Eritrodisestesia palmoplantar tras tratamiento perioperatorio con quimioterapia / Palmoplantar erythrodysesthesia after perioperative treatment with chemotherapy

La eritrodisestesia palmoplantar es una reacción adversa que se asocia a la administración de docetaxel y fluoropirimidinas. La actividad de la enzima dihidropirimidina deshidrogenasa (DPD) determina la tasa de catabolismo del 5-Fluorouracilo (5-FU) y está sujeta a variabilidad interindividual y polimorfismo genético. Por tanto, los pacientes con deficiencia de DPD presentan un mayor riesgo de toxicidad. Presentamos el caso de un paciente tratado con docetaxel, oxaliplatino y 5-FU (esquema FLOT) que presentó toxicidad cutánea moderada y del que se sospechó deficiencia de DPD.(AU)

Palmoplantar erythrodysesthesia is an adverse event associated with the administration of docetaxel and fluoropyrimidines. The activity of the enzyme dihydropyrimidine dehydrogenase (DPD) determines the rate of catabolism of 5-Fluorouracil (5-FU) and is subject to interindividual variability and genetic polymorphism. Therefore, patients with DPD deficiency present an increased risk of toxicity. We present the case of a patient treated with docetaxel, oxaliplatin and 5-FU (FLOT scheme) who presented moderate skin toxicity and who was suspected of DPD deficiency.(AU)

Establishment of an acquired lorlatinib-resistant cell line of non-small cell lung cancer and its mediated resistance mechanism

Although lorlatinib, the third generation of echinoderm microtubule protein 4-anaplastic lymphoma kinase (EML4-ALK) tyrosine kinase inhibitor (TKI), overcame the previous generation ALK-TKIs’ drug resistance problems, but the mechanism of lorlatinib resistance remained unclear. Furthermore, optimal chemotherapy for lorlatinib-resistant non-small cell lung cancer (NSCLC) patients was still unknown.MethodsA lorlatinib-resistant NSCLC cell line SNU-2535LR was generated by gradually increasing dose of lorlatinib to crizotinib-resistant cell line SNU-2535 in vitro. To study the resistance mechanism of SNU-2535LR cells, we applied CCK-8 assay to detect the sensitivity of crizotinib and the reverse effect of APR-246, a p53 activator, on lorlatinib-induced resistance and different chemotherapy drugs to SNU-2535LR cells. We also detected the expressions of EML4-ALK-related proteins of SNU-2535LR cells via western blot.Please confirm that author names have been identified correctly and are presented in the right order. (AU)

¿Es el intervalo libre de docetaxel un factor predictivo para el cáncer de próstata resistente a la castración? / Is docetaxel-free interval a predictive factor for castration-resistant prostate cancer?

Objetivo: El cáncer de próstata (CaP) es el segundo tumor sólido más frecuente en los varones y la quinta causa de muerte relacionada con el cáncer. En los estadios avanzados de la enfermedad se administran tratamientos paliativos en lugar de terapias curativas, por lo que, conocer los posibles indicadores predictivos, parece importante. Se revisaron retrospectivamente los pacientes con cáncer de próstata resistente a la castración (CPRC) que recibieron quimioterapia con docetaxel (Dx). El objetivo de este estudio fue investigar si el intervalo libre de Dx podría tener un valor predictivo para el CaP e influir en las terapias secuenciales.Material y métodos: Este ensayo clínico se realizó en 104 pacientes en la Clínica de Oncología de la Universidad de Medeniyet en 2018-2020. Todos los pacientes con CPRC metastásico recibieron Dx como primer tratamiento y fueron sometidos a terapia dirigida al receptor de andrógenos (ARAT, por sus siglas en inglés) tras la progresión de la enfermedad. Se analizó el tiempo hasta la progresión de los pacientes después de la terapia con Dx y los efectos sobre el tratamiento secuencial.Resultados: Posterior al tratamiento con Dx, los pacientes recibieron ARAT (abiraterona [ABI] n: 49 [47,1%] y enzalutamida [ENZ] n: 54 [51,9%]) como tratamiento de segunda línea, excepto un paciente que recibió cabazitaxel. Hubo una relación estadísticamente significativa entre el intervalo libre de Dx y la duración de la respuesta al ARAT (p<0,001). El tiempo de respuesta al tratamiento con ARAT fue <10,5 meses en todos los pacientes con un período de intervalo libre de Dx<9 meses.Conclusiones: Nuestros resultados avalan la hipótesis de que el intervalo libre de Dx puede ser un factor predictivo para el CPRC. El CPRC podría clasificarse como enfermedad sensible al Dx o resistente al Dx en función del intervalo libre de Dx; y la decisión sobre los tratamientos posteriores podría tomarse con base en esta información. (AU)

