capecitabine
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Tratamiento adyuvante del cáncer de colon estadio III; cáncer colorrectal metastásico; primera línea del cáncer gástrico avanzado con platino; y cáncer de mama localmente avanzado o metastásico con docetaxel tras fracaso de quimioterapia con antraciclina, o en monoterapia tras fracaso de taxano y antraciclina o cuando no sea candidata a más antraciclina.
Contraindicaciones
Absolutas
- Hipersensibilidad a capecitabina, fluorouracilo o a sus excipientes, o antecedente de reacción grave e inesperada a fluoropirimidinas.
- Deficiencia completa de DPD; embarazo o lactancia; leucopenia, neutropenia o trombocitopenia graves; insuficiencia hepática grave; CrCl <30 ml/min; brivudina reciente o concomitante.
Advertencias clínicas
- Realiza prueba genética DPYD antes de iniciar, salvo que el tratamiento sea necesario de inmediato. Evita capecitabina en deficiencia completa de DPD; en deficiencia parcial individualiza según tolerabilidad e intención terapéutica, sin un porcentaje fijo. — OpenFDA, set_id 007e3432-c8aa-2a76-52ba-c346924c08a7
- Controla hemograma antes de cada ciclo y durante el nadir. Aplaza o modifica el ciclo ante mielosupresión; las infecciones y hemorragias pueden ser graves o mortales. — CIMA/AEMPS, ficha técnica 84871
- La sobredosis exige evaluación urgente: administra uridina triacetato dentro de las 96 horas posteriores al final de la administración de la fluoropirimidina. — DailyMed, capecitabine tablets
Interacciones medicamentosas
- ModeradaBrivudina
Mecanismo: La inhibición de DPD puede provocar toxicidad fluoropirimidínica mortal.
Recomendación: Deja al menos 4 semanas entre brivudina y capecitabina. Brivudina puede iniciarse 24 horas después de la última dosis de capecitabina.
CIMA/AEMPS, ficha técnica 84871
- SeveraAnticoagulantes cumarínicos
Mecanismo: Capecitabina puede aumentar de forma marcada y tardía el INR y el riesgo hemorrágico.
Recomendación: Controla INR con frecuencia durante el tratamiento y después de finalizar; ajusta el anticoagulante.
CIMA/AEMPS, ficha técnica 84871
- SeveraFenitoína
Mecanismo: Capecitabina puede aumentar las concentraciones de fenitoína.
Recomendación: Controla concentraciones y toxicidad y ajusta la fenitoína si es necesario.
CIMA/AEMPS, ficha técnica 84871
- SeveraÁcido folínico o ácido fólico
Mecanismo: Pueden aumentar la toxicidad de capecitabina.
Recomendación: Usa solo dentro de un protocolo definido e intensifica la vigilancia de toxicidad.
CIMA/AEMPS, ficha técnica 84871
- SeveraAlopurinol
Mecanismo: Puede reducir la eficacia de capecitabina.
Recomendación: Evita la administración concomitante.
CIMA/AEMPS, ficha técnica 84871
Embarazo y lactancia
Está contraindicada durante el embarazo y la lactancia. Realiza una prueba de embarazo antes de iniciar. Las mujeres deben usar anticoncepción eficaz durante el tratamiento y durante 6 meses después; los hombres durante el tratamiento y durante 3 meses después. No amamantes durante el tratamiento ni durante 1 semana después.
Bibliografía reciente (PubMed)
Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.
There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507 . Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy.[1] It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence. some have suggested a period of 24 hours before resuming nursing,[2] although the manufacturer recommends an abstinence period of 2 weeks. Capecitabine is metabolized to fluorouracil. Limited information indicates that a maternal continuous intravenous fluorouracil infusion at a dose of 200 mg/square meter daily produces u
Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy. To compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100). Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021. Patients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years. The primary end point was overall survival time from randomization. Of the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (<0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P = .009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [
To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group (P < .001). Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.