RESUMO
Older adults represent a growing population amongst cancer survivors who require specific consideration given the complex and largely unknown interactions between cancer-related concerns and age-related conditions. The increasing use of geriatric assessment (GA) has enabled oncologists to appropriately assess older patients' overall health status, personalise anti-cancer treatment and improve survival. However, whilst current research and practice focus on improving the management of older adults with cancer in the acute setting, the progress in the field of survivorship research in geriatric oncology is lagging. As cancer survivorship is a continuum, planning for a healthy survivorship should start at the time of cancer diagnosis. GA can play an important role in identifying potential survivorship issues and optimising delivery of survivorship care. A goal-directed, patient-focused geriatric survivorship care plan that involves a multidisciplinary team provides a framework for a personalised delivery of survivorship care in this patient group and there is a need for tailored interventions that support self-management and care integration. Research on the impact of cancer and its treatment on geriatric-specific outcomes needs to be prioritised through global initiatives to encompass a diverse and heterogenous population of adult cancer survivors.
Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Idoso , Neoplasias/diagnóstico , Neoplasias/terapia , Neoplasias/epidemiologia , Sobrevivência , Planejamento de Assistência ao PacienteRESUMO
BACKGROUND: The safety and anti-tumor activity of penpulimab in patients with advanced upper gastrointestinal (UGI) cancers were evaluated in this study. METHODS: Patients with advanced UGI cancers naive to immune checkpoint inhibitors were enrolled in two trials of penpulimab. In the Phase Ia/Ib trial in Australia, patients received penpulimab intravenous infusion of 1, 3 and 10 mg/kg every 2 weeks in dose-escalation phase and 200 mg every 2 weeks in dose-expansion phase. In the phase Ib/II trial conducted in China, patients received 200 mg penpulimab every 2 weeks. Primary endpoints were safety and tolerability for the phase Ia/Ib trial and the objective response rate for the phase Ib/II trial. The safety and efficacy of penpulimab in patients with UGI cancers in these two trials were evaluated. RESULTS: A total of 67 patients with UGI cancers from Australia and China were enrolled in these two trials and had received penpulimab with a median of 6 (1-64) doses. 44.8% of patients experienced at least one treatment-related adverse event (TRAE), and 7.5% of patients experienced a grade ≥3 TRAE. Among 60 patients evaluable for response, the confirmed objective response rates ranged between 11.1 and 26.3% across cohorts for pancreatic cancer, cholangiocarcinoma, gastric or Gastroesophageal junction carcinoma (Gastric/GEJ), and hepatocellular carcinoma. 11/13 (85.0%) responders had ongoing responses at data cutoff date. CONCLUSIONS: Penpulimab monotherapy demonstrated an acceptable safety and encouraged anti-tumor activity in patients with advanced UGI cancers. Further exploration in a large cohort of patients is warranted. TRIAL REGISTRATION: Phase Ia/Ib trial in Australia (NCT03352531) and phase Ib/II trial in China (NCT04172506).
Assuntos
Anticorpos Monoclonais , Neoplasias Gastrointestinais , Inibidores de Checkpoint Imunológico , Anticorpos Monoclonais/efeitos adversos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoglobulina GRESUMO
BACKGROUND: Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population. METHODS: EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m2 (arm A) or 125 mg/m2 (arm B) on days 1, 8, and 15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD), or death. In each arm, the null hypothesis that the median EFS would be ≤ 7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9-8.9; p = 0.188) in arm A vs 8.3 months (90% CI, 6.2-9.7, p = 0.078) in arm B. Progression-free survival, overall survival, and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in arm B. The most frequently reported non-haematological AEs were fatigue (grade [G] 2-3 toxicity occurrence in arm A vs B, 43% and 51%, respectively) and peripheral neuropathy (G2-3 arm A vs B, 19% and 38%, respectively). CONCLUSION: Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m2 was significantly better tolerated with fewer neurotoxicity-related events, representing a more feasible dose to be recommended for older patients with advanced disease. TRIAL REGISTRATION: EudraCT, 2012-002707-18 . Registered on June 4, 2012. NIH ClinicalTrials.gov, NCT02783222 . Retrospectively registered on May 26, 2016.
