A new rapid desensitization protocol for chemotherapy agents

Background: Desensitization has been used for some decades to treat patients with the allergenic drug when an alternative drug with similar effi cacy and safety is not available. We present the results from a series of oncology patients desensitized at our hospital during the last 2 years. Objective: To assess the effi cacy of a new desensitization protocol in patients allergic to chemotherapy drugs. Methods: We performed an observational retrospective study of 11 women (6 breast cancer and 5 ovarian cancer) who underwent our desensitization protocol. Four patients had immediate reactions to carboplatin, 3 to docetaxel, 3 to paclitaxel, and 1 to both docetaxel and paclitaxel. Premedication was administered in all cases. A 5-step protocol based on 5 different dilutions of the drugs was used. Results: We performed 39 desensitization procedures: 14 to carboplatin, 3 to oxaliplatin, 16 to docetaxel, and 6 to paclitaxel. Eight patients tolerated the full dose in 36 procedures. One patient suffered an anaphylactic reaction to carboplatin that reverted with treatment. One patient had dyspnea after a paclitaxel cycle. One patient experienced dyspnea due to chronic pulmonary thromboembolism related to her disease. Conclusion: Desensitization is a useful procedure in patients who are allergic to their chemotherapy agents

Efficacy and safety of trabectedin in metastatic uterine leiomyosarcoma: A retrospective multicenter study of the Spanish ovarian cancer research group (GEICO)

Objective: We assessed trabectedin in patients with advanced uterine leiomyosarcoma (uLMS) in real-life clinical practice given according to the marketing authorization. Methods: Thirty-six women from 11 tertiary hospitals across Spain who received trabectedin after anthracyclinecontaining regimen/s were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Results: Median PFS and overall survival (OS) since starting trabectedin treatment were 5.4 (95%CI: 3.5–7.3) and 18.5 months (95%CI: 11.5–25.6), respectively. Median OS was significantly higher (P = 0.028) in patients receiving trabectedin in ≤ 2nd line (25.3 months) than in ≥ 3rd (15.1 months) and with ECOG performance status ≤ 1 at trabectedin start (19.8 months) than ECOG 2–3 (6.0 months, P = 0.013). When calculating OS since diagnosis, patients had longer OS with localized disease at diagnosis (87.4 months) vs. locally advanced (30.0 months) or metastatic (44.0 months, P = 0.041); and patients who received adjuvant therapy (87.4 months) compared with those who did not (30.0 months, P = 0.003), especially when receiving radiochemotherapy (106.7 months, P = 0.027). One patient (2.8%) had a complete response (CR) and nine patients (25.0%) achieved a partial response (PR) for an objective response rate of 27.8% with median response duration of 11 months (range: 4–93). Eighteen patients (50.0%) had disease stabilization for a disease control rate (DCR) of 77.8%. More patients receiving trabectedin in 1st-line of advanced disease achieved CR (16.7%) and PR (50.0%) than those in ≥ 2nd line/s (0.0% and 20.0%), whereas the DCR was similar across treatment lines. Reversible neutropenia was the most common grade 3/4 laboratory abnormality (19.4%). Conclusions: Trabectedin confers clinical benefit in patients with recurrent/metastatic uLMS, given after failure to an anthracycline-based regimen being comparable to those reported in clinical trials and with a manageable safety profile

Tratamiento hormonal del cáncer de mama

Hormonal therapy has been the first systemic treatment against breast cancer. Up to now Tamoxifen and ovarian supression/ablation were the best optionts we had to treat early breast cancer as advancer disease. The advent of aromatase inhibitors, new SERMS and antistrogen Fulvestrant have supoused a great advance in the treatment of this disease and at the same time have complicated the election of the optimal drug for each patient. This article tries to review the aviable treatment options insiting on its indications

Factor von Willebrand como intermediario entre la hemostasia y la angiogénesis de origen tumoral

Cancer patients often show an imbalance condition between coagulation system and fibrinolysis which causes a prothrombotic state. Different molecular factors like von Willebrand factor (vWf), presenting higher plasmatic rates in these patients, play an important role in this situation. During active angiogenesis taking place in tumor growth, the vascular endothelial growth factor (VEGF) and the fibroblast growth factor (FGF-2) contribute to the proliferation and differentiation of endothelial tissue, the main vWf producer, promoting increased rates of vWf in the serum of neoplastic patients. Recently vWf's contribution to tumor cells and platelet adhesion has been described. In this process, the discovery of platelet, endothelial and tumor cell membrane integrins and their implication in cellular adhesion has represented a major step in demonstrating how blood clotting and platelet aggregation are mediated by tumor cell and platelet linkage. Migration properties acquired by tumor cells as a result of this binding have been also pointed out. Clinical trials show higher rates of plasmatic vWf in cancer patients the more advanced clinical and radiological stage they present (metastasic versus localized). Moreover, higher pre-surgical serum vWf rates in patients can be used to predict poorer survival after resection surgery. vWf high molecular weight multimers have been also related to a cleavage protease deficiency in the serum of the oncologic population. The promising results of antiaggregation/anticoagulation therapies in these patients permit us to envisage new therapeutic target

