capecitabine
Regulatory sources consulted
Approved indications
- Adjuvant treatment of stage III colon cancer; metastatic colorectal cancer; first-line treatment of advanced gastric cancer with platinum; and locally advanced or metastatic breast cancer with docetaxel after failure of anthracycline-containing chemotherapy, or as monotherapy after failure of a taxane and anthracycline or when further anthracycline is unsuitable.
Contraindications
Absolute
- Hypersensitivity to capecitabine, fluorouracil, or excipients, or a history of a severe unexpected reaction to fluoropyrimidines.
- Complete DPD deficiency; pregnancy or breastfeeding; severe leukopenia, neutropenia, or thrombocytopenia; severe hepatic impairment; CrCl <30 mL/min; recent or concomitant brivudine.
Clinical warnings
- Perform DPYD genetic testing before treatment unless therapy is needed immediately. Avoid capecitabine in complete DPD deficiency; in partial deficiency individualize according to tolerability and treatment intent, without a fixed percentage. — OpenFDA, set_id 007e3432-c8aa-2a76-52ba-c346924c08a7
- Monitor blood counts before each cycle and through the nadir. Delay or modify the cycle for myelosuppression; infections and bleeding may be severe or fatal. — CIMA/AEMPS, ficha técnica 84871
- Overdose requires urgent assessment: administer uridine triacetate within 96 hours after the end of fluoropyrimidine administration. — DailyMed, capecitabine tablets
Drug interactions
- ModerateBrivudine
Mechanism: DPD inhibition may cause fatal fluoropyrimidine toxicity.
Recommendation: Allow at least 4 weeks between brivudine and capecitabine. Brivudine may be started 24 hours after the last capecitabine dose.
CIMA/AEMPS, ficha técnica 84871
- HighCoumarin anticoagulants
Mechanism: Capecitabine may markedly and belatedly increase INR and bleeding risk.
Recommendation: Monitor INR frequently during treatment and after completion; adjust the anticoagulant.
CIMA/AEMPS, ficha técnica 84871
- HighPhenytoin
Mechanism: Capecitabine may increase phenytoin concentrations.
Recommendation: Monitor concentrations and toxicity and adjust phenytoin if needed.
CIMA/AEMPS, ficha técnica 84871
- HighFolinic acid or folic acid
Mechanism: They may increase capecitabine toxicity.
Recommendation: Use only within a defined protocol and intensify toxicity monitoring.
CIMA/AEMPS, ficha técnica 84871
- HighAllopurinol
Mechanism: It may reduce capecitabine efficacy.
Recommendation: Avoid concomitant administration.
CIMA/AEMPS, ficha técnica 84871
Pregnancy and lactation
It is contraindicated during pregnancy and breastfeeding. Perform pregnancy testing before treatment. Women must use effective contraception during treatment and for 6 months afterward; men during treatment and for 3 months afterward. Do not breastfeed during treatment or for 1 week afterward.
Recent literature (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.