Delayed immune-related hepatitis after 24 months of pembrolizumab treatment: a case report and literature review.

Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1) pathway have revolutionized cancer immunotherapy by enhancing the immune system's ability to combat cancer cells. However, this innovative approach comes with a distinctive set of challenges, as these therapies can lead to immune-related adverse events (irAEs) due to their mechanism of action. The most common irAEs involve the skin, gastrointestinal tract, liver, endocrine system, and lungs. These events can range from mild skin rashes to severe colitis, pneumonitis, or even autoimmune organ damage. These adverse effects usually appear with an average of 5-15 weeks from the start of treatment depending on the affected organ. This article presents a case report of a delayed related-mediated hepatitis, after 24 months of treatment with pembrolizumab and almost 3 months after its termination, and a review of the scientific literature on cases of delayed immune-related hepatitis caused by anti-PD1. This case highlights the importance of monitoring patients treated with immune checkpoint inhibitors after cessation as a growing number of patients stop treatment due to achieving durable responses.

Level of adherence to an extravasation protocol over 10 years in a tertiary care hospital.

BACKGROUND: Extravasation of chemotherapy is an undesirable complication related to the administration of antineoplastic therapy. Establishing the real incidence is difficult. Because of the importance of a quick intervention after an extravasation, every hospital should have an extravasation protocol. OBJECTIVES: The purpose of this study was to determine the degree of observance of an extravasation protocol by nursing staff and to determine extravasation incidence. METHODS: This descriptive, longitudinal, retrospective study was set in a tertiary-level hospital. The researchers reviewed 117 extravasation notification forms received by the pharmacy department during a 10-year period. Nursing actuation, particularly observance of the extravasation protocol, was analyzed. FINDINGS: Protocol adherence was 89%. Twelve deviations from the protocol in the application of recommended measures were detected. An antidote was used in 41 patients, and temperature measures were applied in 14 cases. Ninety-nine patients had at least one episode of reported follow-up. No cases of necrosis or skin ulcers were described, except by one patient, who developed a delayed skin ulcer to vinorelbine. Drugs most frequently reported were etoposide, carboplatin, and paclitaxel. Nursing staff should be continuously trained in extravasation protocol because a rapid actuation can prevent skin lesions.

Tratamiento del dolor crónico no oncológico con opiáceos / Non-oncologic chronic pain treatment with opiates

El dolor crónico no oncológico es un trastorno muy frecuente y que causa gran impacto en la vida diaria de quien lo padece. Su incidencia está en aumento debido en gran parte al incremento de la esperanza de vida, ya que la población más afectada es la geriátrica. El dolor de espalda, el dolor derivado de la osteoartritis y el dolor neuropático son los más prevalentes. Para aliviar el dolor crónico no oncológico se utilizan, entre otros analgésicos, los fármacos opioides. Estos se dividen en opioides menores (tramadol, codeína) y opioides mayores (morfina, fentanilo, oxicodona, metadona). Son fármacos muy efectivos contra el dolor, pero también tienen importantes efectos adversos que hay que conocer y evitar en la medida de lo posible. Uno de estos efectos adversos es la capacidad de los opioides de causar dependencia, tolerancia, adicción y otras conductas aberrantes. La terminología alrededor de estos conceptos puede ser a veces confusa. Para evitar la aparición de este tipo de conductas es necesario tomar precauciones y controlar el paciente de forma periódica. Sin embargo, si los profesionales sanitarios toman las medidas necesarias para evitar estos comportamientos, el riesgo de que aparezcan se reduce considerablemente. Por tanto, monitorizar a los pacientes en tratamiento con opiáceos es fundamental para lograr un buen uso de estos fármacos (AU)

Non-oncologic chronic pain is a very common symptom. It causes great impact on daily activities of people who suffer it. The incidence of this type of pain is rising due to the increase in life expectancy. The most affected population is geriatric population. Back pain, osteoarthritic pain and neuropathic pain are the most prevalent types of non-oncologic chronic pain. Opiates, among other analgesic drugs, are used to alleviate this type of pain. Opiates are divided into minor opiates (tramadol, codeine) and major opiates (morphine, fentanyl, oxycodone, methadone). Opiates are very effective to treat pain, but they also have important adverse effects that we must know and try to prevent. One of these adverse effects is the opiates ability to cause dependence, tolerance, addiction and other aberrant behaviors. Terminology of these concepts is sometimes confusing. It is necessary to be careful and control the patient periodically in order to avoid these aberrant behaviors. However, if health professionals take precautions to prevent these behaviors, the risk is considerably reduced. Controlling patients on opiate treatment is essential to achieve a correct use if these drugs (AU)

Dosing of chemotherapy in obese and cachectic patients: results of a national survey.

BACKGROUND: It is not unusual to find obese and cachectic patients in the hematology oncology setting. However, information on dosage in these groups is scarce. OBJECTIVE: The objectives of our study were to explore the dosing strategies applied in the treatment of obese and cachectic cancer patients and to determine whether these strategies are applied in clinical trials. SETTING: Members of the Spanish Group for the Development of Hematology-Oncology Pharmacy (GEDEFO). METHODS: We invited all cancer hospital pharmacists to participate in a survey. MAIN OUTCOME MEASURE: Descriptive statistics of the dosing strategies approaches. RESULTS: We invited 159 eligible hospitals to participate, and 38 responded to the survey. A total of 50 surveys were received: different strategies were applied by different physicians from the same hospital and by hematology and oncology departments. Body mass index was used to define obesity and cachexia in 40 and 30 % of the cases, respectively. Capping the body surface area (BSA) was the approach most commonly followed (64.1 %) in obese patients, whereas no specific approach was adopted in cachectic patients. In hematology patients, the BSA calculation was based on ideal body weight or adjusted body weight in 16.0 % of cases (n = 2) and 50.0 % of cases (n = 6), respectively; in oncology patients, use of adjusted or ideal body weight was negligible. Actual body weight was the main approach in obese patients (35 surveys) and cachectic patients (48 surveys). Creatinine clearance was assessed mainly using the Cockcroft and Gault equation (around 76.0 % of responses). As for clinical trials, 64.1 % of the respondents (n = 25 hospitals) considered the criteria from each clinical trial individually. CONCLUSIONS: Dose adjustments are more frequent in obese patients than in cachectic patients. In cancer oncology patients, dose is adjusted mainly by hematology and hematopoietic cell transplant teams. Capping BSA is the most frequent strategy, followed by calculating actual body weight.

[NON-ONCOLOGIC CHRONIC PAIN TREATMENT WITH OPIATES]. / Tratamiento del dolor crónico no oncológico con opiáceos.

Non-oncologic chronic pain is a very common symptom. It causes great impact on daily activities of people who suffer it. The incidence of this type of pain is rising due to the increase in life expectancy. The most affected population is geriatric population. Back pain, osteoarthritic pain and neuropathic pain are the most prevalent types of non-oncologic chronic pain. Opiates, among other analgesic drugs, are used to alleviate this type of pain. Opiates are divided into minor opiates (tramadol, codeine) and major opiates (morphine, fentanyl, oxycodone, methadone). Opiates are very effective to treat pain, but they also have important adverse effects that we must know and try to prevent. One of these adverse effects is the opiates ability to cause dependence, tolerance, addiction and other aberrant behaviors. Terminology of these concepts is sometimes confusing. It is necessary to be careful and control the patient periodically in order to avoid these aberrant behaviors. However, if health professionals take precautions to prevent these behaviors, the risk is considerably reduced. Controlling patients on opiate treatment is essential to achieve a correct use if these drugs.

Neumonitis intersticial como reacción adversa a inhibidores de mTOR / Interstitial pneumonitis as an adverse reaction to mTOR inhibitors

Introducción: Los inhibidores de mTOR (del inglés mammalian target of rapamycin), sirolimus y everolimus, utilizados como tratamiento inmunosupresor en el trasplante de órganos sólidos, pueden producir efectos adversos graves, como la neumonitis intersticial. Incidencia y presentación clínica: La incidencia de neumonitis intersticial se ha estimado entre el 4 % y el 11 %, aunque podría ser mayor. La mayoría de los casos publicados se ha producido en pacientes trasplantados renales en tratamiento con sirolimus. La presentación clínica es heterogénea, lo que dificulta el diagnóstico. Se acostumbra a observar alteraciones en la tomografía axial computarizada torácica, como opacidades en vidrio deslustrado. La fisiopatología es poco conocida. Sin embargo, se ha observado una mayor incidencia en pacientes con función renal alterada y en pacientes que habían recibido inhibidores de calcineurina previamente. La relación entre aparición de neumonitis y concentraciones plasmáticas de inhibidores de mTOR no está bien definida. Tratamiento: La suspensión del fármaco y la administración de dosis altas de corticoides parecen ser efectivos. Otras alternativas terapéuticas, aunque más discutidas, son la reducción de la dosis del inhibidor de mTOR y el cambio de sirolimus a everolimus. Conclusión: Se debe sospechar de neumonitis iatrogénica en pacientes trasplantados en tratamiento con inhibidores de mTOR y con síntomas respiratorios. Faltan datos concluyentes en cuanto a estrategias de tratamiento. Parece que everolimus podría ser mejor tolerado que sirolimus (AU)

