Lanolin-based dexpanthenol cream, topical hydrocortisone or observation in the prevention of capecitabine-induced hand-foot syndrome: a phase III trial

ABSTRACT

Introduction: The use of capecitabine is associated with hand-foot syndrome (HFS). Since there is anecdotal evidence that lanolin-based creams and topical steroids are useful for the treatment of HFS, we conducted a three- arm phase III trial to compare observation, lanolin-based cream with dexpanthenol (L-D), and topical hydrocortisone in the prevention of HFS.

Material and Methods: Patients with breast or colorectal cancer with indication to use capecitabine as a single agent or in combination were randomized in an open-label fashion to one of the three arms. The initial capecitabine dose was 1,000 or 1,250mg/m², according to the physicians discretion and clinical practice, and dose adjustments followed the local label. The primary endpoint was the frequency of HFS of any grade in the intent-to-treat population, whereas quality of life (QoL), change from baseline in performance status and adverse events were secondary endpoints.

Results: Mean age among the 595 patients randomized was 58 years, and 69% were women. 37% of patients had advanced breast cancer and 63% of patients had colorectal cancer. Capecitabine was used as a single agent in 67% of patients; among the remaining 33% of patients, 82% were treated with oxaliplatin-based combinations. HFS of any grade was seen in 35.6% of patients in the observation group, 24.9% with L-D, and 34.3% with hydrocortisone (p=0.039). The unadjusted odds ratio for the frequency of HFS in the arm treated with L-D was 0.60 (95%CI, 0.39 to 0.92). Only between 2.6% and 9.4% of patients had grade 3 HFS. There were no statistically significant differences in mean change from baseline in any of the QoL scores, the distribution of performance status, or the frequency of adverse events among the three arms.

Conclusion: L-D could be considered a standard strategy in the attempt to prevent capecitabine-induced HFS.

RESUMO

Introdução: O uso de capecitabina está associado à síndrome mão-pé (SMP). Como há poucas evidências sobre a eficácia de cremes à base de lanolina e esteroides tópicos no tratamento da SMP, realizamos um estudo de fase III de três braços para comparar observação, creme à base de lanolina com dexpantenol (L-D) e hidrocortisona tópica na prevenção de SMP.

Material e Métodos: Pacientes com câncer de mama ou colorretal com indicação de uso de capecitabina como agente único ou em combinação foram randomizados de forma aberta para um dos três braços. A dose inicial de capecitabina foi de 1.000 ou 1.250mg/m², conforme critério médico e prática clínica, e os ajustes de dose seguiram a bula local. O endpoint primário foi a frequência de SMP de qualquer grau na população com intenção de tratamento, enquanto a qualidade de vida (QoL), mudanças em performance status em relação ao início do estudo e eventos adversos foram endpoints secundários.

Resultados: A média de idade entre os 595 pacientes randomizados foi de 58 anos, e 69% eram mulheres. 37% dos pacientes tinham câncer de mama avançado, e 63% dos pacientes tinham câncer colorretal. A capecitabina foi usada como agente único em 67% dos pacientes; entre os 33% restantes, 82% foram tratados com combinações à base de oxaliplatina. SMP de qualquer grau foi observada em 35,6% dos pacientes do grupo de observação, 24,9% com L-D e 34,3% com hidrocortisona (p=0,039). A razão de chances (não ajustada) para a frequência de SMP no braço tratado com L-D foi de 0,60 (IC95%, 0,39 a 0,92). Apenas entre 2,6% e 9,4% dos pacientes tiveram SMP de grau 3. Não foram encontradas diferenças estatisticamente significativas na mudança média de nenhum dos escores de QoL em relação ao início do estudo, na distribuição do performance status ou na frequência de eventos adversos entre os três braços.

Conclusão: A L-D pode ser considerada uma estratégia padrão na tentativa de prevenir a SMP induzida pela capecitabina.

Keywords:

Breast neoplasms - Capecitabine - Colorectal neoplasms - Glucocorticoids - Hand-foot syndrome - Dexpanthenol

Descritores:

Neoplasias mamárias - Capecitabina - Neoplasias colorretais - Glicocorticóides - Síndrome mão-pé - Dexpantenol

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