Development and validation of an HPLC-DAD method for the simultaneous identification and quantification of Topotecan, Irinotecan, Etoposide, Doxorubicin and Epirubicin

The knowledge of the chemical stability of drugs prepared and administered in hospital is of paramount importance for establishing the methods and times of their preparation, as well as for ensuring patient safety. The objective of this work was to develop and validate a single chromatographic method, according to the International Conference on Harmonization (ICH), United States Pharmacopeia (USP) and the European Pharmacopoeia (Ph. Eur.) guidelines, to allow the determination of the chemical stability of 5 chemotherapy drugs. The high performance liquid chromatography coupled with diode array detection (HPLC-DAD) method developed was found to be linear (all analytical curves showed R2 ≥ 0.999), sensitive, precise (RSDs < 3%) and accurate (recovery values ranging between 95% and 105%). The method was demonstrated to be robust to small deliberate variations such as column temperature, pH and composition of the mobile phase and also able to determine drug decomposition products. Therefore, the method described here is perfectly able to identify and quantify the chemotherapy drugs analysed

The Association of Four Natural Molecules-EGCG, Folic Acid, Vitamin B12, and HA-To Counteract HPV Cervical Lesions: A Case Report

Precancerous lesions of the uterine cervix, due to HPV infections, are still today a great medical challenge. This clinical case highlighted the effectiveness of epigallocatechin gallate (EGCG), vitamin B12, folic acid, and hyaluronic acid (HA) in counteracting HPV lesions in a 39-year-old patient with a long history of viral persistence, cervical lesions of various degree, and several unsuccessful surgical approaches. After eight weeks of treatment, both the histological and cytological analyses revealed only a chronic cervicitis without any malignant lesions or cellular dysplasia, thus reducing the urgency of an invasive surgery, a total hysterectomy

Pre-germinative requirements of maihuenia patagonica and maihueniopsis darwinii, endemic cacti from Patagonia

Cacti are characteristic plants in arid ecosystems, where they play an important ecological role. Many species are threatened because of habitat destruction and collection for commercial purposes. In South America, Argentina is one of the countries with the greatest cacti richness and endemisms. However, cacti have been scarcely studied, especially the southernmost species. Since the study of cacti’s reproductive biology would help to improve their conservation status, we studied basic physiological aspects of the germination of two endemic species of Argentina and Chile, Maihuenia patagonica (Phil.) Britton & Rose and Maihueniopsis darwinii (Hensl.) F. Ritter var. hickenii (Britton & Rose) R. Kiesling. Germination percentage (G), mean germination time (TMG) and time until germination (IG) of control seeds and seeds subjected to three pre-germinative treatments were evaluated. Treatments were cold moist stratification for 40 days, mechanical scarification with sand and sandpaper, and mechanical scarification with a scalpel. Laboratory assays were performed at 20/10 °C and 12 h light/12 h dark regime during 60 days. In M. patagonica germination in the stratification treatment did not differ from the control, but was higher in the scarification with scalpel. In M. darwinii var. hickenii germination only differed between the stratification and the scarification with scalpel. TMG and IG were higher in the stratification treatment than in the control for M. patagonica, whereas scarification treatments did not differ from the control. As for M. darwinii var. hickenii no differences were detected for TMG, but the IG was lower in the stratification than in the control. Probably both species presents some kind of dormancy, since germination percentages were low (M. patagonica between 8-27 % and M. darwinii var. hickenii between 17-26 %) but seeds presented high viability. Presence of physical dormancy is discarded because control seeds of both species germinated and the presence of non deep physiological dormancy is proposed. The latter was partially overcome by mechanical scarification in M. patagonica. These results are a new contribution to the study of cacti in South America and could help to develop in situ conservation strategies through the restoration of degraded areas.Fil: Masini, Ana Carla Ailín. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche. Laboratorio de Ecotono; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Rovere, Adriana. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche. Laboratorio de Ecotono; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Pirk, Gabriela Inés. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche. Laboratorio de Ecotono; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentin

Requerimientos pregerminativos de Maihuenia patagonica y Maihueniopsis darwinii, cactáceas endémicas de Patagonia

Cacti are characteristic plants in arid ecosystems, where they play an important ecological role. Many species are threatened because of habitat destruction and collection for commercial purposes. In South America, Argentina is one of the countries with the greatest cacti richness and endemisms. However, cacti have been scarcely studied, especially the southernmost species. Since the study of cacti’s reproductive biology would help to improve their conservation status, we studied basic physiological aspects of the germination of two endemic species of Argentina and Chile, Maihuenia patagonica (Phil.) Britton &amp; Rose and Maihueniopsis darwinii (Hensl.) F. Ritter var. hickenii (Britton &amp; Rose) R. Kiesling. Germination percentage (G), mean germination time (TMG) and time until germination (IG) of control seeds and seeds subjected to three pre-germinative treatments were evaluated. Treatments were cold moist stratification for 40 days, mechanical scarification with sand and sandpaper, and mechanical scarification with a scalpel. Laboratory assays were performed at 20/10 °C and 12 h light/12 h dark regime during 60 days. In M. patagonica germination in the stratification treatment did not differ from the control, but was higher in the scarification with scalpel. In M. darwinii var. hickenii germination only differed between the stratification and the scarification with scalpel. TMG and IG were higher in the stratification treatment than in the control for M. patagonica, whereas scarification treatments did not differ from the control. As for M. darwinii var. hickenii no differences were detected for TMG, but the IG was lower in the stratification than in the control. Probably both species presents some kind of dormancy, since germination percentages were low (M. patagonica between 8-27 % and M. darwinii var. hickenii between 17-26 %) but seeds presented high viability. Presence of physical dormancy is discarded because control seeds of both species germinated and the presence of non deep physiological dormancy is proposed. The latter was partially overcome by mechanical scarification in M. patagonica. These results are a new contribution to the study of cacti in South America and could help to develop in situ conservation strategies through the restoration of degraded areas.Las cactáceas son plantas características de ecosistemas áridos, en los cuales desarrollan un importante papel ecológico. Se encuentran amenazadas por la destrucción del hábitat y la extracción con fines comerciales. Argentina es uno de los países de Sudamérica con mayor riqueza y nivel de endemismo de cactáceas, sin embargo, su estudio es escaso, especialmente para las especies de distribución más austral. Dado que un mayor conocimiento sobre la biología reproductiva de los cactus ayudaría a mejorar su conservación, se estudiaron aspectos fisiológicos básicos sobre la germinación de dos especies endémicas de Argentina y Chile, Maihuenia patagonica (Phil.) Britton &amp; Rose y Maihueniopsis darwinii (Hensl.) F. Ritter var. hickenii (Britton &amp; Rose) R. Kiesling. Se evaluó el porcentaje de germinación (G), el tiempo medio de germinación (TMG) y los días transcurridos hasta el inicio de la germinación (IG) de un control y de tres tratamientos pre-germinativos: estratificación húmeda fría, escarificación mecánica con lija y arena, y escarificación mecánica con bisturí. El ensayo se extendió por 60 días, en cámara de germinación a 20/10 °C, 12 h luz/12 h oscuridad. Para M. patagonica la germinación no difirió entre la estratificación y el control, pero fue mayor al control en la escarificación con bisturí. Para M. darwinii var. hickenii la germinación sólo difirió entre la estratificación y la escarificación con bisturí. El TMG y el IG fueron mayores para la estratificación que para el control en M. patagonica, mientras que los tratamientos de escarificación no difirieron del control. En el caso de M. darwinii var. hickenii no se observaron diferencias en el TMG, pero el IG fue menor en la estratificación que en el control. Es posible que ambas especies presenten algún tipo de dormancia, ya que los porcentajes de germinación fueron bajos (M. patagonica de 8-27 % y M. darwinii var. hickenii de 17-26 %), pero las semillas presentaron elevada viabilidad. Se descarta la existencia de dormancia física debido a que hubo germinación en el control de ambas especies y se propone la existencia de dormancia fisiológica leve, la cual habría sido superada parcialmente por la escarificación mecánica con bisturí del tegumento en M. patagonica. Los resultados obtenidos constituyen un nuevo aporte al estudio de las cactáceas de Sudamérica, que puede ser utilizado para el desarrollo de medidas de conservación in situ mediante la restauración de hábitats naturales degradados

Explaining the aggressiveness of breast cancer in sub-Saharan African patients

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Multicentric survey on dose reduction/interruption of cancer drug therapy in 12.472 patients: Indicators of suspected adverse reactions

Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012.Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events.Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012. Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events

Use of the ONCO-TreC electronic diary compared with a standard paper diary to improve adherence to oral cancer therapy in patients with solid and haematological tumours: protocol for a randomised controlled trial

Introduction ONCO-TreC platform consists of a mobile application delivered to patients as electronic diary and a web-based dashboard managed by healthcare professionals. We aim to compare the effectiveness of ONCO-TreC electronic diary with a standard paper diary, in improving adherence to oral cancer therapy in patients with solid and haematological tumours. Methods and analysis This is an open label, superiority, randomised controlled trial conducted in two Italian oncology units. Patients will be randomised with a 1:1 ratio to electronic or paper diary. For both groups a counsellor will be responsible for drug and diary delivery. The evaluation period will end after six cycles of therapy. The primary aim is to compare the proportion of non-adherent patients in the two arms. Adherence will be measured through pill count; anyone who takes less than 90% of the total prescribed drug dose will be considered non-adherent. Assuming a percentage of non-adherent patients to oral therapy of 40% in arm B, and a 60% reduction in this percentage in arm A, a sample of 124 patients will provide 80% power to identify an absolute difference greater than 24 percentage points using a bilateral Fisher’s exact test with a significance level of 0.05. Considering a dropout rate of 10%, approximately 136 patients will have to be enrolled. The primary analysis will be performed on the intention-to-treat population. Secondary aims are to describe the reasons for non-adherence, the level of satisfaction of patients and healthcare professionals with the paper and electronic diary, and the impact of non-adherence in terms of healthcare costs. Ethics and dissemination Ethical approval was obtained from Romagna Ethics Committee (CEROM), study ID 2108, prot. n. IRST 100.28 of 10/04/2020. Informed consent will be obtained from all study participants. Findings will be disseminated through peer-reviewed journals, conferences and event presentations

A real-world retrospective, observational study of first-line pembrolizumab plus chemotherapy for metastatic non-squamous non-small cell lung cancer with PD-L1 tumor proportion score < 50% (PEMBROREAL)

IntroductionThe phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known EGFR and ALK driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 &lt;50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program.MethodsPEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan–Meier method), response to therapy, and tolerability.ResultsUntil February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5–9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate.ConclusionThe results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily