Assessment of hair loss and skin changes during treatment in Asian breast cancer patients: A prospective cohort study.

With the increasing number of young breast cancer (BC) patients worldwide, concerns about hair loss and skin change persist among BC survivors. This study aimed to evaluate the hair loss and skin changes in Asian BC patients and to compare them according to the treatment regimens. This study enrolled 322 patients scheduled to undergo BC surgery. Hair loss and skin changes were assessed at the following two time points: one day before surgery and 6 months after surgery. Patients who had received systemic anticancer treatment before surgery were assigned to the neoadjuvant treatment group, while patients who were scheduled to receive systemic anticancer treatment were assigned to the adjuvant treatment group. In the adjuvant treatment group, patients with taxane-based chemotherapy had significantly higher odds of increased hair loss, a higher melanin index, and an increased volume of wrinkles (p < 0.0001, p = 0.0110, and p = 0.0371, respectively). In the neoadjuvant treatment group, hair loss was reversed in most patients at 6 months after surgery. Clinicians should inform BC patients about the potential for hair loss and skin changes and provide supportive care to mitigate the effects on the patients' quality of life.

Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane + anthracycline versus taxane-based chemotherapy regimens: A SEER-medicare study.

BACKGROUND: Triple-negative breast cancer (TNBC) is more aggressive as compared to other subtypes of breast cancer with characteristic metastatic patterns and a poor prognosis. The standard of care for early-stage TNBC is historically anthracycline and taxane-based chemotherapy (ATAX). Despite the effectiveness of this regimen, anthracyclines carry a small but important risk of cardiotoxicity, which is specifically a concern in the older population. This study evaluates major adverse cardiovascular events (MACE) in older women with TNBC treated with ATAX compared to taxane-based chemotherapy (TAX). METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified women aged 66 and older with TNBC diagnosed between 2010 and 2015 (N = 2215). We compared patient and clinical characteristics according to adjuvant chemotherapy regimen (chemotherapy versus no chemotherapy and ATAX versus TAX). Logistic regression was performed to estimate the odds ratios (OR) and 95% confidence intervals (CIs), Kaplan-Meier survival curves were generated to estimate three-year overall survival (OS) and cancer specific survival (CSS). Cox proportional hazards models were used to analyze OS and CSS while controlling for patient and tumor characteristics. MACE was defined as acute myocardial infarction, heart failure, potentially fatal arrhythmia, and cerebral vascular incidence. Few patients experienced a cardiac death and therefore this was excluded in the analysis. RESULTS: Of the 2215 patients in our cohort, most patients (n = 1334; 60.26%) received TAX compared to ATAX (n = 881; 39.78%). Patients who received ATAX were not statistically significantly more likely than those who received TAX to experience acute myocardial infarction, cerebral vascular accident (CVA), or potentially fatal arrhythmia when controlling for traditional risk factors. Among patients who experienced MACE, there was no difference in OS or CSS in patients who received TAX vs ATAX. Patients who received ATAX were less likely to develop heart failure than those who received TAX (OR 0.63, 95% CI [0.45-0.88], p < 0.01). Patients who developed MACE and who were > 76 years old had worse OS compared to those who experienced MACE and were age 66-75 years old (HR 1.67, 95% CI [1.07-2.62], p = 0.02). CONCLUSION: Among older women with TNBC, receipt of adjuvant chemotherapy with ATAX was not associated with increased risk of major adverse cardiac events. For those who experienced a cardiac event, there was no difference in survival amongst those who received TAX vs ATAX. Other factors including additional chemotherapy toxicities should be investigated as a potential etiology for the inferior OS previously observed with ATAX vs TAX in older women with node negative or 1-3 positive lymph nodes.

Palonosetrón: prevención de náuseas y vómitos en adultos, inducidos por quimioterapia de moderada y altamente emetógena / Palonosetrón: prevention of nausea and vomiting in adults, induced by moderate and highly emetogenic chemotherapy

