Capecitabine and Palmar-plantar erythrodysaesthesia (hand-foot syndrome): is the FAERS signal real?
Capecitabine ↔ Palmar-plantar erythrodysaesthesia (hand-foot syndrome)
Reporting over time (stimulated-reporting check)
No reporting spike: the pair's share of the drug's reports is fairly stable over time (busiest two years hold 19% of 6,537 reports), so stimulated reporting is unlikely to explain the signal.
Bars: reports per year as a share of all FAERS reports for this drug, 2004–2025; amber = spike year (>3× the median share, ≥50 reports). Source: openFDA count=receivedate, retrieved 2026-10-09.
Capecitabine is an oral fluoropyrimidine used for colorectal and breast cancer, and palmar-plantar erythrodysesthesia — "hand-foot syndrome": painful redness, swelling, and peeling of the palms and soles — is its signature toxicity. It occurs in a substantial minority of treated patients, is clearly dose- and schedule-dependent, and is well characterized and manageable (dose reduction, interruption, emollients, pyridoxine). This is a mechanistically direct, expected effect of the drug's own pharmacology, not an idiosyncratic reaction.
Regulatory basis: capecitabine prescribing information (hand-foot syndrome listed among the most common adverse reactions); confirmed by a randomized comparator arm (§ trial data below). A class effect of the fluoropyrimidines.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Appears during cycles of treatment, after exposure begins |
| Strength | met | PRR 92, and ~20%+ incidence in a randomized comparator arm |
| Consistency | met | Reproduced across capecitabine trials and real-world cohorts |
| Specificity | met | Highly characteristic of the fluoropyrimidine class |
| Biological gradient | met | Striking dose/schedule dependence; continuous infusion and higher doses raise risk |
| Plausibility | met | Direct toxicity in high-turnover acral skin; named mechanism |
| Coherence | met | Coheres with the drug's cytotoxicity and with other fluoropyrimidines |
| Experiment | met | Resolves with dose reduction or interruption — a clean dechallenge |
| Analogy | met | Seen with 5-fluorouracil and other fluoropyrimidines |
This page's own qualitative read, not an automated/citation-gated assessment.
✓ Trial evidence found — physician's-choice chemotherapy (incl. capecitabine) vs talazoparib in BRCA breast cancer (NCT01945775, EMBRACA)
| Term (as recorded) | Physician's-choice arm (n=126) | Talazoparib arm (n=286) |
|---|---|---|
| Palmar-plantar erythrodysaesthesia syndrome (other events) | 28 | 4 |
Hand-foot syndrome appeared in 28/126 (~22%) of the comparator arm, which includes capecitabine, versus 4/286 (~1.4%) on talazoparib — a large, textbook-consistent difference. Caveat: the comparator arm pools several drugs (capecitabine, eribulin, gemcitabine, vinorelbine), so it confirms the class/regimen effect more than capecitabine alone. View on ClinicalTrials.gov →