Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors / 中华肿瘤杂志

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

A new approach for leptomeningeal metastases: chemotherapy administered through lumbar intrathecal port / Un nuevo abordaje para el tratamiento de las metástasis leptomeníngeas: uso de catéter implantado para el suministro de quimioterapia vía intratecal lumbar

ABSTRACT Background: Intrathecal chemotherapy is a local therapeutic modality used for treatment of leptomeningeal metastases. However, the techniques currently used, i.e. repeated lumbar puncture and Ommaya reservoir, have certain disadvantages. Lumbar intrathecal port (LIP) placement is a relatively novel technique, which has been used for pain management in cancer patients. Objective: To investigate the use of LIP for intrathecal administration of chemotherapeutic agents in patients with leptomeningeal metastases. Methods: Retrospective study of 13 patients treated with intrathecal chemotherapy for secondary leptomeningeal involvement of a primary solid tumor were included in this retrospective study. The patients received intrathecal chemotherapy through a LIP. Results: The patients received a total of 123 intrathecal chemotherapy doses. No grade 3-4 toxicity, technical problem or severe complication developed. During a median of 136 days of follow-up (range, 67-376 days), 12 patients died (92.3%). The treatment resulted in symptom improvement in all patients and self-rated overall health and quality of life improved, compared with baseline. Conclusions: The LIP system, which has been used for intrathecal pain management for decades, appears to offer a safe alternative for intrathecal chemotherapy in patients with leptomeningeal metastases. Further studies are warranted to clarify its potential use in this setting.

RESUMEN Antecedentes: La quimioterapia intratecal es una modalidad terapéutica local utilizada para el tratamiento de metástasis leptomeníngeas. Sin embargo, las técnicas empleadas actualmente, es decir, las punciones lumbares repetidas y el depósito de Ommaya, tienen algunos inconvenientes. La colocación de un puerto intratecal lumbar (LIP) es una técnica relativamente nueva que se ha utilizado para el tratamiento del dolor en pacientes con cáncer. Objetivo: Investigar el uso de LIP para la administración intratecal de agentes quimioterapéuticos en pacientes con metástasis leptomeníngeas. Métodos: Este estudio retrospectivo incluyó un total de 13 pacientes tratados con quimioterapia intratecal por afectación leptomeníngea secundaria de un tumor sólido primario. Los pacientes recibieron quimioterapia intratecal a través de un LIP. Resultados: Los pacientes recibieron un total de 123 dosis de quimioterapia intratecal. No se desarrolló toxicidad de grado 3-4, ni se presentaron problemas técnicos o complicaciones graves. Durante un promedio de 136 días de seguimiento (rango, 67-376 días), murieron 12 pacientes (92,3 %). El tratamiento dio como resultado una mejoría de los síntomas en todos los pacientes. La salud general autoevaluada y la calidad de vida mejoraron en comparación con los valores iniciales. Conclusiones: El sistema LIP que se ha utilizado para el manejo del dolor intratecal durante décadas, parece ofrecer una alternativa segura para la quimioterapia intratecal en pacientes con metástasis leptomeníngeas. Serán necesarios más estudios para determinar su uso potencial en este ámbito.

Carcinomatosis meníngea: presentación de un caso y revisión del tema / Meningeal carcinomatosis: case report and review of the topic

La carcinomatosis meníngea (CM) es una diseminación difusa de células tumorales en el interior del líquido cefalorraquídeo (LCR) y/o las leptomeninges con siembras difusas de tumores metastásicos sobre ellas. Esta enfermedad ocurre en aproximadamenteel 8 por ciento de las neoplasias malignas. En este trabajo se hace referencia a una paciente femenina pre-escolar de 4 años de edad, debutó con una cefalea bifrontal matutina y ocasionales, acompañadas de vómitos que se hicieron cada vez más frecuentes y que la llevaron a la pérdida de peso progresivo, luego se acompañaba de ataxia troncular, en una RMN se evidenció una lesión tumoral de la fosa posterior, que producía hidrocefalia triventricular, fue intervenida quirúrgicamente donde se realizó exéresis total del tumor. La paciente tuvo una evolución postquirúrgica inmediata favorable, pero luego presentó múltiples complicaciones, luego de mejorar se vuelve a estudiar con RMN donde se mostró un engrosamiento difuso de las meninges que por biopsia se confirmó una invasión leptomeningea del tumor primario operado.