CONTEXTO CLÍNICO: Las náuseas y los vómitos inducidos por la quimioterapia son graves y preocupantes. existen varios tratamientos antieméticos eficaces y bien tolerados por el paciente, no obstante, las náuseas y los vómitos inducidos por la quimioterapia sigue siendo un efecto adverso importante del tratamiento. La emesis se puede medir objetivamente mediante observación directa e independiente. Las náuseas, que a menudo acompañan a la emesis, son una sensación subjetiva que requiere el autoinforme del paciente para cuantificarla. Se han definido tres tipos distintos de náuseas y los vómitos inducidos por la quimioterapia: aguda, tardía y anticipatoria. Reconocer las diferencias entre estos tipos de náuseas y los vómitos inducidos por la quimioterapia tiene implicaciones importantes tanto para la prevención como para el tratamiento. Emesis aguda: la emesis aguda se define como la que ocurre durante las primeras 24 horas después de la quimioterapia. En ausencia de una profilaxis eficaz, lo más habitual es que comience entre una y dos horas después de la quimioterapia y, por lo general, alcanza su punto máximo en las primeras cuatro a seis horas. INFORMACIÓN FARMACOLÓGICA: Palonosetrón es un antagonista del receptor 5-HT 3 con una fuerte afinidad de unión por este receptor y poca o ninguna afinidad por otros receptores. ESTRATEGIAS DE BÚSQUEDA DE INFORMACIÓN: Se realizó una búsqueda en las principales bases de datos bibliográficas Pubmed, términos utilizados náuseas, vómitos, inducidos, quimioterapia, prevención, emesis, altamente emetógena, moderadamente emetógena. Se filtra la búsqueda a Estudios Clínicos fase III, controlados randomizados, Revisiones Sistemáticas, Meta-análisis, Guías de Práctica Clínica, además se limitó la búsqueda estudios en humanos. También se realiza búsqueda manual en otras bases de datos bibliográficas (Cochrane, NIH, TRIP DATABASE), en buscadores genéricos de internet, agencias de evaluación de tecnologías sanitarias y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas, metaanálisis, estudios clínicos aleatorizados y controlados, guías de práctica clínica, evaluaciones de tecnología sanitaria, evaluaciones económicas y políticas de cobertura de otros sistemas de salud. CONCLUSIONES: El agente de segunda generación palonosetrón tiene una afinidad de 30 a 100 veces mayor por el receptor 5-HT3 y una vida media significativamente más larga (40 horas) en comparación con los antagonistas del receptor 5-HT3 de primera generación (29).Las náuseas y los vómitos inducidos por la quimioterapia (CINV) son un efecto adverso importante del tratamiento. El factor más importante que determina la probabilidad de que se desarrolle una emesis aguda o retardada es la emetogenicidad intrínseca de un agente quimioterapéutico en particular. Como agente único, palonosetrón es más eficaz que ondansetrón o dolasetrón para prevenir la emesis debida a agentes quimioterapéuticos de emetogenicidad variable (30). Esto quedó ilustrado por un ensayo multicéntrico en 592 pacientes, la mayoría de los cuales recibieron doxorrubicina y ciclofosfamida para el cáncer de mama; una minoría recibió regímenes de quimioterapia basados en cisplatino y carboplatino. Los sujetos fueron asignados aleatoriamente a una dosis única IV de palonosetrón en uno de dos niveles de dosis (0,25 o 0,75 mg IV) o dolasetrón (100 mg). Más pacientes tratados con palonosetrón (0,25 mg) tuvieron un control completo de la emesis aguda (63 frente a 53 por ciento) y tardía (54 frente a 39 por ciento) en comparación con dolasetrón. La dosis de 0,75 mg no fue significativamente superior en comparación con la de 0,25 mg. Un ensayo diseñado de manera similar también demostró la superioridad del palonosetrón en comparación con el ondansetrón. Cuando se usa en combinación con glucocorticoides, palonosetrón proporciona un control superior de la emesis retardada en comparación con los antagonistas del receptor 5-HT3 de primera generación combinados con glucocorticoides. Las directrices antieméticas actualizadas de la Red Nacional Integral del Cáncer (NCCN) recomiendan palonosetrón como el antagonista 5-HT3 preferido para pacientes que reciben quimioterapia moderadamente emetógena. Por el contrario, las directrices actualizadas de la Asociación Multinacional de Atención de Apoyo en Cáncer (MASCC)/Sociedad Europea de Oncología Médica (ESMO) y la Sociedad Americana de Oncología Clínica (ASCO) no especifican un antagonista 5-HT3 preferido para pacientes que reciben tratamiento emetógeno moderado. Los antagonistas del receptor 5-HT3 son generalmente seguros, con un perfil de efectos secundarios favorable (predominantemente dolor de cabeza leve, malestar general y estreñimiento.

Cost-effectiveness of adjuvant chemotherapy for high-risk stage II and stage III colon cancer in South Africa.

BACKGROUND: Colon cancer incidence is rising in low- and middle-income countries (LMICs), where resource limitations and cost often dictate treatment decisions. In this study, we evaluate the cost-effectiveness of adjuvant chemotherapy for high-risk stage II and stage III colon cancer treatment in South Africa (ZA) and illustrate how such analyses can inform cancer treatment recommendations in a LMIC. METHODS: We created a decision-analytic Markov model to compare lifetime costs and outcomes for patients with high-risk stage II and stage III colon cancer treated with three adjuvant chemotherapy regimens in a public hospital in ZA: capecitabine and oxaliplatin (CAPOX) for 3 and 6 months, and capecitabine for 6 months, compared to no adjuvant treatment. The primary outcome was the incremental cost-effectiveness ratio (ICER) in international dollars (I$) per disability-adjusted life-year (DALY) averted, at a willingness-to-pay (WTP) threshold equal to the 2021 ZA gross domestic product per capita (I$13,764/DALY averted). RESULTS: CAPOX for 3 months was cost-effective for both patients with high-risk stage II and patients with stage III colon cancer (ICER = I$250/DALY averted and I$1042/DALY averted, respectively), compared to no adjuvant chemotherapy. In subgroup analyses of patients by tumor stage and number of positive lymph nodes, for patients with high-risk stage II colon cancer and T4 tumors, and patients with stage III colon cancer with T4 or N2 disease. CAPOX for 6 months was cost-effective and the optimal strategy. The optimal strategy in other settings will vary by local WTP thresholds. Decision analytic tools can be used to identify cost-effective cancer treatment strategies in resource-constrained settings. CONCLUSION: Colon cancer incidence is increasing in low- and middle-income countries, including South Africa, where resource constraints can impact treatment decisions. This cost-effectiveness study evaluates three systemic adjuvant chemotherapy options, compared to surgery alone, for patients in South African public hospitals after surgical resection for high-risk stage II and stage III colon cancer. Doublet adjuvant chemotherapy (capecitabine and oxaliplatin) for 3 months is the cost-effective strategy and should be recommended in South Africa.

New and Persistent Sedative-Hypnotic Use After Adjuvant Chemotherapy for Breast Cancer.

BACKGROUND: Sedative-hypnotic medications are used to treat chemotherapy-related nausea, anxiety, and insomnia. However, prolonged sedative-hypnotic use can lead to dependence, misuse, and increased health-care use. We aimed to estimate the rates at which patients who receive adjuvant chemotherapy for breast cancer become new persistent users of sedative-hypnotic medications, specifically benzodiazepines and nonbenzodiazepine sedative-hypnotics (Z-drugs). METHODS: Using the MarketScan health-care claims database, we identified sedative-hypnotic-naïve patients who received adjuvant chemotherapy for breast cancer. Patients who filled 1 and more prescriptions during chemotherapy and 2 and more prescriptions up to 1 year after chemotherapy were classified as new persistent users. Univariate and multivariable logistic regression analyses were used to estimate odds of new persistent use and associated characteristics. RESULTS: We identified 22 039 benzodiazepine-naïve patients and 23 816 Z-drug-naïve patients who received adjuvant chemotherapy from 2008 to 2017. Among benzodiazepine-naïve patients, 6159 (27.9%) filled 1 and more benzodiazepine prescriptions during chemotherapy, and 963 of those (15.6%) went on to become new persistent users. Among Z-drug-naïve patients, 1769 (7.4%) filled 1 and more prescriptions during chemotherapy, and 483 (27.3%) became new persistent users. In both groups, shorter durations of chemotherapy and receipt of opioid prescriptions were associated with new persistent use. Medicaid insurance was associated with new persistent benzodiazepine use (odds ratio = 1.88, 95% confidence interval = 1.43 to 2.47) compared with commercial or Medicare insurance. CONCLUSIONS: Patients who receive sedative-hypnotic medications during adjuvant chemotherapy for breast cancer are at risk of becoming new persistent users of these medications after chemotherapy. Providers should ensure appropriate sedative-hypnotic use through tapering dosages and encouraging nonpharmacologic strategies when appropriate.

Impact of the 21-Gene Recurrence Score Assay on Treatment Decisions and Cost in Patients with Node-Positive Breast Cancer: A Multicenter Study in Quebec.

BACKGROUND: The 21-gene Breast Recurrence Score (RS) assay, "the assay", has led to a paradigm shift for patients with hormone receptor-positive, node-negative early breast cancer and is emerging as an important tool to assist physician-patient decisions in foregoing chemotherapy in node-positive patients. We wanted to better understand the impact of the RS assay in node-positive patients upon physician treatment decisions and treatment cost in Quebec, Canada. PATIENTS AND METHODS: We conducted a multicenter, prospective observational trial for Estrogen/Progesterone Receptor (ER/PR)- positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer patients with 1-3 positive lymph nodes. Physicians completed a questionnaire indicating treatment choice prior to and post availability of RS results. The primary endpoint was change in the physician's recommendation for chemotherapy prior to and post assay results. Secondary endpoints included change in physician's expressed level of confidence, and changes in estimated cost of recommended treatments prior to and post assay results. RESULTS: For the entire cohort, physician recommendation for chemotherapy was reduced by an absolute 67.1% by knowledge of the RS assay result (P < .0001). Physician recommendation of chemotherapy was decreased by 75.9% for patients RS result <14 (P < .0001); and 67.5% for patients with RS result 14-25 (P < .0001). Changes in treatment recommendations were associated with an overall reduction in cost by 73.7% per patient, and after incorporating the cost of the RS test, a cost benefit of $823 CAN at 6-month follow-up. CONCLUSION: Altogether, we established that the assay led to a two-third reduction in the use of chemotherapy, and was a cost-effective approach for hormone receptor-positive, node-positive breast cancer.

The impact of systematic assessment for adverse events on unscheduled hospital utilization in patients receiving neoadjuvant or adjuvant chemotherapy: A retrospective multicenter study.

BACKGROUND: This study was conducted to compare the reported adverse event (AE) profiles and unexpected use of medical services during chemotherapy between before and after the healthcare reimbursement of AE evaluation in patients with cancer. PATIENTS AND METHODS: Using the electronic medical record database system, extracted patients with breast, lung, gastric, and colorectal cancers receiving neoadjuvant or adjuvant chemotherapy between September 2013 and December 2016 at four centers in Korea were matched using the 1:1 greedy method: pre-reimbursement group (n = 1084) and post-reimbursement group (n = 1084). Unexpected outpatient department (OPD), emergency room (ER) visit, hospitalization rates, and chemotherapy completion rates were compared between the groups. RESULTS: The baseline characteristics were well-balanced between the groups. By chemotherapy cycle, hospitalization (1.8% vs. 2.3%; p = 0.039), and ER visit rates (3.3% vs. 3.9%; p = 0.064) were lower in the post-reimbursement group than that in the pre-reimbursement group. In particular, since cycle 2, ER visit and hospitalization rates were significantly lower in the post-reimbursement group than those in the pre-reimbursement group (2.6% vs. 3.3%; p = 0.020 and 1.4% vs. 2.0%; p = 0.007, respectively), although no significant differences were observed during cycle 1. The OPD visit rates were similar between both groups, regardless of cycles. The post-reimbursement group had a higher proportion of patients who completed chemotherapy as planned than the pre-reimbursement group (93.5% vs. 90.1%; p = 0.006). Post-reimbursement group had more AEs reported, including alopecia, fatigue, diarrhea, anorexia, and peripheral neuropathy, during cycle 1 than the pre-reimbursement group, which significantly decreased after cycle 2. CONCLUSION: The introduction of healthcare reimbursement for AE evaluation may help physicians capture and appropriately manage AEs, consequently, decreasing hospital utilization and increasing chemotherapy completion rates.

Eficacia y seguridad de dasatinib en pacientes adultos con leucemia linfoblástica aguda philadelphia positivo resistente o intolerante a quimioterapia más imatinib / Efficacy and safety of dasatinib in adult patients with philadelphia-positive acute lymphoblastic leukemia resistant or intolerant to chemotherapy plus imatinib

