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BACKGROUND: The relationship between CINV duration and recurrence in subsequent cycles is largely unstudied. Our objective was to determine if patients experiencing CINV in their first cycle of chemotherapy (C1) would face increased risk of CINV in later cycles and whether the duration of the CINV would predict increased risk of recurrence. PATIENTS AND METHODS: Using data from a previously reported phase III trial, we assessed patients' recurrence of breakthrough CINV after antiemetic prophylaxis for anthracycline+cyclophosphamide (AC) for breast cancer, comparing C1 short CINV vs. extended CINV as a secondary analysis. Complete response (CR) and CINV duration were primary and secondary endpoints, respectively. CR was considered prophylaxis success; lack of CR was considered treatment failure (TF). RESULTS: Among 402 female patients, 99 (24.6%) had TF in C1 (TF1). The remaining 303 patients (CR1) had ≥93% CR rates in each subsequent cycle, while the 99 patients with TF1 had TF rates of 49.8% for cycles 2-4 (P < .001). The 51 patients with extended TF (≥3 days) in C1 had recurrent TF in 73/105 later cycles (69.5%, P < .001), while the 48 patients with short TF (1-2 days) in C1 had recurrent TF in 33/108 later cycles (30.6%). The relative risk of recurrence after C1 extended TF was 2.28 (CI 1.67-3.11; P < .001) compared to short TF. CONCLUSIONS: Prophylaxis success in C1 led to >90% repeat success across cycles of AC-based chemotherapy. For patients with breakthrough CINV, extended duration strongly predicted recurrent CINV. The duration of CINV should be closely monitored, and augmenting antiemetic prophylaxis considered for future cycles when extended CINV occurs.
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Antieméticos , Antineoplásicos , Humanos , Feminino , Vômito/induzido quimicamente , Vômito/prevenção & controle , Vômito/tratamento farmacológico , Náusea/induzido quimicamente , Náusea/prevenção & controle , Náusea/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Antineoplásicos/uso terapêuticoRESUMO
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV)'s impact on work loss remains poorly described. We evaluated associations between the duration of CINV episodes, CINV-related work loss (CINV-WL), and CINV-related activity impairment (CINV-AI) in patients with breast cancer receiving highly emetogenic chemotherapy. METHODS: We analyzed data from a prospective CINV prophylaxis trial of netupitant/palonestron and dexamethasone for patients receiving an anthracycline and cyclophosphamide (AC) for breast cancer (NCT0340371). Over the observed CINV duration (0-5 days), we analyzed patient-reported CINV-WL and CINV-AI for the first two chemotherapy cycles. We categorized patients as having either extended (≥ 3 days) or short (1-2 days) CINV duration and quantified its impact on work using the Work Productivity and Activity Impairment Questionnaire (WPAI). RESULTS: Overall, we captured data for 792 cycles in 402 women, including 136 (33.8%) employed patients with 35.3% reporting CINV. Of those with CINV, patients reported CINV-WL in 26 cycles and CINV-AI in 142 cycles. Of those with CINV, 55.3% of extended CINV cycles experienced CINV-WL compared to 16.7% of short CINV cycles (p < 0.001). The relative risk of CINV-WL between extended and short CINV was 3.32 (p < 0.01) for employed patients. The mean difference in CINV-AI scores (higher = worse) between extended and short duration CINV was 5.0 vs. 3.0 (p < 0.001). CONCLUSION: Extended (≥ 3 days) CINV was associated with more than triple the risk of CINV-WL and higher CINV-AI compared with short CINV.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Estudos Prospectivos , Vômito/induzido quimicamente , Vômito/prevenção & controle , Náusea/induzido quimicamente , Náusea/prevenção & controle , AntraciclinasRESUMO
The NCCN Guidelines for Hematopoietic Growth Factors provide recommendations for the appropriate use of growth factors in the clinical management of febrile neutropenia (FN), chemotherapy-induced thrombocytopenia (CIT), and chemotherapy-induced anemia (CIA). Management and prevention of these sequelae are an integral part of supportive care for many patients undergoing cancer treatment. The purpose of these guidelines is to operationalize the evaluation, prevention, and treatment of FN, CIT, and CIA in adult patients with nonmyeloid malignancies and to enable the patient and clinician to assess management options for FN, CIT, and CIA in the context of an individual patient's condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for Hematopoietic Growth Factors, with particular emphasis on the incorporation of a newly developed section on CIT.
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Anemia , Antineoplásicos , Neoplasias , Adulto , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Antineoplásicos/efeitos adversos , Fatores de Crescimento de Células Hematopoéticas/uso terapêutico , Humanos , Neoplasias/tratamento farmacológicoRESUMO
Hematopoietic growth factors, including erythrocyte stimulating agents (ESAs), granulocyte colony-stimulating factors, and thrombopoietin mimetics, can mitigate anemia, neutropenia, and thrombocytopenia resulting from chemotherapy for the treatment of cancer. In the context of pandemic SARS-CoV-2 infection, patients with cancer have been identified as a group at high risk of morbidity and mortality from this infection. Our subcommittee of the NCCN Hematopoietic Growth Factors Panel convened a voluntary group to review the potential value of expanded use of such growth factors in the current high-risk environment. Although recommendations are available on the NCCN website in the COVID-19 Resources Section (https://www.nccn.org/covid-19/), these suggestions are provided without substantial context or reference. Herein we review the rationale and data underlying the suggested alterations to the use of hematopoietic growth factors for patients with cancer in the COVID-19 era.
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Management of febrile neutropenia (FN) is an integral part of supportive care for patients undergoing cancer treatment. The NCCN Guidelines for Hematopoietic Growth Factors provide suggestions for appropriate evaluation, risk determination, prophylaxis, and management of FN. These NCCN Guidelines are intended to guide clinicians in the appropriate use of growth factors for select patients undergoing treatment of nonmyeloid malignancies. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines regarding the incorporation of newly FDA-approved granulocyte-colony stimulating factor biosimilars for the prevention and treatment of FN.
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Medicamentos Biossimilares/uso terapêutico , Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Fatores de Crescimento de Células Hematopoéticas/uso terapêutico , Neoplasias/tratamento farmacológico , Guias de Prática Clínica como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medicamentos Biossimilares/economia , Medicamentos Biossimilares/normas , Neutropenia Febril Induzida por Quimioterapia/etiologia , Aprovação de Drogas , Custos de Medicamentos , Educação Médica Continuada , Fatores de Crescimento de Células Hematopoéticas/economia , Fatores de Crescimento de Células Hematopoéticas/normas , Humanos , Oncologia/educação , Oncologia/normas , Neoplasias/sangue , Oncologistas/educação , Organizações sem Fins Lucrativos/normas , Fatores de Risco , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudênciaRESUMO
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis address all aspects of management for chemotherapy-induced nausea and vomiting. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Antiemesis, specifically those regarding carboplatin, granisetron, and olanzapine.
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Antieméticos/uso terapêutico , Vômito/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzodiazepinas/uso terapêutico , Granisetron/uso terapêutico , Humanos , Neoplasias/complicações , Neoplasias/terapia , Olanzapina , Antagonistas da Serotonina/uso terapêutico , Vômito/etiologia , Vômito/prevenção & controleRESUMO
Myeloid growth factors (MGFs) are given as supportive care to patients receiving myelosuppressive chemotherapy to reduce the incidence of neutropenia. This selection from the NCCN Guidelines for MGFs focuses on the evaluation of regimen- and patient-specific risk factors for the development of febrile neutropenia (FN), the prophylactic use of MGFs for the prevention of chemotherapy-induced FN, and assessing the risks and benefits of MGF use in clinical practice.
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Antineoplásicos/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Células Mieloides/metabolismo , Antineoplásicos/uso terapêutico , Humanos , Incidência , Oncologia/métodos , Neoplasias/tratamento farmacológico , Fatores de RiscoRESUMO
Febrile neutropenia, a common side effect of myelosuppressive chemotherapy in patients with cancer, can result in prolonged hospitalization and broad-spectrum antibiotic use, often prompting treatment delays or dose reductions of drug regimens. Prophylactic use of myeloid growth factors (mainly the colony-stimulating factors filgrastim and pegfilgrastim) in patients of heightened risk can reduce the severity and duration of febrile neutropenia. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Myeloid Growth Factors provide recommendations on the use of these agents mainly in the oncology setting based on clinical evidence and expert consensus. This version includes revisions surrounding the issue of timing of pegfilgrastim administration. It also includes new sections on tbo-filgrastim, a recently approved agent that is biologically similar to filgrastim, and the role of myeloid growth factors in the hematopoietic cell transplant setting.
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Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Fatores Estimuladores de Colônias/uso terapêutico , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Doença Crônica , Fatores Estimuladores de Colônias/administração & dosagem , Fatores Estimuladores de Colônias/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Humanos , Neutropenia/tratamento farmacológico , Neutropenia/etiologia , Pré-Medicação , Resultado do TratamentoRESUMO
INTRODUCTION: Bacillus Calmette-Guérin production is limited worldwide with stuttering shortages affecting patient access. Our institution received 50 vials of bacillus Calmette-Guérin labeled for percutaneous administration, and upon discussion with our clinical team and approval by the Pharmacy and Therapeutics Committee we used the percutaneous formulation in place of the intravesical formulation. We report our experience. METHODS: Between February and April 2019 patients were treated with a third of a vial dose either with percutaneous or intravesical bacillus Calmette-Guérin. American Urological Association Symptom Score and Quality of Life survey and an additional 6-question survey (querying presence of suprapubic pain, hematuria, fevers, malaise, skin rashes, testicular/groin pain) were administered. Statistical analyses comparing the 2 groups were performed with SPSS version 22 software. RESULTS: A total of 30 patients with 73 intravesical instillations were evaluated with 34 patients receiving intravesical and 39 percutaneous bacillus Calmette-Guérin. We found no significant differences when comparing intravesical vs percutaneous bacillus Calmette-Guérin groups in terms of American Urological Association Symptom Score (6.1 vs 6.9, p=0.177), Quality of Life score (1.3 vs 1.7, p=0.132), fevers (2.9% vs 0%, p=0.300), hematuria (14.7% vs 2.8%, p=0.075), suprapubic pain (10.1% vs 4.3%, p=0.129), skin rashes (1.4% vs 0%, p=0.307) and feeling of general fatigue and malaise (15.7% vs 8.6%, p=0.126). CONCLUSIONS: Intravesical instillation of percutaneous bacillus Calmette-Guérin appears to be a safe alternative to intravesical bacillus Calmette-Guérin during times of shortage. Development of additional strains, use of alternative intravesical therapies and incentivizing bacillus Calmette-Guérin production through policy change and/or alternative funding may also help avoid bacillus Calmette-Guérin supply shortages in the future.
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BACKGROUND: Methylene blue (MB) dye has been used for lymphatic mapping/sentinel lymphadenectomy (LM/SL) in staging of melanoma and breast cancer. It has been noted to cause skin necrosis, but its more mild adverse effects from intraparenchymal breast injections are not well characterized. METHODS: Patients undergoing LM/SL for breast cancer and melanoma were reviewed, with attention devoted to skin manifestations. Patients undergoing mastectomies were excluded to rule out changes from flap devascularization. All breast patients were injected intraparenchymally. RESULTS: Ninety-five patients underwent MB injection during a nationwide shortage of lymphazurin; 78 for breast cancer and 17 for melanoma, with 51 patients undergoing breast conservation (BCT). There was no frank skin necrosis among any of the patients. Six (11.8%) BCT patients demonstrated inflammatory changes. Four patients developed findings indistinguishable from infectious cellulitis, with two developing skin telangiectasias prior to radiotherapy. Two patients had fat necrosis confirmed at the MB injection site away from the surgical site; one on imaging and one by biopsy. Most symptoms resolved after conservative management. CONCLUSIONS: MB dye may cause cutaneous changes more subtle than previously described. Physicians caring for patients having LM/SL using MB should be aware of these effects so that a proper differential diagnosis can be entertained postoperatively.
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Neoplasias da Mama/cirurgia , Corantes/efeitos adversos , Meios de Contraste/efeitos adversos , Inflamação/induzido quimicamente , Melanoma/cirurgia , Azul de Metileno/efeitos adversos , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/cirurgia , Pele/efeitos dos fármacos , Idoso de 80 Anos ou mais , Celulite (Flegmão)/diagnóstico , Celulite (Flegmão)/microbiologia , Corantes/provisão & distribuição , Diagnóstico Diferencial , Feminino , Humanos , Inflamação/diagnóstico , Pessoa de Meia-Idade , Corantes de Rosanilina/provisão & distribuiçãoRESUMO
Erythropoiesis-stimulating agents (ESAs) are approved as an alternative to blood transfusions for treating anemia secondary to chemotherapy in patients with cancer. Recently, ESAs have been a source of controversy and confusion in the oncology community. This began when two European trials-the Breast Cancer Erythropoietin Survival Trial (BEST) and the Advanced Head-and-Neck Cancer Treated with Radiotherapy (ENHANCE) Study-raised safety concerns about decreased overall survival and increased venous thromboembolic events. In 2004, the United States Food and Drug Administration (FDA) convened its Oncologic Drugs Advisory Committee (ODAC) to review the data and reassess the risks and benefits of ESAs in patients with cancer. On May 10, 2007, ODAC reconvened when five trials (BEST, ENHANCE, AMG-20010103, AMG-20000161, and EPO-CAN-20) showed decreased overall survival. The briefing document noted that studies demonstrating detrimental effects on survival and/or tumor outcomes used an unapproved treatment regimen designed to maintain hemoglobin levels above 12 g/dl. On May 14, 2007, just days after the ODAC reconvened, the Centers for Medicare and Medicaid Services (CMS) released a proposed decision memo for a national coverage determination (NCD) imposing restrictions on ESAs. For health care providers, aspects of the proposed NCD were markedly inconsistent with FDA-approved ESA use and generally were considered ambiguous and unclear. Over objections of several professional associations and members of Congress, on July 30, 2007, CMS posted the final NCD and declared it effective immediately. When compared with FDA-approved labeling and professional society guidelines, the NCD revealed differences in ESA initiation, dosage escalation, dosage reduction, and definition of response. These discrepancies have generated confusion among health care providers, who are struggling over whether they can feasibly provide a dual system of care-one for Medicare patients and another for non-Medicare patients-that is evidence based. With this supplement, we hope to educate health care providers on the issues and challenges associated with policy-guided health care when discrepancies exist between the policy and evidence-based practice; offer guidance on implementing the NCD; and highlight the important role of pharmacists in the process.
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Anemia/tratamento farmacológico , Antineoplásicos/efeitos adversos , Hematínicos/uso terapêutico , Neoplasias/complicações , Anemia/induzido quimicamente , Antineoplásicos/uso terapêutico , Ensaios Clínicos Controlados como Assunto , Medicina Baseada em Evidências , Política de Saúde , Hematínicos/efeitos adversos , Humanos , Medicare/legislação & jurisprudência , Neoplasias/tratamento farmacológico , Farmacêuticos/organização & administração , Guias de Prática Clínica como Assunto , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudênciaAssuntos
Antineoplásicos/efeitos adversos , Fatores Estimuladores de Colônias/uso terapêutico , Febre/prevenção & controle , Síndromes Mielodisplásicas/prevenção & controle , Neoplasias/tratamento farmacológico , Neutropenia/prevenção & controle , Antibacterianos/uso terapêutico , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Fatores Estimuladores de Colônias/efeitos adversos , Fatores Estimuladores de Colônias/economia , Análise Custo-Benefício , Quimioterapia Combinada , Febre/induzido quimicamente , Febre/tratamento farmacológico , Humanos , Síndromes Mielodisplásicas/induzido quimicamente , Síndromes Mielodisplásicas/tratamento farmacológico , Neutropenia/induzido quimicamente , Medição de Risco , Fatores de RiscoRESUMO
Zoledronic acid is a potent bisphosphonate licensed for the treatment of myeloma and bone metastases from solid tumors. Renal deterioration is the most significant toxicity associated with zoledronic acid. We attempted to define the incidence and clinical significance of renal deterioration in patients receiving zoledronic acid and to develop a risk-factor profile for this treatment sequela. This study is a retrospective analysis of all patients who received zoledronic acid at Fox Chase Cancer Center, Philadelphia, Pa, between 1/10/02 and 1/30/04. Data recorded included patient demographics, tumor characteristics, comorbid illnesses, concomitant medications, cancer therapy, number of zoledronic acid doses administered, and serial creatinine measurements. In total, 3,115 evaluable doses of zoledronic acid were administered to 446 patients (median, 4 doses; mean, 6.98 doses; range, 1-28 doses) at a dose of 4 mg over 15 minutes every 3-4 weeks. Of these 446 patients, 42 experienced renal deterioration (median rise in creatinine level, 1.0 mg/dL; range, 0.5-4.4 mg/dL), requiring discontinuation of zoledronic acid therapy in 8 cases. No patient required dialysis and no patient died as a result of zoledronic acid-induced renal dysfunction. On multivariable analysis, predictive factors for the development of renal deterioration were patient age, a diagnosis of myeloma or renal cell cancer, cumulative number of doses, concomitant therapy with a nonsteroidal anti-inflammatory drug, and current or prior therapy with cisplatin. Using these factors, we constructed a predictive model with an area under the receiver operating characteristic curve of 0.75. The incidence of clinically significant renal deterioration in patients treated with zoledronic acid is low.We present a predictive model for decision support when estimating this risk.
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Injúria Renal Aguda/induzido quimicamente , Difosfonatos/efeitos adversos , Imidazóis/efeitos adversos , Neoplasias/tratamento farmacológico , Idoso , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Difosfonatos/farmacocinética , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Feminino , Humanos , Imidazóis/farmacocinética , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Masculino , Modelos Estatísticos , Neoplasias/complicações , Neoplasias/metabolismo , Estudos Retrospectivos , Ácido ZoledrônicoRESUMO
BACKGROUND: Limited data are available regarding the tolerance of anti-epidermal growth factor receptor (EGFR) antibodies among elderly patients with metastatic colorectal cancer (mCRC). We retrospectively reviewed our experience of treating elderly patients with mCRC with these agents between 2004 and 2011. METHODS: Patients with mCRC ≥ 65 years treated with anti-EGFR agents were included in this analysis. We recorded demographic and disease characteristics, treatment regimen and duration, KRAS status, and overall survival (OS). Toxicity evaluation included common hematologic and nonhematologic toxicities seen with these agents. RESULTS: One hundred seventeen patients were included, with a median age at treatment initiation of 73 years (range, 65-86 years), 59% of male sex, 82% with colon primary tumors, and 51% with metastatic disease at presentation. Median time on anti-EGFR treatment was 2.4 months. Older age at treatment initiation was associated with use of anti-EGFR antibody as monotherapy versus combination therapy (P = .0009). Worse performance status (PS) at treatment initiation was associated with a shorter overall survival (OS) (P = .013) and shorter treatment duration (P = .01). The incidence of hematologic/nonhematologic grade ≥ 3 was 36% and 15%, respectively. No association was found between age and presence of grade ≥ 3 toxicity. Longer treatment duration and better PS at treatment initiation were the only factors associated with higher incidence of grade 3 toxicity. CONCLUSION: Our data demonstrate that anti-EGFR antibodies can be used in older patients with mCRC, with toxicity profiles similar to those reported in large phase III studies of younger patients. Advanced age was associated with receipt of anti-EGFR agents as monotherapy but did not impact treatment outcomes in this population.
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Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Retais/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/secundário , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Panitumumabe , Gravidade do Paciente , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Neoplasias Retais/genética , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Proteínas ras/genéticaRESUMO
PURPOSE: Research regarding new pharmacologic findings in regards to the treatment of postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) are discussed. SUMMARY: PONV and PDNV have many important negative outcomes, including medical complications and financial consequences. Great strides in basic research have identified a plethora of mechanisms involved in regulating and processing the emetic reflex, and subsequent development of antiemetic treatments has lessened these burdens. The currently available antiemetic agents are not able to individually ameliorate PONV, so guidelines have been developed that recommend administering a combination of antiemetic treatments from different drug classes as prophylaxis, especially for high-risk patients. Recent research has indicated that due to the unique structural characteristics of palonosetron that impact receptor binding, this 5-HT(3) receptor antagonist has a pharmacokinetic and pharmacologic profile different from other inhibitors within the drug class. Implications of the high affinity, allosteric, and positive cooperative binding properties of palonosetron include longer and tighter binding to the 5-HT(3) receptor, making palonosetron a very efficient antagonist and less likely to be displaced by the binding of serotonin. CONCLUSION: Ongoing research is warranted in order to better prevent and manage PONV and PDNV.