Assuntos
Albuminas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Albuminas/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/patologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Invasividade Neoplásica , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Prognóstico , Taxa de SobrevidaRESUMO
Chemoradiotherapy regimens for stage III non-small-cell lung cancer (NSCLC) require ongoing evaluation. This South Australian multicentre prospective phase II study evaluated the safety, activity and outcomes of combination oral vinorelbine and cisplatin administered concurrently with radiotherapy for stage III NSCLC. Consecutive eligible patients received two cycles of oral vinorelbine 50 mg/m day 1 (D1), day 8 (D8) and intravenous cisplatin 50 mg/m D1 and D8 in a 21-day cycle. Chemotherapy was administered concurrently with radiotherapy at 60 Gy in 30 fractions, 2 Gy/fraction to the isocentre, all fields treated daily, 5 days a week over 6 weeks using 10 MV photons and three-dimensional conformal radiotherapy. The primary endpoint was to evaluate the progression-free survival (PFS). The secondary end points were safety, response rates and overall survival (OS). Forty-three eligible patients with stage III NSCLC - comprising 21 squamous cell carcinoma, 18 adenocarcinoma and four large cell carcinoma - were studied. Four patients did not complete the treatment. By intention-to-treat analysis, 25% showed a partial response and 65% had stable disease. None achieved a complete response. Of the 39 patients who completed protocol-specified treatment, 11 (28%) showed a partial response and 28 (72%) had stable disease. The median PFS was 25.2 months and the median OS was 48.3 months. Toxicities were manageable and generally mild, with the majority being either grade 1 (n=38) or grade 2 (n=21). Toxicities were mainly of oesophagitis, pneumonitis, fatigue, nausea and dysphagia. Two cycles of chemotherapy with oral vinorelbine and cisplatin administered concurrently with radical radiation had an acceptable toxicity profile and was active in inoperable stage III NSCLC. PFS and OS outcomes were encouraging. This regimen warrants further investigation.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Cisplatino/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
BACKGROUND: Studies showed that vascular endothelial growth factor (VEGF) inhibitors could improve therapeutic efficacy of PD-1/PD-L1 antibodies by transforming the immunosuppressive tumor microenvironment (TME) into an immunoresponsive TME. Ivonescimab is a first-in-class, humanized tetravalent bispecific antibody targeting PD-1 and VEGF-A simultaneously. Here, we report the first-in-human, phase 1a study of ivonescimab in patients with advanced solid tumors. METHODS: Patients with advanced solid tumors were treated with ivonescimab 0.3, 1, 3, 10, 20 or 30 mg/kg intravenously every 2 weeks using a 3+3+3 dose escalation design. Dose expansion occurred at 10 and 20 mg/kg in selected tumor types. The primary objective was to assess the safety and tolerability, and to determine the maximum tolerated dose (MTD). The secondary objectives included pharmacokinetics, pharmacodynamics and preliminary antitumor activity based on Response Evaluation Criteria in Solid Tumors V.1.1. RESULTS: Between October 2, 2019 and January 14, 2021, a total of 51 patients were enrolled and received ivonescimab. Two dose-limiting toxicities were reported at 30 mg/kg. The MTD of ivonescimab was 20 mg/kg every 2 weeks. Grade≥3 treatment-related adverse events (TRAEs) occurred in 14 patients (27.5%). The most common TRAEs of any grade were rash (29.4%), arthralgia (19.6%), hypertension (19.6%), fatigue (17.6%), diarrhea (15.7%) and pruritus (11.8%). The most common grade≥3 TRAEs were hypertension (7/51, 13.7%), alanine aminotransferase increased (3/51, 5.2%), aspartate aminotransferase increased (2/51, 3.9%) and colitis (2/51, 3.9%). Of 47 patients who had at least one postbaseline assessment, the confirmed objective response rate was 25.5% (12/47) and disease control rate was 63.8% (30/47). Among 19 patients with platinum-resistant ovarian cancer, 5 patients (26.3%) achieved partial response (PR). Efficacy signals were also observed in patients with mismatch repair proficient (pMMR) colorectal cancer, non-small cell lung cancer, and both MMR deficient and pMMR endometrial cancer. CONCLUSIONS: Ivonescimab demonstrated manageable safety profiles and promising efficacy signals in multiple solid tumors. Exploration of alternative dosing regimens of ivonescimab monotherapy and combination therapies is warranted. TRIAL REGISTRATION NUMBER: NCT04047290.