ANTECEDENTES : El presente dictamen expone la evaluación de la eficacia y seguridad de dasatinib con o sin quimioterapia, comparado con quimioterapia, en pacientes adultos con leucemia linfoblástica aguda, philadelphia positivo, resistente o intolerante a quimioterapia más imatinib. En la literatura se señala que, la leucemia linfoblástica aguda (LLA) cromosoma Philadelphia positivo (Ph+) representa entre el 20.0 al 30 % de los casos de LLA. En el Perú, no se conoce el número de casos de LLA Ph+; sin embargo, se conoce que, en el 2019, la tasa de incidencia de LLA en personas mayores de 20 años fue de 1.04 casos por cada 100,000 personas y la tasa de mortalidad fue de 0.79 muertes por cada 100,000 personas.  Luego de la terapia de inducción con un inhibidor de la tirosina quinasa (TKI, por sus siglas en inglés), entre el 10 y 20 % de los pacientes desarrolla LLA resistente. Debido a la aparición de casos de resistencia o intolerancia a los TKI de primera generación (imatinib), se han desarrollado otros TKI, como dasatinib. En EsSalud, se cuentan con varias opciones de medicamentos que pueden ser empleados en diferentes esquemas de quimioterapia en este grupo de pacientes con resistencia o intolerancia a TKI. Actualmente, dasatinib se encuentra disponible en EsSalud para el tratamiento de pacientes con leucemia mieloide crónica (LMC), Ph+ resistente o intolerante a tratamientos previos a dosis altas a imatinib y sin mutación T315l. No obstante, algunos especialistas de EsSalud solicitan que se amplíe el uso de dasatinib a pacientes adultos con LLA Ph+ resistente o intolerante, aduciendo que dasatinib (con o sin quimioterapia) podría mejorar la sobrevida libre de progresión (SLP) del paciente. Así, el presente dictamen preliminar expone la evaluación de la eficacia y seguridad de dasatinib, con o sin quimioterapia, en pacientes adultos con LLA Ph+ resistente o intolerante a quimioterapia más imatinib. METODOLOGÍA: Tras la búsqueda de la literatura científica, se identificaron dos guías de práctica clínicas (GPC) elaboradas por The National Comprehensive Cancer Network (NCCN) y The European Society for Medical Oncology (ESMO), y dos evaluaciones de tecnologías sanitarias (ETS) elaboradas por The Scottish Medicines Consortium (SMC) y Comissão Nacional de Incorporação de Tecnologías no Sistema Único de Saúde (CONITEC). Además, se encontraron dos estudios de fase II; sin grupo de comparación, el estudio START-L (Ottman et al., 2007), empleado para sustentar la aprobación acelerada de uso de dasatinib por parte de la Food and Drug Administration (FDA) y la aprobación de la European Medicines Agency (EMA) en pacientes con LLA Ph+ y resistencia o intolerancia a una terapia previa, y el estudio de Sakamaki et al., 2009. RESULTADOS: Se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad. CONCLUSIONES: En el presente documento, se evaluó la mejor evidencia científica disponible hasta la actualidad, sobre la eficacia y seguridad de dasatinib con o sin quimioterapia, comparado con quimioterapia, en pacientes adultos con LLA Ph+y resistencia o intolerancia a la quimioterapia más imatinib. La búsqueda sistemática de la evidencia culminó con la selección de dos GPC (NCCN 2021; Hoelzer et al. 2016), dos ETS (CONITEC 2020; SMC 2007), el estudio de fase II START-L, pivotal de dasatinib (Ottmann et al. 2007), y el estudio de fase II de Sakamaki et al. (Sakamaki et al. 2009). Las GPC del NCCN y ESMO coinciden en señalar que la evidencia disponible sobre el uso de dasatinib para el tratamiento de los pacientes con LLA Ph+ y resistencia o recaída no es de calidad. Por ello, la ESMO resalta que no hay una terapia estándar de reinducción y el NCCN recomienda, especialmente, la participación en un ensayo clínico. Las ETS del SMC y del CONITEC coinciden en dar una recomendación en contra del uso de dasatinib en pacientes con LLA Ph+ con resistencia/recaída a una terapia previa o al mesilato de imatinib. La SMC basó en que la terapia con dasatinib no sería costo-efectiva en este grupo de pacientes; y la CONITEC, en la alta incidencia de EAS, y las altas tasas de abandono del tratamiento y de reducción de dosis observadas en la evidencia analizada. Los estudios START-L y de Sakamaki et al., de fase II, presentaron limitaciones (e.g. falta de un grupo de comparación, pequeño tamaño de la muestra y la falta de acceso al protocolo del estudio) que afectan la validez de sus resultados. Aun así, sus resultados sugieren que el perfil de seguridad de dasatinib no puede ser considerado como favorable para los pacientes (altas tasas de eventos adversos, reducción de dosis de dasatinib y descontinuación del tratamiento). Actualmente, en EsSalud, se cuentan con varias opciones de medicamentos que pueden ser empleados en diferentes esquemas de quimioterapia para pacientes con LLA Ph+ resistente o intolerante a quimioterapia más imatinib. Por lo expuesto, el IETSI no aprueba el uso de dasatinib con o sin quimioterapia en pacientes adultos con LLA Ph+ resistente o intolerante a quimioterapia más imatinib.

Real-world anticancer medications for reproductive-age women with breast cancer by using a claims database in Japan.

Aim: To describe real-world breast cancer medications among reproductive-age women. Patients & methods: Using data from a Japanese claims database, anticancer prescriptions were classified into seven categories of amenorrhea risk based on fertility preservation guidelines. Results: We identified 2999 women with records of breast cancer and anticancer prescription from 2005 to 2018. The proportions of prescriptions were as follows: high, 4.1-12.9%; intermediate: 6.0-16.3%; low: 0.4-2.3%; very low/no: 0.3-12.2%; unknown: 33.9-45.5%; unlisted combination: 12.2-23.4%; and unlisted drug: 12.5-26.7%. The common drugs in the unknown category were trastuzumab (n = 1527), docetaxel (n = 1014), and paclitaxel (n = 995). For medications unlisted in the guidelines, various drugs and drug combinations were observed. Conclusion: Numerous anticancer drugs are currently being prescribed with insufficient evidence regarding amenorrhea risk.

