capecitabine
Sources réglementaires consultées
Indications approuvées
- Traitement adjuvant du cancer du côlon de stade III ; cancer colorectal métastatique ; première ligne du cancer gastrique avancé avec un sel de platine ; et cancer du sein localement avancé ou métastatique avec docétaxel après échec d’une chimiothérapie contenant une anthracycline, ou en monothérapie après échec d’un taxane et d’une anthracycline ou si une anthracycline supplémentaire ne convient pas.
Contre-indications
Absolues
- Hypersensibilité à la capécitabine, au fluorouracile ou aux excipients, ou antécédent de réaction sévère et inattendue aux fluoropyrimidines.
- Déficit complet en DPD ; grossesse ou allaitement ; leucopénie, neutropénie ou thrombocytopénie sévère ; insuffisance hépatique sévère ; ClCr <30 ml/min ; brivudine récente ou concomitante.
Mises en garde cliniques
- Réaliser un test génétique DPYD avant le traitement sauf nécessité immédiate. Éviter la capécitabine en cas de déficit complet en DPD ; en cas de déficit partiel, individualiser selon la tolérance et l’intention thérapeutique, sans pourcentage fixe. — OpenFDA, set_id 007e3432-c8aa-2a76-52ba-c346924c08a7
- Surveiller la numération avant chaque cycle et pendant le nadir. Différer ou modifier le cycle en cas de myélosuppression ; les infections et hémorragies peuvent être graves ou mortelles. — CIMA/AEMPS, ficha técnica 84871
- Un surdosage exige une évaluation urgente : administrer le triacétate d’uridine dans les 96 heures suivant la fin de l’administration de la fluoropyrimidine. — DailyMed, capecitabine tablets
Interactions médicamenteuses
- ModéréeBrivudine
Mécanisme: L’inhibition de la DPD peut provoquer une toxicité fluoropyrimidinique mortelle.
Recommandation: Respecter au moins 4 semaines entre brivudine et capécitabine. La brivudine peut être débutée 24 heures après la dernière dose de capécitabine.
CIMA/AEMPS, ficha técnica 84871
- SévèreAnticoagulants coumariniques
Mécanisme: La capécitabine peut augmenter fortement et tardivement l’INR et le risque hémorragique.
Recommandation: Surveiller fréquemment l’INR pendant et après le traitement ; ajuster l’anticoagulant.
CIMA/AEMPS, ficha técnica 84871
- SévèrePhénytoïne
Mécanisme: La capécitabine peut augmenter les concentrations de phénytoïne.
Recommandation: Surveiller concentrations et toxicité et ajuster la phénytoïne si nécessaire.
CIMA/AEMPS, ficha técnica 84871
- SévèreAcide folinique ou acide folique
Mécanisme: Ils peuvent augmenter la toxicité de la capécitabine.
Recommandation: Utiliser uniquement dans un protocole défini et renforcer la surveillance de la toxicité.
CIMA/AEMPS, ficha técnica 84871
- SévèreAllopurinol
Mécanisme: Peut réduire l’efficacité de la capécitabine.
Recommandation: Éviter l’administration concomitante.
CIMA/AEMPS, ficha técnica 84871
Grossesse et allaitement
Elle est contre-indiquée pendant la grossesse et l’allaitement. Réaliser un test de grossesse avant le traitement. Les femmes doivent utiliser une contraception efficace pendant le traitement et pendant 6 mois après ; les hommes pendant le traitement et pendant 3 mois après. Ne pas allaiter pendant le traitement ni pendant 1 semaine après.
Bibliographie récente (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.