Assuntos
Anticorpos Biespecíficos , Neoplasias , Humanos , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Hipertensão/induzido quimicamente , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/uso terapêutico , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular , Neoplasias/tratamento farmacológicoRESUMO
Key Clinical Message: We describe the first case in literature of malignant mesothelioma of the tunica vaginalis that has shown partial response to systemic immunotherapy (ipilimumab-nivolumab) post orchiectomy, warranting further investigation in a trial setting. Abstract: We present a case report of an 80-year-old ex-smoker with a rare diagnosis of metastatic mesothelioma of the tunica vaginalis, managed with immunotherapy. The patient, with no known history of asbestos exposure, presented with a left scrotal mass and pain. Scrotal ultrasound confirmed a large paratesticular mass, and computed tomography (CT) of the chest, abdomen, and pelvis revealed a bilobed mass in the left scrotal compartment without associated inguinal or abdominopelvic lymphadenopathy, and an indeterminate, subcentimeter, bi-basal subpleural nodules. He underwent a left orchiectomy, and histopathology confirmed the diagnosis of a paratesticular mesothelioma. Postoperatively, the patient had a positron emission tomography (PET) scan showing a new right pleural effusion as well as increasing size of the lobar and pleural nodules bilaterally, all metabolically active and suggestive of progressive metastatic disease. The patient was commenced on ipilimumab and nivolumab immunotherapy, a regimen indicated for malignant pleural mesothelioma; however, the efficacy on paratesticular mesothelioma is not known. After 6 months of treatment, the patient demonstrated a partial response to immunotherapy, with a reduction in the size of known pleural nodules and effusion.Literature review suggests that diagnosis requires a high index of suspicion and patients commonly have metastatic disease at the time of diagnosis. Orchiectomy is a common management modality. However, the role, regimen, and benefits of systemic therapy are unclear, warranting further studies investigating management strategies.
RESUMO
Most cancers occur in older people and the burden in this age group is increasing. Over the past two decades the evidence on how best to treat this population has increased rapidly. However, implementation of new best practices has been slow and needs involvement of policymakers. This perspective paper explains why older people with cancer have different needs than the wider population. An overview is given of the recommended approach for older people with cancer and its benefits on clinical outcomes and cost-effectiveness. In older patients, the geriatric assessment (GA) is the gold standard to measure level of fitness and to determine treatment tolerability. The GA, with multiple domains of physical health, functional status, psychological health and socio-environmental factors, prevents initiation of inappropriate oncologic treatment and recommends geriatric interventions to optimize the patient's general health and thus resilience for receiving treatments. Multiple studies have proven its benefits such as reduced toxicity, better quality of life, better patient-centred communication and lower healthcare use. Although GA might require investment of time and resources, this is relatively small compared to the improved outcomes, possible cost-savings and compared to the large cost of oncologic treatments as a whole.
Assuntos
Avaliação Geriátrica , Neoplasias , Humanos , Idoso , Qualidade de Vida , Neoplasias/terapia , Oncologia , PolíticasRESUMO
Background: There is an immunologic rationale to evaluate immunotherapy in the older glioblastoma population, who have been underrepresented in prior trials. The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients with glioblastoma aged 65 years and older. Methods: NUTMEG was a multicenter 2:1 randomized phase II trial for patients with newly diagnosed glioblastoma aged 65 years and older. The experimental arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant nivolumab and temozolomide. The standard arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant temozolomide. The primary objective was to improve overall survival (OS) in the experimental arm. Results: A total of 103 participants were randomized, with 69 in the experimental arm and 34 in the standard arm. The median (range) age was 73 (65-88) years. After 37 months of follow-up, the median OS was 11.6 months (95% CI, 9.7-13.4) in the experimental arm and 11.8 months (95% CI, 8.3-14.8) in the standard arm. For the experimental arm relative to the standard arm, the OS hazard ratio was 0.85 (95% CI, 0.54-1.33). In the experimental arm, there were three grade 3 immune-related adverse events which resolved, with no unexpected serious adverse events. Conclusions: Due to insufficient evidence of benefit with nivolumab, the decision was made not to transition to a phase III trial. No new safety signals were identified with nivolumab. This complements the existing series of immunotherapy trials. Research is needed to identify biomarkers and new strategies including combinations.
RESUMO
PURPOSE: Monepantel is an approved veterinary anthelmintic with a strong safety profile. Preclinical evidence suggests novel mTOR pathway-associated anticancer activity. An open-label Phase I trial assessed tolerability, pharmacokinetics, pharmacodynamics and PET-CT imaging following oral Zolvix® monepantel administration to adults with treatment refractory, progressing and unresectable solid tumors. METHODS: Subjects were scheduled to daily home-based monepantel administration for 28 days in a 3 + 3 dose escalation study (5.0, 25.0 and 62.5 mg/kg bw). RESULTS: Of 41 reported drug-related AEs, 68% were Grade 1 and 24% were Grade 2; 35 AEs related to gastrointestinal effects including very poor palatability. DLT and MTD could not be determined due to early termination. Myelosuppression was not observed at the lowest level tested. Three of four Cohort 1 subjects had reduced mTOR pathway marker p-RPS6KB1 levels in PBMCs and achieved RECISTv1.1 SD by CT; one had progressive bony metastases by FDG-PET. One subject recorded PD on day 28, correlating with no detectable plasma monepantel from day 7. Monepantel sulfone dominated monepantel in pharmacokinetics. Both Cohort 2 subjects withdrew early due to AEs and the trial was terminated. CONCLUSIONS: Short-term 5 mg/kg bw monepantel administration provides a combined steady-state trough plasma monepantel and monepantel sulfone concentration of 0.5 µM. Gastrointestinal AEs including very poor palatability are concerning and suggested to be resolved by future drug product reformulation. RECISTv1.1, p-RPS6KB1 and plasma tumor marker outcomes provide preliminary evidence of anticancer activity.
Assuntos
Aminoacetonitrila/análogos & derivados , Neoplasias/tratamento farmacológico , Drogas Veterinárias/toxicidade , Administração Oral , Adulto , Aminoacetonitrila/administração & dosagem , Aminoacetonitrila/metabolismo , Aminoacetonitrila/farmacocinética , Aminoacetonitrila/toxicidade , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Concentração Inibidora 50 , Masculino , Dose Máxima Tolerável , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sulfonas/metabolismo , Sulfonas/farmacocinética , Sulfonas/toxicidade , Serina-Treonina Quinases TOR/antagonistas & inibidores , Drogas Veterinárias/administração & dosagem , Drogas Veterinárias/farmacocinéticaRESUMO
The COVID-19 pandemic poses a barrier to equal and evidence-based management of cancer in older adults. The International Society of Geriatric Oncology (SIOG) formed a panel of experts to develop consensus recommendations on the implications of the pandemic on several aspects of cancer care in this age group including geriatric assessment (GA), surgery, radiotherapy, systemic treatment, palliative care and research. Age and cancer diagnosis are significant predictors of adverse outcomes of the COVID-19 infection. In this setting, GA is particularly valuable to drive decision-making. GA may aid estimating physiologic reserve and adaptive capability, assessing risk-benefits of either providing or temporarily withholding treatments, and determining patient preferences to help inform treatment decisions. In a resource-constrained setting, geriatric screening tools may be administered remotely to identify patients requiring comprehensive GA. Tele-health is also crucial to ensure adequate continuity of care and minimize the risk of infection exposure. In general, therapeutic decisions should favor the most effective and least invasive approach with the lowest risk of adverse outcomes. In selected cases, this might require deferring or omitting surgery, radiotherapy or systemic treatments especially where benefits are marginal and alternative safe therapeutic options are available. Ongoing research is necessary to expand knowledge of the management of cancer in older adults. However, the pandemic presents a significant barrier and efforts should be made to ensure equitable access to clinical trials and prospective data collection to elucidate the outcomes of COVID-19 in this population.
Assuntos
COVID-19/complicações , Avaliação Geriátrica , Neoplasias/complicações , Neoplasias/terapia , Idoso , COVID-19/epidemiologia , Consenso , Geriatria/normas , Humanos , Oncologia/normas , Neoplasias/radioterapia , Neoplasias/cirurgia , Cuidados Paliativos/métodos , Pandemias , Medição de Risco , Sociedades MédicasRESUMO
Malnutrition is one of the most common physical manifestations of gastrointestinal (GI) cancers and is often under-diagnosed and under-treated. Like cancers, malnutrition occurs more commonly in older adults, with potential negative consequences to quality of life, functional status, tolerance to treatment, and prognosis. Nutritional assessment and management require a proactive and systematic, multi-disciplinary approach. Early assessment, detection, and prompt intervention of cancer-associated malnutrition and cachexia are equally essential to achieve better quality nutritional care for older oncology patients. This article aims to provide an overview of the evidence associated with poor nutrition and outcomes in older adults with GI cancers, and recommends a management approach from a geriatric oncologist's perspective.
Assuntos
Caquexia/terapia , Neoplasias Gastrointestinais/complicações , Desnutrição/terapia , Avaliação Nutricional , Sarcopenia/terapia , Idoso , Caquexia/diagnóstico , Caquexia/etiologia , Neoplasias Gastrointestinais/mortalidade , Humanos , Desnutrição/diagnóstico , Desnutrição/etiologia , Qualidade de Vida , Estudos Retrospectivos , Sarcopenia/etiologiaRESUMO
TITLE: Phase II study of celecoxib with docetaxel chemoradiotherapy (CRT) followed by consolidation chemotherapy docetaxel plus cisplatin with maintenance celecoxib in inoperable stage III nonsmall cell lung cancer. INTRODUCTION: Concurrent CRT has been associated with improvement in absolute 5-year survival by 10% and is the standard of care for inoperable stage III nonsmall cell lung cancer. Preclinical evidence suggests that cyclooxygenase-2 inhibition may increase the efficacy of CRT. METHODS: Patients were treated with CRT (weekly docetaxel at 30 mg/m2 over 6 weeks with concurrent external beam radiotherapy with 60 Gy in 30 fractions) followed by consolidation chemotherapy with docetaxel and cisplatin, each at 75 mg/m2 given 3 weekly for four cycles. Patients were to receive celecoxib 400 mg twice daily during treatment. Prophylactic cranial irradiation (30 Gy in 15 fractions) was offered if there was disease response. RESULTS: Twenty-four patients commenced CRT. Nineteen patients commenced consolidation therapy with 14 patients completing treatment. Twelve patients had treatment with celecoxib. In the total cohort, the median overall survival (mOS) was 21 months and progression-free survival (PFS) was 16 months. Overall response rate was 59% and disease control rate was 82%. Three patient deaths occurred. Significant grade 3/4 toxicity included radiation pneumonitis (17%), febrile neutropenia (17%), infection/sepsis with or with neutropenia (25%) and esophagitis (12.5%). Retrospective analysis of celecoxib versus no celecoxib treatment showed favorable mOS 26.5 versus 17.5 months and PFS 22 versus 16 months, but this did not reach statistical significance. CONCLUSIONS: The activity of this regimen has been demonstrated. Treatment-related toxicity was substantial. The role of celecoxib in addition to CRT could not be demonstrated in this study because of the small number of patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Celecoxib/administração & dosagem , Quimiorradioterapia , Cisplatino/administração & dosagem , Quimioterapia de Consolidação , Irradiação Craniana , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxoides/administração & dosagemRESUMO
AIM: Autologous hematopoietic stem cell transplantation (auto-HSCT) remains an experimental therapy for metastatic breast cancer (MBC) and there is no established protocol for cluster of differentiation 34+ (CD34+ ) hematopoietic progenitor cell (HPC) mobilization with historic studies using growth factors with or without chemotherapy. This study describes the feasibility and kinetics of CD34+ HPC mobilization following a single administration of docetaxel and the pegylated form of recombinant human granulocyte colony-stimulating factor analogue filgrastim (pegfilgrastim). METHODS: The study design was serial measurement of peripheral blood CD34+ HPC in patients with MBC following a single administration of intravenous (IV) docetaxel 100 mg/m2 on day 1 and subcutaneous (SC) pegfilgrastim 6 mg on day 2. RESULTS: Eight patients with MBC were enrolled. The median age was 56 years (range 51-75 years). All patients had human epidermal growth factor receptor 2 (HER2) negative disease and either hormone refractory or negative disease. Three patients had bone only disease, four had visceral organ disease with or without bone involvement and one had locally unresectable disease only. All patients had prior therapy for early-advanced stage disease and prior therapy for MBC included seven patients receiving at least one line of hormone therapy and three having palliative chemotherapy. Six patients recorded a rise in the CD34+ count greater than 20 cells/µL. The median peak level was 40.2 cells/µL (standard deviation = 28.7) occurring on day 9 and with an average duration of 4 days. Overall, treatment was well tolerated with manageable side-effects. CONCLUSION: The single administration of docetaxel and pegfilgrastim was effective in mobilization of CD34+ HPC and peak levels followed a predictable course. This approach needs validation in prospective studies by preparation of auto-HSCT by leukapheresis and quantification of total CD34+ HPC yields.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Taxoides/uso terapêutico , Idoso , Antígenos CD34 , Docetaxel , Estudos de Viabilidade , Feminino , Filgrastim , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Pessoa de Meia-Idade , Polietilenoglicóis , Estudos Prospectivos , Proteínas Recombinantes/uso terapêuticoRESUMO
It is well recognized that the incidence of breast cancer increases significantly with age. Despite this, older people remain under-represented in many clinical trials and their management relies on extrapolation of data from younger patients. Providing an aggressive intervention can be challenging, particularly in less fit older patients where a conservative approach is commonly perceived to be more appropriate. The optimal management of this population is unknown and treatment decision should be personalized. This review article will discuss several controversial issues in managing older adults with early breast cancer in a multidisciplinary setting, including the role of surgical treatment of the axilla in clinically node negative disease, radiotherapy after breast conservation surgery in low-risk tumours, personalizing adjuvant systemic therapy, and geriatric assessments in breast cancer treatment decisions.
Assuntos
Neoplasias da Mama/terapia , Tomada de Decisões , Avaliação Geriátrica , Assistência Centrada no Paciente , Fatores Etários , Idoso , Axila/cirurgia , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Excisão de Linfonodo , Radioterapia AdjuvanteRESUMO
There is an increasing trend towards using oral systemic therapy in patients with cancer. Compared to parenteral therapy, oral cancer agents offer convenience, have similar efficacy, and are preferred by patients, consequently making its use appealing in older adults. However, adherence is required to ensure its efficacy and to avoid compromising treatment outcomes, especially when the treatment goal is curative, or in case of symptomatic/rapidly progressing disease, where dose-intensity is important. This opens a new challenge for clinicians, as optimizing patient adherence is challenging, particularly due to lack of consensus and scarcity of available clinical evidence. This manuscript aims to review the impact of age-related factors on adherence, summarize the evidence on adherence, recommend methods for selecting patients suitable for oral cancer agents, and advise monitoring interventions to promote adherence to treatment.
Assuntos
Adesão à Medicação , Neoplasias Bucais/tratamento farmacológico , Fatores Etários , Humanos , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Frailty increases the risk of adverse health outcomes and/or dying when exposed to a stressor, and routine frailty assessment is recommended to guide treatment decision. The Balducci frailty criteria (BFC) and Fried frailty criteria (FFC) are commonly used, but these are time consuming. Vulnerable Elders Survey-13 (VES-13) score of ≥7, a simple and resource conserving function-based scoring system, may be used instead. This prospective study evaluates the performance of VES-13 in parallel with BFC and FFC, to identify frailty in elderly patients with early-stage cancer. METHODS: Patients aged ≥70 years with early-stage solid tumors were classified as frail/nonfrail based on BFC (≥1 criteria), FFC (≥3 criteria), and VES-13 (score ≥ 7). All patients were assessed for functional decline and death. RESULTS: We evaluated 185 patients. FFC had a 17% frailty rate, whereas BFC and VES-13 both had 25%, with poor concordance seen between the three geriatric tools. FFC (hazard ratio = 1.99, p = .003) and VES-13 (hazard ratio = 2.81, p < .001) strongly discriminated for functional decline, whereas BFC (hazard ratio = 3.29, p < .001) had the highest discriminatory rate for deaths. BFC and VES-13 remained prognostic for overall survival in multivariate analysis correcting for age, tumor type, stage, and systemic treatment. CONCLUSIONS: A VES-13 score of ≥7 is a valuable discriminating tool for predicting functional decline or death and can be used as a frailty-screening tool among older cancer patients in centers with limited resources to conduct a comprehensive geriatric assessment.