Lay abstract The ability to have children for breast cancer patients is one of the key issues of cancer survivorship, especially because recent progress in anticancer treatments has enabled patients to achieve longer survival. The fertility preservation guidelines of the American Society of Clinical Oncology (2006) introduce some anticancer treatments that carry potential risks to future fertility. In this study, the anticancer prescriptions of 2999 patients with breast cancer aged between 15 and 49 years were examined. Results showed that several medications are prescribed despite the lack of information on the risk of infertility. This suggests that further research is required to fill the evidence gap, and that decision aid through adequate counseling should be undertaken.

The efficacy of oxaliplatin combination adjuvant chemotherapy for elderly patients with stage III colorectal cancer.

Now we are facing to aging society. We aimed to determine the long-term outcomes receiving adjuvant chemotherapy among elderly patients with stage III colorectal cancer. Elderly patients (≧65 years, n=91) diagnosed as stage III colorectal cancer and received adjuvant chemotherapy were retrieved from the database and classified into two groups according to whether the patient received monotherapy (n=65) or doublet therapy(n=26). Recurrence-free survival and overall survival were compared between the groups. To balance the essential variables, we conducted propensity score matching. After one-to-one propensity score matching, each group consisted of 22 patients. No significant difference was detected by comprehensive geriatric assessment 7. Overall survival was significantly longer in the monotherapy group. Adverse events occurred more frequently in the doublet therapy group. Monotherapy may improve the long-term outcome of elderly patients while the adverse events were less frequent.

Toxicity after adjuvant therapy for stage III uterine cancer.

OBJECTIVE: The optimal adjuvant therapy for stage III endometrial cancer is unknown. Studies have suggested that combination therapy with chemotherapy and radiation is associated with improved survival. We examined early and late-term toxicities associated with chemotherapy (CT), external beam radiotherapy (RT), or combination chemoradiotherapy for stage III uterine cancer. METHODS: The SEER-Medicare database was used to identify women age ≥ 65 years with stage III uterine cancer who received adjuvant CT, RT, or chemoradiotherapy from 2000 to 2015. The associations between therapy and early and late-term toxicities identified with billing claims, hospitalizations and emergency department visits were examined using multivariable regression models. RESULTS: A total of 2185 patients were identified including 574 (26.3%) who received CT, 636 (29.1%) who received RT, and 975 (44.6%) who received chemoradiotherapy. The proportion of patients receiving chemoradiotherapy or CT increased over time. During the first 6 and 12 months of adjuvant therapy, RT was associated with a lower risk of early-term toxicity compared to chemoradiotherapy (aRR = 0.59, 95%CI 0.49-0.70 and aRR = 0.76, 95%CI 0.67-0.86, respectively) while CT shared a similar risk of early toxicities as chemoradiotherapy. CT and RT shared a similar risk of late-term toxicities compared to chemoradiotherapy. CT and RT alone were associated with a higher hazard for overall mortality than chemoradiotherapy (aHR = 1.27, 95% CI 1.10-1.47 and aHR = 1.25, 95% CI 1.08-1.44, respectively). CONCLUSION: Chemoradiotherapy is associated with lower mortality compared to single modality therapy and has a similar risk of early and late term toxicities compared to CT, though higher risk of early toxicities compared to RT.

Assessment of Duration and Effects of 3 vs 6 Months of Adjuvant Chemotherapy in High-Risk Stage II Colorectal Cancer: A Subgroup Analysis of the TOSCA Randomized Clinical Trial.

Importance: The addition of oxaliplatin to the standard 6-month fluorouracil-based adjuvant chemotherapy in stage II colorectal cancer has been reported to reduce the risk of relapse although it does not increase survival. The Three or Six Colon Adjuvant (TOSCA) trial compared 3 months with 6 months of adjuvant fluoropyrimidine and oxaliplatin-based chemotherapy in patients with stage III colon cancer. The utility remains unknown. Objective: To assess the noninferiority and toxic effects of 3 vs 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) adjunct chemotherapy among patients with high-risk stage II resected colorectal cancer enrolled in the TOSCA trial. Design, Setting, and Participants: The TOSCA study was a noninferiority phase 3 randomized clinical trial conducted from June 2007 to March 2013 in 130 Italian centers. Included patients had resected colorectal cancer located 12 cm from the anal verge by endoscopy or above the peritoneal reflection at surgery. In this preplanned study assessing the per-protocol population, 5-year relapse-free survival was evaluated in 1254 patients with high-risk stage II resected colorectal cancer who had received adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin). Interventions: Patients were originally randomized (1:1) in the TOSCA trial to receive 3 months (experimental group) or 6 months (control) of standard doses of FOLFOX or CAPOX at the discretion of the treating physician. Main Outcome and Measures: A hazard ratio of at least 1.2 between the 3-month and 6-month chemotherapy groups was set to reject the null hypothesis of noninferiority. Results: Overall, 1254 patients (mean [SD] age, 62.4 [9.8] years; 565 women [45.1%]) with clinical high-risk stage II resected colorectal cancer were analyzed at a median follow-up of 62 months (interquartile range, 53-71) months. Of them, 301 patients (24.0%) had pT4N0M0 tumors, and the remaining 953 patients (76.0%) had high-risk pT3N0M0 tumors; 776 patients (61.9%) received FOLFOX and 478 (38.1%) received CAPOX. The 5-year relapse-free survival was 82.2% for the 3-month arm and 88.2% for the 6-month arm, with an estimated hazard ratio of 1.41 (95% CI, 1.05-1.89; P = .86 for noninferiority). For CAPOX, the 5-year relapse-free survival was similar in the 2 arms (difference, 0.76% favoring the 6-month arm; 95% CI, -6.28% to 7.80%), whereas for FOLFOX, the difference was pronounced: 8.56% in favor of the longer-duration arm (95% CI, 3.45%-13.67%). Nevertheless, the test for an interaction between duration and regimen was not statistically significant. Neurotoxicity was approximately 5 times lower in the shorter duration arm than in the longer duration arm. Conclusions and Relevance: In the 3-month arm, the treatment was significantly less toxic than in the 6-month arm. Noninferiority was not shown for 5-year relapse-free survival. However, a possible regimen effect was observed, suggesting that either 3 months of CAPOX or 6 months of FOLFOX therapy can be used whenever an oxaliplatin doublet is indicated for treatment of patients with stage II colorectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT0064660.

