Development and validation of a prediction index for hand-foot skin reaction in cancer patients receiving sorafenib.
BACKGROUND
This study describes a repeated measures prediction index to identify patients at high risk of ≥grade 2 hand-foot skin reaction (HFSR) before each week of sorafenib therapy.


METHODS
Data from 451 patients who received a sorafenib (400 mg bid) as part of a clinical trial were reviewed (Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356: 125-134). Generalized estimating equations were used to develop the final risk model. A risk-scoring algorithm (range 0-58) was then derived from the final model coefficients. External validation was then carried out on a new sample of 1145 patients who received sorafenib under an expanded access program.


RESULTS
Pretreatment white blood cell count, female gender, good performance status, presence of lung and liver metastases and number of affected organs were predictors for ≥grade 2 HFSR. A nonlinear association between HFSR risk and treatment duration was also identified where risk was maximized at week 5 followed by a gradual decline. Before each week of therapy, patients with risk scores>40 would be considered at high risk for developing ≥grade 2 HFSR.


CONCLUSIONS
The application and planned continued refinement of this prediction tool will be an important source of patient-specific risk information for the development of moderate to severe HFSR.
Caduceus Information Systems Inc., Toronto. Electronic address: george.dranitsaris@gmail.com.
G
G
Dranitsaris
Department of Medical Oncology, London Regional Cancer Program, London, Canada.
M D
MD
Vincent
Global Medical Affairs and Statistics, Bayer HealthCare Pharmaceuticals, Montville.
J
J
Yu
Global Medical Affairs and Statistics, Bayer HealthCare Pharmaceuticals, Montville.
L
L
Huang
Global Medical Affairs and Statistics, Bayer HealthCare Pharmaceuticals, Montville.
F
F
Fang
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA.
M E
ME
Lacouture
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D060831:Hand-Foot Syndrome / Q000175:diagnosis / Q000209:etiology*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011237:Predictive Value of Tests; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D015203:Reproducibility of Results; D012307:Risk Factors; D000077157:Sorafenib; D055815:Young Adult
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib