Capecitabine-associated hand–foot–skin reaction is an independent clinical predictor of improved survival in patients with colorectal cancer

• Published in: British journal of cancer 2012-11, Vol.107 (10), p.1678-1683
• Main Authors: Hofheinz, R-D, Heinemann, V, von Weikersthal, L F, Laubender, R P, Gencer, D, Burkholder, I, Hochhaus, A, Stintzing, S
• Format: Article
• Language: English
• Subjects: 692/699/1503/1504/1885; 692/699/67/322; 692/700/1750/1976; 692/700/565/2194; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Cancer therapies; Capecitabine; Clinical Study; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Disease-Free Survival; Drug Resistance; Epidemiology; Female; Fluorouracil - adverse effects; Fluorouracil - analogs & derivatives; Fluorouracil - therapeutic use; Gastroenterology. Liver. Pancreas. Abdomen; Hand-Foot Syndrome - etiology; Hand-Foot Syndrome - pathology; Hematology; Humans; Kaplan-Meier Estimate; Male; Medical research; Medical sciences; Metastasis; Middle Aged; Molecular Medicine; Oncology; Patients; Prospective Studies; Rectal Neoplasms - drug therapy; Rectal Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Toxicity; Treatment Outcome; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.434

Background: Hand–foot–skin reaction (HFSR) is an adverse event frequently observed during treatment with capecitabine (cape). In the present analysis, we sought to evaluate the potential association of HFSR and survival in German patients with metastatic colorectal cancer and locally advanced rectal cancer treated with cape in clinical trials. Methods: Patients of the Arbeitsgemeinschaft für Internistische Onkologie (AIO) KRK-0104 and the Mannheim rectal cancer trial were evaluated. HFSR was graded according to NCI-CTC criteria in both trials. Time to first occurrence of HFSR was described per cycle and HFSR developing during cycles 1 and 2 was defined as ‘early HFSR’. Baseline characteristics between the patient groups with or without HFSR were compared using Mann–Whitney- U , Fisher’s exact or χ 2 -test, as appropriate. Haematological and non-haematological toxicities observed in both groups were compared using Fisher’s exact test. Progression-free (PFS) or disease-free (DFS) as well as overall survival (OS) data from both trials were pooled and the HFSR group was compared with the non-HFSR using Kaplan–Meier analysis. Results: A total of 374 patients were included, of whom 29.3% developed any HFSR. Of these, 51% had early HFSR. Baseline characteristics were comparable between both HFSR groups concerning age, gender, ECOG performance status and UICC stage. On multivariate analysis none of these factors had influence on the occurrence of HFSR. The percentage of all-grade (and grade 3–4) haematological toxicities did not differ between both the groups. By contrast, patients exhibiting HFSR had a significantly higher rate of all-grade (but not grade 3–4) diarrhoea, stomatitis/mucositis and fatigue ( P