Long-Term Favorable Effects of Physical Exercise on Burdensome Symptoms in the OptiTrain Breast Cancer Randomized Controlled Trial.

Purpose: We evaluate longitudinal changes in symptom clusters and core burdensome symptoms in breast cancer patients who participated in the OptiTrain trial. Methods: 240 women were randomized to 16 weeks of supervised exercise (RT-HIIT or AT-HIIT) or usual care (UC) during adjuvant chemotherapy. Symptom clusters were composed using the Memorial Symptom Assessment Scale (MSAS), assessed at baseline, 16 weeks and 12 months later. Three symptom clusters were formed. Results: Three symptom clusters were identified: "emotional," "treatment-related toxicity," and "physical," with core burdensome symptoms present over time. At 16 weeks, the reported burdens of "feeling sad" (RT-HIIT vs UC: effect size [ES] = -0.69; AT-HIIT vs UC: ES = -0.56) and "feeling irritable" (ES = -0.41 RT-HIIT; ES = -0.31 AT-HIIT) were significantly lower in both intervention groups compared with UC. At 12 months, the AT-HIIT group continued to have significantly lower scores for the core burdensome symptoms "feeling sad" (ES = -0.44), "feeling irritable" (ES = -0.44), and "changes in the way food tastes" (ES = -0.53) compared with UC. No between-group differences were found for physical symptoms. Conclusion: We identified 3 symptom clusters in breast cancer patients during and after adjuvant chemotherapy, composed of "emotional," "treatment-related toxicity," and "physical" symptoms. After treatment completion up to 12 months post-baseline, patients in the physical exercise groups reported lower symptom burden scores for emotional symptoms, compared with UC. Our findings indicate a preserved and long-term beneficial effect of physical exercise on self-reported emotional well-being in chemotherapy-treated breast cancer patients.

Incidence and Management of Diarrhea With Adjuvant Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.

BACKGROUND: The APHINITY (BIG 4-11) study showed that pertuzumab significantly improved the rates of invasive disease-free survival among patients with human epidermal growth factor receptor 2 (HER2)-positive, operable breast cancer when added to adjuvant trastuzumab and chemotherapy. Because diarrhea was a common adverse event that could compromise treatment administration, we evaluated the incidence and management of diarrhea in the APHINITY study. PATIENTS AND METHODS: The APHINITY trial is a prospective, randomized, multicenter, multinational, double-blind, placebo-controlled trial. The eligible patients were randomly assigned to receive standard adjuvant chemotherapy and 1 year of trastuzumab combined with pertuzumab or placebo. The diarrhea incidence, severity (National Cancer Institute common terminology criteria for adverse events, version 4.0), onset, and management were analyzed. RESULTS: A total of 4805 patients were randomized. Diarrhea of any grade was the most common adverse event and occurred in 71% of patients in the pertuzumab arm versus 45% in the placebo arm. Diarrhea grade 3 to 4 was observed in 10% and 4% in the pertuzumab and placebo arms, respectively. The greatest incidence of diarrhea was reported during the concomitant administration of HER2-targeted therapy and taxane (61% vs. 34% of patients experienced an event with pertuzumab vs. placebo, respectively). A marked decrease was observed on chemotherapy cessation. Antidiarrheal agents were commonly used, and diarrhea rarely caused treatment dose modifications or discontinuation. CONCLUSION: Diarrhea was a common adverse event in the APHINITY study. Most episodes were low grade and were generally manageable with common antidiarrheal agents. The incidence of diarrhea was greater with the combination of a taxane and HER2-targeted treatment and decreased once chemotherapy was stopped.

Sense of coherence and health-related quality of life in patients with neurotoxicity after cancer chemotherapy: Assessment from a real-time mobile phone-based system.

OBJECTIVE: In the present study, we aimed to assess sense of coherence (SOC) and health-related quality of life (HRQOL) during and after adjuvant chemotherapy by mobile phone-based reporting in patients with colorectal cancer experiencing neurotoxicity. METHODS: In this prospective descriptive cohort study, a mobile phone-based system was used to receive a series of real-time longitudinal patient-reported assessments of SOC (13-item), HRQOL (Functional Assessment of Cancer Therapy-General (FACT-G) 27-item), and neurotoxicity (OANQ 29-item) from 43 patients with colorectal cancer after being treated with chemotherapy including oxaliplatin. Measurements were conducted during the whole treatment period (mean 5 cycles) and up to 12 months after completing chemotherapy. RESULTS: In total, 817 questionnaire responses (226 SOC, 221 FACT-G, 370 OANQ) answered during and after chemotherapy treatment were available for analysis. Even though all patients experienced neurotoxicity during the treatment period, HRQOL was stable over time. Over time, the ratings of physical wellbeing tended to increase, while the subscale of social wellbeing tended to decrease. Overall SOC, including the three components comprehensibility, manageability, and meaningfulness was stable during the entire study period. No internal data was missing due to the mobile phone-based system. CONCLUSIONS: All patients had neurotoxicity during the treatment period that seemed to affect the social wellbeing component of HRQOL, but SOC seemed unaffected. Real-time patient-reported assessment using mobile phone technology could be valuable in the clinical setting to provide continuous individualised monitoring to help identify patients who need further evaluation to maintain or improve their psychosocial health.

Ambulatory Toxicity Management (AToM) in patients receiving adjuvant or neo-adjuvant chemotherapy for early stage breast cancer - a pragmatic cluster randomized trial protocol.

