Placebo-controlled trial to determine the effectiveness of a urea/lactic acid-based topical keratolytic agent for prevention of capecitabine-induced hand-foot syndrome: North Central Cancer Treatment Group Study N05C5.
OBJECTIVE
Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine for which no effective preventative treatment has been definitively demonstrated. This trial was conducted on the basis of preliminary data that a urea/lactic acid-based topical keratolytic agent (ULABTKA) may prevent HFS.


METHODS
A randomized, double-blind phase III trial evaluated 137 patients receiving their first ever cycle of capecitabine at a dose of either 2,000 or 2,500 mg/m(2) per day for 14 days. Patients were randomly assigned to a ULABTKA versus a placebo cream, which was applied to the hands and feet twice per day for 21 days after the start of capecitabine. Patients completed an HFS diary (HFSD) daily. HFS toxicity grade (Common Terminology Criteria for Adverse Events [CTCAE] v3.0) was also collected at baseline and at the end of each cycle. The primary end point was the incidence of moderate/severe HFS symptoms in the first treatment cycle, based on the patient-reported HFSD.


RESULTS
The percentage of patients with moderate/severe HFS symptoms was not different between groups, being 13.6% in the ULABTKA arm and 10.2% in the placebo arm (P = .768 by Fisher's exact test). The odds ratio was 1.37 (95% CI, 0.37 to 5.76). Cycle 1 CTCAE skin toxicity was higher in the ULABTKA arm but not significantly so (33% v 27%; P = .82). No significant differences were observed in other toxicities between groups.


CONCLUSIONS
These data do not support the efficacy of a ULABTKA cream for preventing HFS symptoms in patients receiving capecitabine.
Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Sherry L
SL
Wolf
Rui
R
Qin
Smitha P
SP
Menon
Kendrith M
KM
Rowland
Sachdev
S
Thomas
Robert
R
Delaune
Diana
D
Christian
Eduardo R
ER
Pajon
Daniel V
DV
Satele
Jeffrey L
JL
Berenberg
Charles L
CL
Loprinzi
D000287:Administration, Topical; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects; D000069287:Capecitabine; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives; D005533:Foot Dermatoses / Q000139:chemically induced / Q000517:prevention & control*; D006229:Hand Dermatoses / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D007641:Keratolytic Agents / Q000627:therapeutic use*; D019344:Lactic Acid / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D013577:Syndrome; D014508:Urea / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D007641:Keratolytic Agents; D003841:Deoxycytidine; D019344:Lactic Acid; D000069287:Capecitabine; D014508:Urea; D005472:Fluorouracil