Management of hand-foot syndrome in patients treated with ...

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S36 cycle. An example would be increasing the interval between cycles to 2 weeks or changing the cycle length (e.g. 10 days on, 11 days off). ARTICLE IN PRESS Table 3 Capecitabine dose-modification scheme for all adverse events. NCI-CTC toxicity grade Maintain interruption Appearance of toxicity Adjustment during therapy Adjustment for next cycle (relative to initial dose) 2 1st Interrupt until resolved to grade 0/1 100% 2nd Interrupt until resolved to grade 0/1 75% 3rd Interrupt until resolved to grade 0/1 50% 4th Discontinue drug permanently 3 1st Interrupt until resolved to grade 0/1 75% 2nd Interrupt until resolved to grade 0/1 50% 3rd Discontinue drug permanently 4 a 1st Discontinue drug permanently or interrupt until resolved to grade 0/1 b 50% NCI-CTC, National Cancer Institute Common Toxicity Criteria. a Not applicable to HFS. b At discretion of the clinician. NO 55-year old woman with MCRC Initiate treatment with oral capecitabine (1250 mg/m 2 twice daily on days 1–14, every 3 weeks) 1st episode of grade 2 HFS Interrupt capecitabine treatment Does HFS resolve to grade 0/1? YES Reintroduce capecitabine at 1250 mg/m twice daily Discontinue drug permanently OR Interrupt until resolved to grade 0/1 (at the discretion of the clinician) 1st episode of grade 4 HFS OR 3rd episode of grade 3 HFS Maintain interruption Maintain interruption 1st episode of grade 3 HFS OR 2nd episode of grade 2 HFS NO Interrupt capecitabine treatment Does HFS resolve to grade 0/1? YES Reintroduce capecitabine at 1000 mg/m twice daily 2nd episode of grade 3 HFS OR 3rd episode of grade 2 HFS NO Interrupt capecitabine treatment Does HFS resolve to grade 0/1? YES Reintroduce capecitabine at 625 mg/m twice daily Y. Lassere, P. Hoff Figure 2 Example of managing a patient with MCRC who develops HFS during treatment with capecitabine single-agent therapy. When the guidelines for dose interruption and dose reduction are followed, hospitalisations are rare. In a recently presented study of capecitabine
vs. 5-FU/LV (Mayo Regimen) as adjuvant therapy for patients with Dukes’ C colon cancer, only two capecitabine-treated patients required hospitalisation (for 1 day) (Cassidy et al., 2004b; Scheithauer et al., 2003). Supportive measures There are few supportive measures that have proven effectiveness in controlling symptoms. Use of topical emollients and creams would appear to be a prudent prophylactic and symptomatic treatment at the first signs of grade 1 HFS (Gerbrecht, 2003). Regular use of a topical petroleum-lanolin based ointment with antiseptic hydroxyquinoline sulphate applied 3-times daily has been reported to alleviate the symptoms of HFS induced by various chemotherapeutic agents (including capecitabine) (Chin et al., 2001). It should be noted that, anecdotally, some people are allergic to lanolinbased products. Nevertheless, dose interruption and, if necessary, dose reduction should remain the primary tool in HFS management. As a general recommendation, symptoms can often be relieved by: immersing the hands and feet in cool water avoiding extremes of temperature, pressure, and friction on the skin cushioning sore skin with soft pads topical wound care and consultation with a dermatologist for any blistering or ulceration (Gerbrecht, 2003). Topical (Esteve et al., 1995; Gordon et al., 1995; Komamura et al., 1995; Vakalis et al., 1998; Vukelja et al., 1989) or systemic (Brown et al., 1991; Esteve et al., 1995; Hellier et al., 1996; Hoff et al., 1998; Titgan, 1997) corticosteroids have been reported to be useful for prophylaxis and treatment of HFS induced by a range of different drugs, although their use in capecitabine-associated HFS is unproven. While steroids are capable of reducing inflammation, their long-term use can lead to thinning of the skin, which is likely to cause more symptoms. Diemethysulfoxide 99% 4-times daily has been reported to be of benefit in patients receiving liposomal doxorubicin (Lopez et al., 1999) but is again unproven with capecitabineinduced HFS. The use of pyridoxine (vitamin B6), at a highly variable dose, has been anecdotally reported to be useful for prophylaxis and treatment of HFS induced by various agents, e.g. capecitabine, 5- FU, docetaxel (Andres et al., 2003; Beveridge et al., 1990; Fabian et al., 1990; Lauman and Mortimer, 2001; Van Cutsem et al., 2000; Vukelja ARTICLE IN PRESS Management of hand-foot syndrome S37 et al., 1989, 1993). One study in dogs showed that prophylactic pyridoxine significantly delayed the onset and severity of HFS induced by liposomal pegylated doxorubicin, allowing a higher cumulative dose to be delivered (Vail et al., 1998). As pyridoxine is a safe nutritional supplement, its prophylactic use might appear appealing, although efficacy needs to be proven prospectively in controlled trials before routine treatment can be recommended. Such studies need to confirm no effect on capecitabine efficacy and whether effective prophylaxis might permit administration of a higher cumulative dose of capecitabine. An interesting adjunctive treatment with capecitabine might be concurrent use of celecoxib, a COX-2 antagonist used incidentally for control of pain and arthritis. In a retrospective series of 67 patients receiving capecitabine, the addition of celecoxib appeared to reduce the rate of HFS4grade 1 (from 34% with capecitabine alone to 13% with capecitabine plus celecoxib), as well as diarrhoea4grade 2 (from 29% to 3%) (Lin et al., 2002). However, in this series, most patients required dose reductions. This retrospective study has generated a hypothesis that needs to be tested in a prospective randomised setting. Until then, there is insufficient evidence to recommend the use of celecoxib in the prophylaxis of HFS. Conclusions While HFS is a common and inconvenient side effect with capecitabine, the condition is easily managed with dose interruption and, if necessary, dose reductions. Prompt intervention means that patients do not need to interrupt treatment for long periods and can, therefore, continue to benefit from capecitabine therapy. Oncology nurses, through patient education and close clinical assessment, play a crucial role in the early identification and prevention of progressive pain, loss of the skin’s integrity, and disability. In addition, once HFS is identified, the nurses’ role in patient education, support, and symptom management is essential to maintain effective patient care and, in some cases, the patient’s willingness to continue therapy. Table 4 summarises some of the key preventative and management techniques for HFS. Patient education needs to highlight the need for reporting side effects and interrupting therapy when required. Written materials should be provided for the patient to reinforce the teaching
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