems to improve the activity of capecitabine by ...up-regulation of thymidine phosphorylase. Patients and
Methods: Fifty-five women with metastatic breast cancer previously treated with anthracycline-taxane were treated with mitomycin
C 10 mg/m 2 on day 1 every six weeks and capecitabine 1000 mg/m 2 on days 2-15 every three weeks. Results: An overall response rate of 38% was found, consisting of 3 (5%) complete responses
(CR) and 18 (33%) partial responses (PR); 8 patients (14%) had a stable disease (SD) for more than 4 months. The combination
was well-tolerated, with the main toxicities being neutropenia, diarrhea and fatigue; other toxicities were of mild to moderate
intensity without impairment in the quality of life of the patients. Conclusion: Capecitabine is confirmed as the drug of
choice in the treatment of anthracycline- and taxane-pretreated metastatic breast cancer and its combination with mitomycin
appears to improve its efficacy.
Purpose
Erythropoiesis-stimulating agents (ESAs) are often used in treatment of patients with chemotherapy-induced anemia. Many studies have demonstrated an improved hemoglobin (Hb) response when ESA ...is combined with intravenous iron supplementation and a higher effectiveness of intravenous iron over traditional oral iron formulations. A new formulation of oral sucrosomial iron featuring an increased bioavailability compared to traditional oral formulations has recently become available and could provide a valid alternative to those by intravenous (IV) route. Our study evaluated the performance of sucrosomial iron versus intravenous iron in increasing hemoglobin in anemic cancer patients receiving chemotherapy and darbepoetin alfa, as well as safety, need of transfusion, and quality of life (QoL).
Materials and methods
The present study considered a cohort of 64 patients with chemotherapy-related anemia (Hb >8 g/dL <10 g/dL) and no absolute or functional iron deficiency, scheduled to receive chemotherapy and darbepoetin. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of IV ferric gluconate 125 mg weekly or oral sucrosomial iron 30 mg daily. The primary endpoint was to demonstrate the performance of oral sucrosomial iron in improving Hb response, compared to intravenous iron. The Hb response was defined as the Hb increase ≥2 g/dL from baseline or the attainment Hb ≥ 12 g/dL.
Results
There was no difference in the Hb response rate between the two treatment arms. Seventy one percent of patients treated with IV iron achieved an erythropoietic response, compared to 70% of patients treated with oral iron. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red blood cell transfusions and changes in QoL. Sucrosomial oral iron was better tolerated.
Conclusion
In cancer patients with chemotherapy-related anemia receiving darbepoetin alfa, sucrosomial oral iron provides similar increase in Hb levels and Hb response, with higher tolerability without the risks or side effects of IV iron.
Background: No standard chemotherapy has been defined for metastatic breast cancer patients pretreated with anthracyclines
and taxanes. In preclinical studies, mitomycin C (MMC) and capecitabine ...showed a synergistic effect by up-regulation of thymidine
phosphorylase, and both drugs were active against breast cancer with a lack of overlapping toxicity, making their combination
a well-tolerated regimen. Patients and Methods: A dose-finding study was carried out in order to determine the maximum tolerable
dose of MMC combined with fixed-dose capecitabine and to describe the dose-limiting toxicities. Results: Twenty-one patients
were enrolled, with metastatic breast cancer pretreated at least with anthracyclines and taxanes (3 at dose level I, 15 at
dose level II, 3 at dose level III). At dose level III (MMC 12 mg/m 2 and capecitabine 1000 mg/m 2 days 2-15) dose-limiting toxicities were recorded in 2 patients (G4 thrombocytopenia, neutropenic fever, G4 neutropenia);
dose level II (MMC 10 mg/m 2 and capecitabine 1000 mg/m 2 days 2-15) was extended for a better safety evaluation. No severe toxicity was noted at this dose level, and therefore this
dose was recommend for the phase II study. With regard to activity, 4 partial responses and 2 stable diseases (28%) were recorded.
Conclusion: Our data show that the combination is feasible, well tolerated and active in this set of patients.
Background
The BALLET study was an open‐label, multicenter, expanded access study designed to allow treatment with everolimus plus exemestane in postmenopausal women with hormone receptor‐positive ...metastatic breast cancer progressed following prior endocrine therapy. A post hoc analysis to evaluate if previous chemotherapy in the metastatic setting affects the safety profile of the combination regimen of everolimus and exemestane was conducted on the Italian subset, as it represented the major part of the patients enrolled (54%).