Introduction: mTOR (mammalian target of rapamycin) inhibitors sirolimus and everolimus, used as immunosuppressants in solid organ transplantation, may cause severe adverse effects, such as interstitial pneumonitis. Incidence and clinical presentation: The estimated incidence of interstitial pneumonitis is 4-11% although it may be higher. Most reported cases have occurred in renal transplant recipients treated with sirolimus. Clinical presentation is heterogeneous, which makes diagnosis difficult. Abnormalities, such as ground glass opacities, are often found in computerised axial tomography scans of the chest. Physiopathology is not well-known. However, patients with abnormal renal function and those with previous calcineurin inhibitor treatment display a higher incidence. The relationship between pneumonitis and mTOR inhibitor plasma concentrations is not well defined. Treatment: Drug discontinuation and administration of high doses of corticosteroids seems to be an effective treatment. mTOR inhibitor dose reduction and replacing sirolimus with everolimus are other alternatives, but they are still under discussion. Conclusion: Iatrogenic pneumonitis must be suspected when a transplant recipient being treated with mTOR inhibitors presents respiratory symptoms. There is lack of conclusive data on treatment strategies. It appears that everolimus may be tolerated better than sirolimus (AU)

Interstitial pneumonitis as an adverse reaction to mTOR inhibitors.

INTRODUCTION: mTOR (mammalian target of rapamycin) inhibitors sirolimus and everolimus, used as immunosuppressants in solid organ transplantation, may cause severe adverse effects, such as interstitial pneumonitis. INCIDENCE AND CLINICAL PRESENTATION: The estimated incidence of interstitial pneumonitis is 4-11% although it may be higher. Most reported cases have occurred in renal transplant recipients treated with sirolimus. Clinical presentation is heterogeneous, which makes diagnosis difficult. Abnormalities, such as ground glass opacities, are often found in computerised axial tomography scans of the chest. Physiopathology is not well-known. However, patients with abnormal renal function and those with previous calcineurin inhibitor treatment display a higher incidence. The relationship between pneumonitis and mTOR inhibitor plasma concentrations is not well defined. TREATMENT: Drug discontinuation and administration of high doses of corticosteroids seems to be an effective treatment. mTOR inhibitor dose reduction and replacing sirolimus with everolimus are other alternatives, but they are still under discussion. CONCLUSION: Iatrogenic pneumonitis must be suspected when a transplant recipient being treated with mTOR inhibitors presents respiratory symptoms. There is lack of conclusive data on treatment strategies. It appears that everolimus may be tolerated better than sirolimus.

Prescribing of zoledronic acid in a tertiary outpatient hospital setting.

BACKGROUND: Zoledronic acid (ZA) is an intravenous bisphosphonate approved for the prevention and treatment of cancer skeletal-related events. OBJECTIVE: Our aim was to analyze the prescription patterns of ZA in the cancer outpatient clinic. METHOD: We performed a retrospective chart review of all patients who received at least 1 dose of ZA from January 2009 until December 2010 in our institution. The patients' follow-up period was defined from the administration of the first dose until February 2011. RESULTS: The sample comprised 345 patients: 31.9 % had breast cancer, 14.5 % prostate cancer, 29.0 % multiple myeloma, and 24.6 % other solid tumors. A total of 4,546 doses were administered; 2,749 (60.5 %) without intravenous chemotherapy. 71.1 % of patients with breast cancer, 86 % with prostate cancer, 60 % with multiple myeloma and 44.6 % with other solid tumors, received ZA without intravenous chemotherapy throughout bisphosphonate treatment. Doses were adjusted in one-third of cases. Administration every 4-weeks was the most frequent schedule. Median duration of treatment varied between 15.0 months for breast cancer and 4.2 months for other solid tumors. CONCLUSION: Most of ZA prescriptions in cancer outpatients followed the labeled indications. The percentage of ZA doses administered without intravenous chemotherapy was 60.5 %.