Analysis of neutropenia as a predictive factor of the efficacy of trifluridine-tipiracil treatment.

OBJECTIVES: Trifluridine-tipiracil (TAS-102), an oral cytotoxic agent used in adult patients with refractory metastatic colorectal cancer (mCRC), has been associated with neutropenia (chemotherapy-induced neutropenia) (CIN)). MATERIALS AND METHODS: We evaluated the efficacy and safety of TAS-102 in a group of 45 mCRC patients (median age 66 years) in Huelva province, Spain, in a retrospective, multicenter observational study. RESULTS: We showed that the association between TAS-102 and CIN can be used as a predictor of efficacy. 20% (9/45) of patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 had received at least one previous chemotherapy treatment. Overall, 75.5% (34/45) and 28.9% (13/45) had received anti-VEGF and anti-EGFR monoclonal antibodies, respectively. Additionally, 80% (36/45) of patients had received third-line treatment. The mean treatment period, duration of overall survival (OS), and duration of progression-free survival (PFS) were 3.4, 12, and 4 months, respectively. A partial response was seen in 2 patients (4.3%), and disease stabilization was observed in 10 patients (21.3%). Neutropenia was the most frequent grade 3 - 4 toxicity (46.7%; 21/45). Other findings were anemia (77.8%; 35/45), all grades of neutropenia (73.3%; 33/45), and gastrointestinal toxicity (53.3%; 24/45). The dose of TAS-102 needed to be reduced in 68.9% (31/45) of patients, whereas treatment needed to be interrupted in 80% (36/45) of patients. Grade 3 - 4 neutropenia was a positive prognostic factor for OS (p = 0.023). CONCLUSION: A retrospective evaluation shows that grade 3 - 4 neutropenia is an independent predictor of treatment response and survival in patients undergoing routine treatment for mCRC, but this finding needs confirmation in a prospective study.

Effectiveness, safety, and prognostic factors of trifluridine/tipiracil for the treatment of patients with metastatic colorectal cancer in routine clinical practice.

Background: The combination of trifluridine and tipiracil is indicated in patients with metastatic colorectal cancer previously treated or non-candidates to chemotherapy and biological therapies. This study in routine clinical practice aimed to describe the effectiveness and safety of trifluridine and tipiracil and identify prognostic factors in patients with metastatic colorectal cancer in Spain. Methods: This analysis was a retrospective, observational, multicenter study that included patients aged ≥18 years who had received treatment with trifluridine/tipiracil for metastatic colorectal cancer in third- or subsequent lines. Results: Overall, 294 were evaluated. Trifluridine/tipiracilmedian (minimum, maximum) treatment duration was 3.5 (1.0-29.0) months, and 128 (43.5%) patients received subsequent treatments. One hundred (34%) patients showed disease control rate, and the median progression-free survival and overall survival from trifluridine/tipiracil treatment onset were 3.7 and 7.5 months, respectively. The most frequently reported adverse events were asthenia (all grades, 57.9%) and neutropenia (all grades, 51.3%). A 39.1% and 4.4% of the participants had a dose reduction and a treatment interruption due to toxicity. Patients with age ≥65 years, low tumor burden, ≤2 metastasis sites, treatment dose reduction, neutropenia, and ≥6 cycles, had significantly higher overall survival, progression-free survival, and response rate. Conclusions: This real-life study indicates that trifluridine/tipiracil shows effectiveness and safety in treating patients with metastatic colorectal cancer. The results show a profile of metastatic colorectal cancer patients with previously unknown prognostic factors who have a more significant benefit from treatment with trifluridine/tipiracil in routine clinical practice.

Hypophysitis secondary to pembrolizumab: a case report and review of the literature.

Pembrolizumab is a mAb against the programmed cell death protein-1 (PD-1). It has been approved for the treatment of advanced melanoma (unresectable or metastatic) in adults. Side effects associated with the use of anti-PD-1 are usually considered well tolerated; nevertheless, there are immune-related adverse events that may require treatment discontinuation. A 79-year-old man diagnosed with stage IV right scapular melanoma experienced unspecific symptoms and alterations of the hypothalamus-hypophysis axis after six cycles with pembrolizumab. The case was compatible with immune-related hypophysitis. Autoimmune thyroiditis and primary hypophysitis were excluded and toxicity due to pembrolizumab was considered the cause of hypophysitis. Pembrolizumab was discontinued and toxicity was managed with corticosteroids and hormonal replacement therapy (HRT). After 7 months of follow-up, symptoms were controlled with HRT but thyrotropin and corticotropin hormones had not recovered. It was decided not to reintroduce immunotherapy. Although endocrine disorders are common with the use of anti-PD-1, hypophysitis is very rare. However, clinical signs and symptoms can be nonspecific, therefore, it has probably been underdiagnosed. Monitoring hormones before and during the treatment is important for an early diagnosis and also to replace the alterations with HRT to control the symptoms. Hormonal function does not always recover, but it does not mean immunotherapy cannot be restarted and it should be evaluated in every case.

[Analysis of non-scheduled consultations in patients with digestive neoplasms]. / Análisis de consultas no programadas en pacientes con cáncer digestivo.

OBJECTIVE: Non-scheduled consultation is very frequent among patients with cancer, creating alterations and delays in programmed visits. We describe the incidence of non-scheduled consultations in patients with digestive cancer in our hospital. METHODS: Descriptive, prospective, non-interventional study. In a six-month period (May-December 2017), non-scheduled visits were chronologically recorded in the medical oncology consultation of digestive tumours of Hospital Juan Ramón Jiménez de Huelva. We performed a descriptive analysis of the variables collected through the statistical program G-STAT v.2.0. RESULTS: Patients with colon or rectal cancer generated most consultations (68.63%). followed by pancreatic (9.15%) and gastric (5.23%). Most patients had metastatic or advanced stage cancer (59.87%) and were under palliative or symptomatic treatment (58.82%). The most frequent reason for consultation was clinical symptoms (47.05%). followed by information demand (18.30 %). CONCLUSIONS: Non-scheduled consultations in cancer patients are frequent; they cause interference in scheduled consultations and not always resolved satisfactorily. We propose several measures to reduce the number of non-scheduled consultation in oncology.

OBJETIVO: La demanda de asistencia no programada por parte de los pacientes oncológicos es muy frecuente (1,2) y conllevan alteraciones y retrasos en la actividad ya programada. Describimos la incidencia de consultas no programadas en pacientes con cáncer digestivo de nuestro centro. METODOS: Estudio descriptivo, prospectivo y sin intervención. Se recogieron cronológicamente en un periodo de 6 meses (15 de mayo al 14 de diciembre de 2017) y utilizando como fuente la historia clínica de los pacientes, las visitas no programadas atendidas en la consulta de oncología médica de tumores digestivos del Hospital Juan Ramón Jiménez de Huelva. Realizamos un análisis descriptivo de las variables recogidas mediante el programa estadístico G-STAT v.2.0. RESULTADOS: El mayor número de consultas fue realizado por pacientes con cáncer de colon o recto (68,63%), seguidas por los de páncreas (9,15%) y los gástricos (5,23%). La mayoría de los pacientes tenían un cáncer en situación metastásica o avanzada (59,87%) y estaban recibiendo tratamiento paliativo (58,82%) con quimioterapia o sintomático. El motivo de consulta más frecuente fueron los síntomas clínicos (47,05%), seguido por la demanda de información (18,30 %). CONCLUSIONES: Se constata una alta demanda de asistencia no programada por parte de los pacientes con cáncer digestivo, que interfiere con la asistencia programada y no siempre se resuelve satisfactoriamente. Se proponen varias medidas para reducir el número de estas consultas.

A rapid response to pembrolizumab in a patient with metastatic melanoma.

Prognosis for patients with metastatic melanoma stays poor. Recent advances in the field of immuno-oncology increased treatment options for these patients and gave chances for obtaining partial and even complete response, prolonging survival in a subset of patients. Here, we describe a case of a 55-year-old man with multiple melanoma metastases into lungs who showed an extraordinary response to pembrolizumab used as a first-line treatment. The therapy was well tolerated, with no adverse reactions reported.