Patients and Methods
One thousand one hundred and fifty‐one Italian patients were included in the present post hoc analysis, which focused on two sets of patients: patients who never received chemotherapy in the metastatic setting (36.1%) and patients who received at least one chemotherapy treatment in the metastatic setting (63.9%).
Results
One thousand one hundred and sixteen patients (97.0%) prematurely discontinued the study drug, and the main reasons reported were disease progression (39.1%), local reimbursement of everolimus (31.1%), and adverse events (AEs) (16.1%). The median duration of study treatment exposure was 139.5 days for exemestane and 135.0 days for everolimus. At least one AE was experienced by 92.5% of patients. The incidence of everolimus‐related AEs was higher (83.9%) when compared with those that occurred with exemestane (29.1%), and the most commonly reported everolimus‐related AE was stomatitis (51.3%). However, no significant difference in terms of safety related to the combination occurred between patients without and with chemotherapy in the metastatic setting.
Conclusion
Real‐life data of the Italian patients BALLET‐related cohort were an adequate setting to state that previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane.
Implications for Practice
With the advent of new targeted agents for advanced or metastatic breast cancer, multiple lines of therapy may be possible, and components of the combined regimens can overlap from one line to another. Thus, it is important to assess even the potential of cumulative and additive toxic effects among the drugs. Previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The continuous monitoring of the safety signals of this drug combination from general clinical practice is important, in particular for stomatitis.
摘要
背景. BALLET研究是一项开放性、多中心、扩大供药研究, 患有激素受体阳性转移性乳腺癌且既往内分泌治疗后疾病进展的绝经后女性可在研究中接受依维莫司和依西美坦联合治疗。入组患者大部分为意大利人（54%）, 因此在意大利患者子集中进行了一项事后分析, 以评价既往在疾病转移后接受化疗是否会影响依维莫司和依西美坦联合治疗方案的安全性特征。
患者和方法. 本项事后分析纳入了1 151例意大利患者, 重点分析两组患者：从未接受过化疗的转移性乳腺癌患者（36.1%）和至少接受过一次化疗的转移性乳腺癌患者（63.9%）。
结果. 1 116例患者（97.0%）提前停用研究药物, 报告的主要原因为疾病进展（39.1%）、当地报销依维莫司（31.1%）和不良事件（AE；16.1%）。依西美坦和依维莫司的研究治疗中位持续时间分别为139.5天和135.0天。92.5%的患者至少发生1例AE。依维莫司（83.9%）相关AE的发生率高于依西美坦（29.1%）, 最常报告的依维莫司相关AE为口腔炎（51.3%）。然而, 接受和未接受化疗的转移性乳腺癌患者在联合治疗的相关安全性方面没有显著差异。
结论. BALLET研究中意大利患者队列的实际数据充分说明, 既往化疗不影响依维莫司和依西美坦联合治疗方案的安全性特征。
对临床实践的提示：晚期或转移性乳腺癌的新靶向药物问世后, 患者或许可以接受多线治疗, 而各线联合治疗方案中的药物可能相互重叠。因此, 评估药物毒性作用的潜在累积和叠加风险至关重要。既往化疗不影响依维莫司和依西美坦联合治疗方案的安全性特征。在一般临床实践中必须持续监测这一联合用药的安全性信号, 特别是口腔炎。
This study presents results of the BALLET study, which focused on the use of everolimus/exemestane combination in postmenopausal women with ER+ locally advanced or metastatic breast cancer after recurrence or progression after nonsteroidal aromatase inhibitor treatment. Real‐life data of the cohort are reported.
Bilingual volume published in cooperation with the Embassy of Italy in Poland and with the Italian Institute of Culture to celebrate the centenary of the Italian-Polish diplomatic relations ...(1919–2019).Texts by the renowned Italian and Polish authors (translated from Italian to Polish or vice versa) are divided into two parts: “Diplomacy, economy, history” and “Art, film, literature, theatre”. Such division allows to follow the Polish-Italian bonds in different fields, from translation and performance of the Italian tragedies on the Polish stages, to cooperation with the FIAT company. There is also reflection on the Polish-Italian relations in the difficult interwar period and during the Second World War. In this context one text has exceptional significance - that of Vincenzo Mario Palmieri, Italian anatomic pathologist and a member of the international commission that examined the Katyń massacre in 1943.The volume not only for the Italophiles but also for all those interested in the history of the 20th century and in the issues of the international relations.
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