Current management and future perspectives in metastatic HER2-Positive breast cancer

Objective: Metastatic HER2-positive breast cancer remains a significant clinical challenge with a poor prognosis. The introduction of anti-HER2 therapies has significantly improved survival in early and advanced stages. However, patients with metastatic HER2-positive breast cancer eventually experience progression due to de novo or acquired resistance. This review article comprehensively analyzes the current management of metastatic HER2-positive breast cancer, addressing the complexities in determining the optimal HER2-targeted therapy sequence. Data Sources: Discussion of selected peer-reviewed articles and expert opinion. Conclusions: We explore the actual standard of care and the emerging therapeutic options that hold promise for further improving patient care and survival in this aggressive breast cancer subtype. This article highlights vital toxicities linked to anti-HER2 therapies, emphasizing their recognition across treatments as interstitial lung disease, diarrhea, or left ventricular dysfunction. Implications for Nursing Practices: Oncology nurses have a key role to play in detecting potential adverse effects of anti-HER2 therapies. The development of new drugs, as antibody drug conjugates, with a distinct toxicity profile makes it necessary for us to be updated on the management of these new toxicities

Tratamiento hormonal del cáncer de mama

Hormonal therapy has been the first systemic treatment against breast cancer. Up to now Tamoxifen and ovarian supression/ablation were the best optionts we had to treat early breast cancer as advancer disease. The advent of aromatase inhibitors, new SERMS and antistrogen Fulvestrant have supoused a great advance in the treatment of this disease and at the same time have complicated the election of the optimal drug for each patient. This article tries to review the aviable treatment options insiting on its indications

Combination of pegylated liposomal doxorubicin plus gemcitabine in heavily pretreated metastatic breast cancer patients: Long-term results from a single institution experience

The combination of Pegylated Liposomal Doxorubicin (PLD) plus Gemcitabine (GEM) has been previously investigated in the treatment of metastatic breast cancer (MBC). PLD is a doxorubicin formulation with prolonged circulation time and better tissue distribution. GEM is a nucleoside analog with nonoverlapping toxicity compared to PLD. The aim of our study was to assess efficacy, toxicity, and long-term outcome of this combination. Patients with heavily treated MBC were retrospectively analyzed. Chemotherapy consisted of PLD 25 mg/m2 and GEM 800 mg/m2 day 1, on a three-week schedule. Cardiac function was evaluated baseline and during treatment. Radiological response was graded according to RECIST criteria v1.1. Toxicity was scored according to CTCAE v4.0. Progression-free survival (PFS) and overall survival (OS) were evaluated. From 2001 to 2014, 122 pts were included. Median age was 55 (range: 28-84). Median previous treatment schedules in the metastatic scenario were 3 (range: 1-15). Most patients received prior anthracyclines (85%). Median number of metastatic sites was 2 (range: 1-7). Median number of cycles delivered was 5 (range: 1-36). Overall response rate was 31% (5% complete responses; 26% partial responses). Stable and progressive diseases were observed in 32% and 26% of patients. Grade ≥3 neutropenia was observed in 29 patients (24%). Grade ≥3 hand-foot syndrome was detected in 17 patients (14%), mostly since cycle 3 (88%). Median cumulative PLD dose was 125 mg/m2. At a median follow-up of 101 months, median PFS and OS were 7 and 22 months, respectively. PLD-GEM combination achieves remarkable long-term outcomes with an acceptable toxicity profile in patients with MBC

A new rapid desensitization protocol for chemotherapy agents

Background: Desensitization has been used for some decades to treat patients with the allergenic drug when an alternative drug with similar effi cacy and safety is not available. We present the results from a series of oncology patients desensitized at our hospital during the last 2 years. Objective: To assess the effi cacy of a new desensitization protocol in patients allergic to chemotherapy drugs. Methods: We performed an observational retrospective study of 11 women (6 breast cancer and 5 ovarian cancer) who underwent our desensitization protocol. Four patients had immediate reactions to carboplatin, 3 to docetaxel, 3 to paclitaxel, and 1 to both docetaxel and paclitaxel. Premedication was administered in all cases. A 5-step protocol based on 5 different dilutions of the drugs was used. Results: We performed 39 desensitization procedures: 14 to carboplatin, 3 to oxaliplatin, 16 to docetaxel, and 6 to paclitaxel. Eight patients tolerated the full dose in 36 procedures. One patient suffered an anaphylactic reaction to carboplatin that reverted with treatment. One patient had dyspnea after a paclitaxel cycle. One patient experienced dyspnea due to chronic pulmonary thromboembolism related to her disease. Conclusion: Desensitization is a useful procedure in patients who are allergic to their chemotherapy agents

Efficacy and safety of trabectedin in metastatic uterine leiomyosarcoma: A retrospective multicenter study of the Spanish ovarian cancer research group (GEICO)

Objective: We assessed trabectedin in patients with advanced uterine leiomyosarcoma (uLMS) in real-life clinical practice given according to the marketing authorization. Methods: Thirty-six women from 11 tertiary hospitals across Spain who received trabectedin after anthracyclinecontaining regimen/s were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Results: Median PFS and overall survival (OS) since starting trabectedin treatment were 5.4 (95%CI: 3.5–7.3) and 18.5 months (95%CI: 11.5–25.6), respectively. Median OS was significantly higher (P = 0.028) in patients receiving trabectedin in ≤ 2nd line (25.3 months) than in ≥ 3rd (15.1 months) and with ECOG performance status ≤ 1 at trabectedin start (19.8 months) than ECOG 2–3 (6.0 months, P = 0.013). When calculating OS since diagnosis, patients had longer OS with localized disease at diagnosis (87.4 months) vs. locally advanced (30.0 months) or metastatic (44.0 months, P = 0.041); and patients who received adjuvant therapy (87.4 months) compared with those who did not (30.0 months, P = 0.003), especially when receiving radiochemotherapy (106.7 months, P = 0.027). One patient (2.8%) had a complete response (CR) and nine patients (25.0%) achieved a partial response (PR) for an objective response rate of 27.8% with median response duration of 11 months (range: 4–93). Eighteen patients (50.0%) had disease stabilization for a disease control rate (DCR) of 77.8%. More patients receiving trabectedin in 1st-line of advanced disease achieved CR (16.7%) and PR (50.0%) than those in ≥ 2nd line/s (0.0% and 20.0%), whereas the DCR was similar across treatment lines. Reversible neutropenia was the most common grade 3/4 laboratory abnormality (19.4%). Conclusions: Trabectedin confers clinical benefit in patients with recurrent/metastatic uLMS, given after failure to an anthracycline-based regimen being comparable to those reported in clinical trials and with a manageable safety profile

Assessing the impact of the addition of dendritic cell vaccination to neoadjuvant chemotherapy in breast cancer patients: A model-based characterization approach

Aims: Immunotherapy is a rising alternative to traditional treatment in breast cancer (BC) patients in order to transform cold into hot immune enriched tumours and improve responses and outcome. A computational modelling approach was applied to quantify modulation effects of immunotherapy and chemotherapy response on tumour shrinkage and progression-free survival (PFS) in naïve BC patients. Methods: Eighty-three Her2-negative BC patients were recruited for neoadjuvant chemotherapy with or without immunotherapy based on dendritic cell vaccination. Sequential tumour size measurements were modelled using nonlinear mixed effects modelling and linked to PFS. Data from another set of patients (n = 111) were used to validate the model. Results: Tumour size profiles over time were linked to biomarker dynamics and PFS. The immunotherapy effect was related to tumour shrinkage (P < .05), with the shrinkage 17% (95% confidence interval: 2-23%) being higher in vaccinated patients, confirmed by the finding that pathological complete response rates in the breast were higher in the vaccinated compared to the control group (25.6% vs 13.6%; P = .04). The whole tumour shrinkage time profile was the major prognostic factor associated to PFS (P < .05), and therefore, immunotherapy influences indirectly on PFS, showing a trend in decreasing the probability of progression with increased vaccine effects. Tumour subtype was also associated with PFS (P < .05), showing that luminal A BC patients have better prognosis. Conclusions: Dendritic cell-based immunotherapy is effective in decreasing tumour size. The semi-mechanistic validated model presented allows the quantification of the immunotherapy treatment effects on tumour shrinkage and establishes the relationship between the dynamics of tumour size and PFS