Objective: Prostate cancer (PCa) is the second most common solid tumor in men and the fifth leading cause of cancer-related death. In advanced stage, palliative treatments are used instead of curative therapies. Therefore, finding predictive indicators seems crucial. Patients with castration-resistant prostate cancer (CRPC) that received Dx chemotherapy have been retrospectively reviewed. The aim of this study was to investigate whether docetaxel (Dx)-free interval could have a predictive value for PCa and influence other sequential therapies.Material and methods: This clinical trial study was performed on 104 patients at Medeniyet University Oncology Clinic in 2018-2020. All CRPC patients had metastases, received Dx as first-line treatment and underwent androgen receptor axis targeted (ARAT) therapy after disease progression. We analyzed patients’ progression time after Dx therapy and the effects on sequential treatment.Results: After Dx therapy, all patients received ARAT (abiraterone (ABI) n: 49 (47.1%) and enzalutamide (ENZ) n: 54 (51.9%)) as a second-line treatment, except for one patient who received cabazitaxel. There was a statistically significant relationship between the Dx-free interval and duration of response to ARAT (P<.001). The response time of ARAT treatment was <10.5 months in all patients whose Dx-free interval period was <9 months.Conclusions: Our findings support the theory that Dx-free interval can be a predictive factor for CRPC. CRPC disease can be classified as Dx-sensitive disease or Dx-resistance disease, based on the Dx-free interval. Decision on subsequent treatments could be made considering this information. (AU)

Evaluación de una vena periférica para quimioterapia intravenosa: un estudio prospectivo observacional / Evaluation of a peripheral vein for intravenous chemotherapy: a prospective observational study

Este estudio tuvo como objetivo evaluar las alteraciones en el tiempo de una vena periférica utilizada para la infusión de quimioterapia en pacientes con cáncer de mama. Es un estudio observacional prospectivo que incluyó pacientes que estaban programados para recibir infusión periférica de quimioterapia. A estos pacientes se les evaluó la primera vena periférica utilizada para la infusión en cinco momentos: antes de la venopunción, después de la extracción del dispositivo al final de la primera infusión de quimioterapia y los días 21, 42 y 63 después de la primera infusión. El resultado primario fue el calibre de la vena, medido en milímetros con un transiluminador Veinlite LEDX® y una cinta métrica. Se inscribieron en el estudio 59 mujeres que recibieron doxorrubicina y docetaxel por primera vez. El tamaño del calibre varió de 2 a 4 milímetros en la línea de base y disminuyó con el tiempo. Durante el período de seguimiento, las venas periféricas de 35 mujeres (59,3%) se midieron a 0 mm el día 63. Las 24 mujeres restantes (40,7%) tuvieron cierta recuperación, pero para 15 de ellas (62,5%) la vena se convirtió en un cordón palpable. La viabilidad de utilizar una vena periférica para realizar quimioterapia disminuyó a medida que avanzaba el tratamiento.(AU)

This study aimed to assess over time alterations of a peripheral vein used for chemotherapy infusion in patients with breast cancer. It is a prospective observational study which included patients who were scheduled to receive peripheral infusion of chemotherapy. These patients had the first peripheral vein used for infusion evaluated in five moments: before the venipuncture, after device removal at the end of the first chemotherapy infusion, and on days 21, 42, and 63 after the first infusion. The primary outcome was the caliber of the vein, measured in millimeters with a Veinlite LEDX® transilluminator and a tape measure. Fifty-nine women receiving doxorubicin and docetaxel for the first time were enrolled to the study. The caliber size varied from 2 to 4 millimeters at baseline, and decreased overtime. During the follow-up period, peripheral veins of 35 women (59.3%) were measured at 0 mm at day 63. The remaining 24 women (40.7%) had some recovery, but for 15 of them (62.5%) the vein became a palpable cord. The feasibility of using a peripheral vein to perform chemotherapy decreased as the treatment progresses.(AU)

Efficacy of nintedanib plus docetaxel in patients with refractory advanced epidermal growth factor receptor mutant lung adenocarcinoma