BACKGROUND: Population-based studies suggest that emergency department visits and hospitalizations are common among patients receiving chemotherapy and that rates in routine practice are higher than expected from clinical trials. Chemotherapy-related toxicities are often predictable and, consequently, acute care visits may be preventable with adequate treatment planning and support between visits to the cancer centre. We will evaluate the impact of proactive telephone-based toxicity management on emergency department visits and hospitalizations in women with early stage breast cancer receiving chemotherapy. METHODS: In this pragmatic covariate constraint-based cluster randomized trial, 20 centres in Ontario, Canada are randomly allocated to either proactive telephone toxicity management (intervention) or routine care (control). The primary outcome is the cluster-level mean number of ED + H visits per patient evaluated using Ontario administrative healthcare data. Participants are all patients with early stage (I-III) breast cancer commencing adjuvant or neo-adjuvant chemotherapy at participating institutions during the intervention period. At least 25 patients at each centre participate in a patient reported outcomes sub-study involving the collection of standardized questionnaires to measure: severity of treatment toxicities, self-care, self-efficacy, quality of life, and coordination of care. Patients participating in the patient reported outcomes (PRO) sub-study are asked to provide written consent to link their PRO data to administrative data. Unit costs will be applied to each per person resource utilized, and a total cost per population and patient will be generated. An incremental cost-effectiveness analysis will be undertaken to compare the incremental costs and outcomes between the intervention and control groups from the health system perspective. DISCUSSION: This study evaluates the effectiveness of a proactive toxicity management intervention in a routine care setting. The use of administrative healthcare data to evaluate the primary outcome enables an evaluation in a real world setting and at a much larger scale than previous studies. TRIAL REGISTRATION: Clinicaltrials.gov , NCT02485678. Registered 30 June 2015.

Eficacia y seguridad del uso de daratumumab más lenalidomida y dexametasona, en comparación con lenalidomida más dexametasona, en el tratamiento de pacientes adultos con mieloma multiple refractarios o en recaída luego de al menos una línea de quimioterapia / Efficacy and safety of the use of daratumumab plus lenalidomide and dexamethasone, compared with lenalidomide plus dexamethasone, in the treatment of adult patients with refractory or relapsed multiple myeloma after at least one line of chemotherapy

INTRODUCCIÓN: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad de daratumumab más lenalidomida y dexametasona, en comparación con lenalidomida más dexametasona, en el tratamiento de pacientes adultos con mieloma múltiple refractario o en recaída luego de al menos una línea de tratamiento. El mieloma múltiple (MM) es una enfermedad caracterizada por una proliferación neoplásica de un clon único de células plasmáticas que producen una inmunoglobulina monoclonal, las cuales se acumulan en la médula ósea. Dicha acumulación lleva a una destrucción ósea masiva, manifestándose en dolor óseo, osteopenia, lesiones osteolíticas y fracturas patológicas. En Perú, se estimó una incidencia anual de 995 casos de MM para el 2018, lo que representaría el 1.7% del total de pacientes con cáncer en el país, según el reporte GLOBOCAN 2018. Las causas del MM son aún desconocidas, se trata de una enfermedad tratable pero que aún no tiene cura. La mediana de sobrevida de los pacientes con MM se encuentra alrededor de 5 años, y la mayoría de los pacientes recibe 4 o más líneas de tratamiento a lo largo del curso de la enfermedad. El tratamiento de MM en el caso específico de pacientes en recaída o refractariedad va a depender de diversos factores, entre los cuales se encuentra el tratamiento previo recibido y la tolerabilidad de cada paciente. En la actualidad, el Petitorio Farmacológico de EsSalud cuenta con lenalidomida en combinación con dexametasona para el tratamiento de pacientes con MM en recaída o refractariedad en progresión de enfermedad que hayan recibido al menos una línea de tratamiento previo. En este contexto, se envió al IETSI la solicitud de evaluación de la adición de daratumumab al esquema mencionado, sobre la hipótesis de una posible mayor eficacia del esquema triple (e.g., daratumumab en combinación con lenalidomida y dexametasona) frente al esquema doble (e.g., lenalidomida con dexametasona). Por ello, el presente dictamen tuvo como objetivo evaluar la eficacia y seguridad comparativa de daratumumab en combinación con lenalidomida y dexametasona versus el esquema de solo lenalidomida en combinación con dexametasona en la población mencionada. METODOLOGÍA: Se llevó a cabo una búsqueda de la literatura con respecto a la eficacia y seguridad de daratumumab más lenalidomida y dexametasona, en comparación con lenalidomida más dexametasona, en el tratamiento de pacientes adultos con mieloma múltiple refractario o en recaída luego de la menos una línea de tratamiento en las bases de datos de PubMed, Cochrane Library, el metabuscador TRIPdatabase y el sitio web www.clinicaltrials.gov. Adicionalmente, se realizó una búsqueda de evaluaciones de tecnologías y guías de práctica clínica en las páginas web de grupos dedicados a la investigación y educación en salud en general como The National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), Scottish Medicines Consortium (SMC), Instituto de Evaluación de Efectividad Clínica y Sanitaria (IECS), Instituto de Evaluación de Tecnología en Salud (IETS); y centros especializados en oncología como European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN) y American Society of Clinical Oncology (ASCO). RESULTADOS: De acuerdo con la pregunta PICO, se llevó a cabo una búsqueda de evidencia científica relacionada al uso de daratumumab más lenalidomida y dexametasona, en comparación con lenalidomida más dexametasona, en el tratamiento de pacientes adultos con mieloma múltiple refractario o en recaída luego de al menos una línea de tratamiento. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (GPC, ETS, RS, MA y ECA fase III). CONCLUSIONES: El presente dictamen expone la evidencia relacionada a la eficacia y seguridad del uso del esquema triple de daratumumab en combinación con lenalidomida y dexametasona, en comparación con el esquema doble de solo lenalidomida más dexametasona en el tratamiento de pacientes con MM en recaída o refractarios luego de al menos una línea de tratamiento previo. La evidencia identificada para la presente evaluación corresponde a cuatro GPC (NICE, ESMO, NCCN y ASCO), cuatro ETS (NICE, SMC, CADTH e IQWiG) y un ECA de fase III. Dos de las cuatro GPC identificadas (ASCO y NCCN) recomiendan el uso de un esquema triple por encima de un esquema doble, y dentro de las alternativas de esquema triple recomienda el esquema de daratumumab más lenalidomida más dexametasona. Por otro lado, la GPC de ESMO recomienda esquemas dobles y triples sin un orden jerárquico, y la GPC de NICE recomienda únicamente el esquema doble de lenalidomida con dexametasona. Las recomendaciones sobre el uso del esquema triple con daratumumab se basan en el ensayo clínico de fase III incluido en el presente dictamen, donde, brevemente, solo se observan beneficios en SLP más no en SG ni calidad de vida. De las ETS identificadas que evaluaron el esquema triple con daratumumab, las de SMC y CADTH concluyeron en recomendar su financiamiento dentro de sus determinados contextos, siempre y cuando se cuente con un acuerdo económico con la compañía comercializadora que permita que el esquema sea costo-efectivo para los sistemas de salud correspondientes. Dichas evaluaciones económicas no son extrapolables al contexto de nuestro país, donde no se cuenta con soporte legal para negociaciones de precios. Por otro lado, la ETS de IQWiG concluye que existe un beneficio en términos de SG a favor de daratumumab únicamente para el subgrupo de mujeres, mientras que el beneficio para hombres no ha sido probado; es de notar que debido al diseño del estudio los análisis por subgrupo solo pueden ser considerados exploratorios. Asimismo, el análisis realizado por IQWi no consideró el ajuste por sobrestimación en análisis interinos descrito por Bassler et al. Por último, no se observaron diferencias para los desenlaces de calidad de vida, mientras que se observó una mayor frecuencia de eventos adversos severos asociados al tratamiento con daratumumab. En el ECA de fase III identificado para responder a la pregunta PICO se tiene que no se reportan desenlaces relacionados a la calidad de vida, y se muestran resultados de SG de un análisis interino. Los resultados reportados en el ensayo sobre la SG muestran una ausencia de diferencias estadísticamente significativas entre los brazos de estudio (HR: 0.64; IC95%: 0.40-1.01; p=0.0534, RR: 0.65; IC95%: 0.42-1.01; p=0.056), la cual se acentúa aún más luego de la corrección por sobreestimación en análisis interinos descrita por Bassler et al., 2010 (RR: 0.9; IC95%: 0.59-1.42). Dichos resultados ajustados se condicen con la comunicación corta publicada luego de 3 años de seguimiento, donde no se observan diferencias estadísticamente significativas entre los grupos. Con ello se tiene que, el esquema triple con daratumumab no ha mostrado un beneficio en términos de SG ni calidad adicional al ofrecido por el esquema doble con solo lenalidomida y dexametasona, el cual se encuentra disponible en la institución para el tratamiento de pacientes con MM en recaída o refractariedad previamente tratados. A ello se suma un perfil de seguridad desfavorable para el esquema con daratumumab, donde se observa una mayor ocurrencia de eventos adversos serios y posiblemente menor tolerabilidad por los eventos adversos asociados a la infusión de daratumumab, los cuales no se encuentran en el esquema doble administrado oralmente. Por lo expuesto, el IETSI no aprueba el uso del esquema triple de daratumumab en los pacientes con MM en recaída o refractariedad luego de al menos una línea de tratamiento.

[Assessment of muscular toxicity due to chemotherapy by cardio-pulmonary exercise testing]. / Évaluation de la toxicité musculaire de la chimiothérapie lors d'une épreuve fonctionnelle à l'exercice.

INTRODUCTION: Cardio-pulmonary exercise testing (CPET) is frequently used to assess aerobic capacity, to evaluate respiratory tolerance and to provide prognostic information. Therefore, CPET is often incorporated in the preoperative assessment of cancer patients. This clinical case report presents the preoperative assessment of a patient before thoracic surgery, in whom an important decrease of aerobic capacity was noted, possibly because of muscular toxicity linked to chemotherapy. CASE REPORT: This clinical case concerns a fit, 66-year-old man with a large cell carcinoma of the bronchus. He had received 2 cycles of adjuvant chemotherapy. Subsequently, a left pneumonectomy had been proposed and preoperative assessment performed. CPET showed no further increase in oxygen uptake after the first ventilatory threshold, in spite of increases in carbon dioxide output, minute ventilation and heart rate. Moreover, maximal oxygen uptake was low and there was a decrease of oxygen pulse at maximal effort. CONCLUSION: We suggest that the limitation of effort was due to a limitation of muscular oxygen extraction, which could be explained by possible muscular toxicity due to chemotherapy.

Multi-gene assays: effect on chemotherapy use, toxicity and cost in estrogen receptor-positive early stage breast cancer.

AIM: To assess multi-gene assay (MGA) effects on chemotherapy use, toxicities, recurrences, and costs in estrogen receptor-positive early breast cancer. METHODS: Meta-analysis performed using data from public databases. Results: Studies included 12,202 women. Relative to no testing, chemotherapy use was higher with 12-gene and 70-gene and lower with PAM50 (commercial) and 21-gene MGAs. Overall, 1643 distant recurrences occurred with no testing, declining by 231 (21-gene), 121 (70-gene), 54 (12-gene) and 94 (PAM50); only the 21-gene assay resulted in no risk of increasing the number of distant recurrences. Relative to 'no testing', total cost of care declined only with 21-gene MGA. CONCLUSION: MGAs differ in chemotherapy use and related outcomes for women with estrogen receptor-positive early breast cancer.