Capecitabine-induced Toxicity: An Outcome Study into Drug Safety

Abstract

Background: The use of capecitabine has risen exponentially in the Netherlands since 2001. Clinical trials describe a mild toxicity profile. Because circumstances in daily clinical practice can differ a lot from clinical trial setting, we performed this retrospective analysis in a large community hospital to verify toxicity in a clinical situation. Methods: A retrospective cohort study was conducted in patients with malignancies of the gastrointestinal tract or breast treated with capecitabine in the period of January 2007 to January 2009. Primary study endpoint was the incidence and severity of capecitabine-induced toxicity in daily clinical practice. Secondary endpoint concerned determination of risk factors for toxicity due to capecitabine. Results: Of 281 patients 92% experienced some degree of toxicity. Grade 3-4 toxicity occurred in 30% of patients receiving monotherapy and in 47% with combination therapy. This was in accordance with the literature. Type of toxicity varied, but gastro intestinal symptoms and hand foot syndrome were most commonly found. Risk of toxicity increased with increasing age, independently of creatinine clearance. Conclusions: Therapy with capecitabine monotherapy or capecitabine containing regiments in daily clinical practice is accompanied by considerable toxicity, but frequency and severity are consistent with published clinical trials. More toxicity can be expected with increasing age.

Synthesis of Thiol Derivatives of Biological Active Compounds for Nanotechnology Application

“…The compounds 1 – 9 mentioned above were selected for our studies with respect to important criteria; first of all, their known biological activities. Secondly, some of them have unsatisfactory properties limiting their use as drugs, i.e., bioavailability [ 23 ], water solubility [ 27 ], and high toxicity which eventually limit their therapeutic window [ 28 ]. These parameters could be improved by incorporation of a thiol linker into their structures, which might also serve an opportunity for the future synthesis of gold nanoparticles (AuNPs) via S-Au covalent bonds.…”

Evaluation of Correlation Between Serum Level of Dihydropyrimidine Dehydrogenase Enzyme and Capecitabine Induced Adverse Reaction

“…It can be used as monotherapy or in combination with other drugs such as oxaliplatin, irinotecan and cisplatin in GI cancer, and monoclonal antibodies such as trastuzumab (Herceptin®) or bevacizumab (Avastin®) in breast cancer (1). Capecitabine is a relatively safe option in comparison with several other chemotherapy regimens.…”

“…A familial state caused by an allelic mutation in the DPYD gene can lead to "DPD deficiency syndrome". The Partial and complete DPD deficiency are reported in 3% -5% and 0.2% of population, respectively (1,4). So far 39 different mutations are recognized in the DPD gene (5).…”

Topical Silymarin Administration for Prevention of Capecitabine‐Induced Hand–Foot Syndrome: A Randomized, Double‐Blinded, Placebo‐Controlled Clinical Trial

“…It generates 5-FU selectively in tumor site to prevent systemic drug exposure. It is widely used as monotherapy or in combination with other agents in gastrointestinal cancers (Lassere and Hoff, 2004;Gressett et al, 2006;Azuma et al, 2012;Baan et al, 2014;Murugan et al, 2016).…”

“…Capecitabine is generally well tolerated. Diarrhea, stomatitis, hand–foot syndrome (HFS), and fatigue are its most common adverse reactions (Baan et al , ). The dose limiting side effect of capecitabine is HFS which is reported in more than 50% of the patients.…”