title: Risk of Gastrointestinal Events During Lapatinib Therapy: A Meta-Analysis From 12,402 Patients With Cancer.
abstract: Lapatinib, a tyrosine kinase inhibitor used as an anticancer therapeutic agent, has adverse events associated with treatment resulting in noncompliance and withdrawal from the therapy. Here, we performed meta-analysis of published clinical trials to determine relative risk (RR) and incidence of gastrointestinal events during lapatinib therapy in patients with cancer. A comprehensive literature search was performed and summary incidence, RR, and 95% confidence intervals (CI) were calculated using fixed-effects or random-effects models, depending on the heterogeneity of trials. Thirty-six trials with 12,402 patients were included; summary incidences of all-grade gastrointestinal events in patients with cancer were diarrhea 57.8%, nausea 30.8%, and vomiting 19.6%. Lapatinib combination with chemotherapy or any anti-HER2 mAbs were associated with significant risk of all-grade diarrhea [(RR 3.64, 95% CI, 2.96-4.49), (RR 2.89, 95% CI, 2.21-3.79), respectively] and high-grade diarrhea [(RR 11.25, 95% CI, 7.31-17.33), (RR 9.96, 95% CI, 7.23-13.72), respectively], and lapatinib combination with chemotherapy group showed a significantly increased risk of all-grade nausea (RR 1.54, 95% CI, 1.25-1.89). Lapatinib combination with chemotherapy or any anti-HER2 mAbs were associated with significant risk of all-grade vomiting [(RR 1.47, 95% CI, 1.12-1.93), (RR 1.30, 95% CI, 1.11-1.52), respectively]. Lapatinib combination with any anti-HER2 mAbs was associated with a significant risk of high-grade vomiting (RR 2.25, 95% CI, 1.41-3.61). This study revealed a significantly increased risk of diarrhea, nausea, and vomiting in patients with cancer receiving lapatinib, suggesting that appropriate clinical intervention and gastrointestianal protective agents should be emphasized.
authors.affiliation: Medical College of Nanchang University, Nanchang, China.
authors.forename: XiongWen
authors.initials: X
authors.lastname: Yang
authors.affiliation: Medical College of Nanchang University, Nanchang, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Xiaoshu
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Thoracic Surgery, Jiangxi Province Tumor Hospital, Nanchang, China.
authors.forename: YuKang
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: YingZhang
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D000077341:Lapatinib; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011799:Quinazolines / Q000009:adverse effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human