Background Anti-angiogenic agents are reported to exert clinical activity in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). We evaluated the outcomes of the combination of docetaxel plus nintedanib in refractory NSCLC patients harboring EGFR mutations. Methods We retrospectively analyzed 19 patients with advanced EGFR-mutant NSCLC who had progressed to EGFR tyrosine kinase inhibitors (TKI) and platinum-based chemotherapy receiving docetaxel and nintedanib at 14 Spanish institutions from January 2013 to December 2019. Kaplan–Meier and log-rank tests were used to evaluate progression-free survival (PFS) and overall survival (OS). Results Median age was 58.9 years (range 42.8–81), 73.7% were female. All patients were Caucasian, and 73.7% were never or light smokers. The baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0–1 in 94.7% of patients. All patients had adenocarcinoma. Brain and liver metastases were present in 47.4% and 31.6% of patients, respectively. The most common EGFR mutations were exon 19 deletion (52.6%) and exon 21 L858R mutation (36.8%); 47.4% patients presented the EGFR T790M. 94.8% of the patients had received 2–3 previous treatment lines. Docetaxel was administered at 75 mg/m2/3 weeks to 16 patients, at 60 mg/m2 to 2 patients and at 45 mg/m2 to one patient. Nintedanib was given until disease progression or unacceptable toxicity at 200 mg twice daily except in 2 patients who received 150 mg twice daily and one patient who received 100 mg/12 h. With a median follow-up of 11.4 months (1–38), the median PFS was 6.1 months [95% confidence interval (CI), 4.9–7.3] and the median OS 10.1 months (95% CI 5.9–14.3). The objective response rate (ORR) was 44.4% (23.7–66.8%) and the disease control rate (DCR) 72.2% (49.4–88.5%) (AU)

Long-term outcomes of induction chemotherapy followed by chemoradiotherapy vs chemoradiotherapy alone as treatment of unresectable head and neck cancer: follow-up of the Spanish Head and Neck Cancer Group (TTCC) 2503 Trial

Background Our previous phase-3 study (TTCC 2503) failed to show overall survival advantage of 2 induction chemotherapy (IC) regimens followed by standard concurrent chemoradiotherapy (CRT) over CRT alone in patients with unresectable locally advanced head and neck squamous-cell carcinoma (LAHNSCC). This study described the long-term survival of those patients. Materials and methods Long-term follow-up study of patients with untreated LAHNSCC assigned to IC (three cycles), with either docetaxel, cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CRT, or CRT alone, included in the previous TTCC 2503 trial. Results In the intention-to-treat population (n = 439), the median OS times were 25.4 (95% CI, 16.8–34.4), 26.2 (95% CI, 18.2–36.6) and 25.4 months (95% CI, 17.4–36.0) in the TPF-CRT, PF-CRT and CRT arms, respectively (log-rank p = 0.51). In the per-protocol population (n = 355), patients with larynx–hypopharynx primary tumors treated with IC (TPF or PF) followed by CRT had a longer median PFS than those who received CRT alone. Moreover, patients with ECOG 0 treated with IC (TPF or PF) followed by CRT had a better TTF than those with CRT alone. There were no statistically significant differences in terms of OS, PFS or TTF, according to the tumor load or affected nodes. Conclusion After a long follow-up, the TTCC 2503 trial failed to show the benefit of IC-CRT in unresectable LAHNSCC regarding the primary end point. However, fit patients with ECOG 0 and primary larynx–hypopharyngeal tumors may benefit from the use of IC if administered by an experienced team (AU)

Evaluación del papel de la PET/TC con [68Ga]Ga-PSMA I&T en la evaluación de la respuesta a la terapia con docetaxel en pacientes con cáncer de próstata resistente a la castración / Assessment of the role of Ga-68 PSMA I&T PET/CT in response evaluation to docetaxel therapy in castration resistant prostate cancer patients

OBJETIVO: Ha habido pocos estudios que investiguen el papel de los ligandos de PSMA en la evaluación de la respuesta al tratamiento de los casos de cáncer de próstata (CP) resistente a la castración metastatizado (CRPCm). En el presente estudio nos proponemos evaluar la capacidad del antígeno de membrana específico de la próstata (PSMA) 68Ga-tomografía por emisión de positrones/tomografía computarizada (PET/TC) en la evaluación de la respuesta terapéutica en pacientes bajo terapia de docetaxel para el CP. MATERIAL Y MÉTODOS: Se analizaron retrospectivamente las historias clínicas de todos los pacientes de CRPCm tratados con docetaxel y referidos a nuestro departamento para imagenología TEP/TC 68Ga-PSMA I&T. Se incluyó en el estudio 16 a pacientes (edad media 69 años, rango 52-82 años) con CP resistente a la castración que recibían tratamiento paliativo con docetaxel y que se habían sometido a una PET/TC 68Ga-PSMA. Se realizaron imágenes 68Ga-PSMA I&T PET/TC y se midieron los niveles de antígeno específico de próstata (PSA) al inicio del estudio antes de la administración del docetaxel (PET1) y después de al menos 3 ciclos (rango 4-12) de quimioterapia (PET2). Se realizó una comparación basada en el paciente y en la lesión de los hallazgos del PET2 con los hallazgos del PET1. RESULTADOS: Se encontró que el cambio (disminución) observado en los valores SUVmáx de los ganglios linfáticos y la glándula prostática/lecho prostático después del tratamiento en comparación con el pretratamiento fue estadísticamente significativo (p = 0,033). Tres de 16 pacientes (19%) se clasificaron como enfermedad progresiva (ED), 4/16 (25%) como enfermedad estable (EE), 9/16 (56%) como remisión parcial (RP) radiológicamente. Se observó una tendencia creciente del PSA (TC) en 4 pacientes (25%) y una tendencia decreciente del PSA (DT) en 3 pacientes (18%). Nueve pacientes mostraron una respuesta del PSA del 2% (56%). De los 4 pacientes que mostraron EE, 3 tenían IT, 3 tenían BR. De los 9 pacientes que mostraron RP en los estudios de TEP, 8 pacientes mostraron BR y un paciente mostró DT. CONCLUSIÓN: Las imágenes con 68Ga-PSMA PET/TC mostraron una gran concordancia con la evaluación de la BR en cuanto a los niveles de PSA, especialmente en los pacientes que mostraron una buena respuesta a la terapia. 68Ga-PSMA PET/TC también fue exitoso en la identificación de la enfermedad progresiva en pacientes que mostraron una paradójica disminución de los niveles de PSA

OBJECTIVE: There have been only few studies investigating the role of PSMA ligands in the therapy response assessment of metastasized castration resistant prostate cancer (mCRPC) cases. In this study we aimed at evaluating the capability of 68Ga- prostate-specific membrane antigen (PSMA) I&T positron emission tomography/computerized tomography (PET/CT) in the assessment of therapeutic response in patients under docetaxel therapy for prostate cancer (PCa). MATERIAL AND METHODS: The clinical records of all mCRPC patients treated with docetaxel and referred to our department for 68Ga-PSMA I&T PET/CT imaging were retrospectively analysed. Sixteen patients (mean age 69 years, range 52-82 years) with castration-resistant prostate cancer patients receiving palliative docetaxel therapy and had undergone 68Ga-PSMA I&T PET/CT scan were included in the study. 68Ga-PSMA I&T PET/CT imaging was done and prostate specific antigen (PSA) levels were measured at baseline before administration of docetaxel (PET1) and after at least 3 cycles (range 4-12) of chemotherapy (PET2). Patient-based as well as lesion-based comparison of PET2 findings with PET1 findings were done. RESULTS: The change (decrease) observed in lymph node and prostate gland/prostatic bed SUVmax values after treatment compared to pretreatment was found to be statistically significant (P=.033). 3/16 patients (19%) were classified as progressive disease (PD), 4/16 (25%) as stable disease (SD), 9/16 (56%) as partial remission (PR) radiologically. An increasing PSA trend (IT) was observed in 4 patients (25%) and a decreasing PSA trend (DT) in 3 patients (18%). Nine patients showed a PSA response of ≥ 50% (56%). Of the 4 patients showing SD, 3 had IT, 3 had BR. Of the 9 patients who showed PR on PET studies, 8 patients showed BR and 1 patient showed DT. CONCLUSION: Imaging with 68Ga-PSMA PET/CT showed great concordance with biochemical response evaluation in terms of PSA levels, especially in patients showing good response to therapy. 68Ga-PSMA PET/CT was also successful in identifying progressive disease in patients showing paradoxical decline in PSA levels

Estudio observacional de la toxicidad con diferentes formulaciones de docetaxel en pacientes con cáncer de mama / Observational study of clinical toxicity with different formulations of docetaxel in breast cancer patients

OBJETIVO: Estudiar los excipientes e impurezas de los diferentes medicamentos comercializados de docetaxel y conocer la incidencia de los diversos eventos adversos derivados del uso de docetaxel y su repercusión clínica en pacientes con cáncer de mama en el contexto de adyuvancia o neoadyuvancia. MÉTODO: Estudio observacional, longitudinal, prospectivo y multicéntrico en 26 hospitales de Madrid, Cataluña, Andalucía y Comunidad Valenciana. Se caracterizaron las distintas formulaciones de docetaxel en cuanto a pH, cantidad de docetaxel e impurezas. Se evaluó la incidencia acumulada de eventos adversos de cualquier grado estratificados por tipo de medicamento, analizando las diferencias mediante el test de χ2.RESULTADOS: Se detectaron diferencias estadísticamente significativas entre las distintas formulaciones de docetaxel en cuanto a la incidencia acumulada por ciclo de: modificación de dosis, anemia, reacciones de hipersensibilidad y anafilaxia, neuropatía, toxicidad palmo-plantar y dermatológica, toxicidad ungueal y edema facial. La formulación con un menor contenido en impurezas presentó mejores resultados en modificación de dosis, visitas a urgencias, e incidencia de anemia y edema facial, pero peores en hospitalización, neutropenia febril, neuropatía motora y toxicidad palmo-plantar. CONCLUSIONES: Los resultados muestran diferencias en la incidencia de los eventos adversos de los distintos medicamentos con docetaxel comercializados en nuestro país, con diferencias significativas entre ellos en algunas de las variables estudiadas. No se ha podido identificar un medicamento con un mejor perfil de toxicidad. Tampoco se ha podido establecer su relación con respecto a la composición de excipientes e impurezas

OBJECTIVE: To analyze the excipients and impurities contained in the various docetaxel products available on the market and find out whether they may be responsible for any of the different adverse events associated with the use of docetaxel in patients with breast cancer receiving adjuvant or neoadjuvant treatment. METHOD: This is a prospective, multicenter, longitudinal observational, study carried in 26 hospitals in Madrid, Catalonia, Andalusia, and the Valencia Region. The different docetaxel formulations were characterized in terms of their pH, amount of the active ingredient and impurities. The cumulative incidence of adverse events of any grade was evaluated. Adverse events were stratified by drug type and differences were analyzed by means of a chi-square test. RESULTS: Statistically significant differences were found between the different docetaxel formulations in the cumulative per-cycle incidence of: dosage change, anemia, hypersensitivity reactions and anaphylaxis, neuropathy, palmoplantar and dermal toxicity, ungual toxicity and facia edema. The formulation with the lowest content of impurities showed better results in terms of change of dosage, visits to the emergency room and incidence of anemia and facial edema. However, it was associated with poorer results regarding hospitalization, febrile neutropenia, motor neuropathy and palmoplantar toxicity. CONCLUSIONS: The results of the study showed differences in the incidence of adverse events of the different docetaxel products available in Spain. Such differences were statistically significant for some of the variables analyzed. The study was not able to determine which of the products offered the best toxicity profile. Nor was it possible to establish a correlation with respect to the composition of excipients or the content of impurities

Importancia del radio-223 en la práctica hospitalaria. Visión del oncólogo médico / Relevance of radium-223 in hospital clinical practice from a medical oncologist point of view

Actualmente las opciones de tratamiento disponibles para el cáncer de próstata resistente a la castración metastásico (CPRCm) son diversas, pero carecemos de datos prospectivos sobre la mejor estrategia de secuenciación en estos pacientes. El dicloruro de 223Ra es el primer radiofármaco emisor de partículas alfa que ha demostrado aumento de supervivencia en pacientes con CPRCm. Este fármaco actúa selectivamente sobre el hueso, por lo que existe una ventana de oportunidad para su administración previa al desarrollo de metástasis viscerales, que debe ser tenida en cuenta a la hora de diseñar la estrategia terapéutica de estos pacientes. Es necesario, por tanto, definir los diferentes escenarios disponibles en la práctica clínica con el fin de llevar a cabo una mejor selección de pacientes y su correcta monitorización

Currently, there are several options available for the treatment of metastatic castration resistant prostate cancer (mCRPC), however evidence on the optimal treatment sequence is lacking. 223Ra is the first targeted alpha therapy that has shown an improvement in overall survival in mCRPC patients. This drug specifically targets bone lesions, so there is a window of opportunity for the administration of 223Ra previous to the development of visceral metastases. This should be taken into account to design the therapeutic strategy for mCRPC patients. It is necessary, therefore, to review the different approaches in routine clinical practice, to define best practices for patient selection and on-treatment monitoring