title: Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer.
abstract: Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme. ECOG performance status >1, histology other than clear cell and presence of brain metastases were no exclusion criteria. Eighty-two patients were treated: 23% reached a partial response, 50% had stable disease, 20% progressed and six patients were not evaluable. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 15 months. Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both. Stomatitis, fatigue, hand-foot syndrome and a combination of grade 1-2 adverse events were the most frequent reasons for dose reduction. In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender. On the basis of age and gender, a model was developed that could predict the probability of severe toxicity.
authors.affiliation: Department of Medical Oncology, VU University medical center, Amsterdam, The Netherlands.
authors.forename: A A M
authors.initials: AA
authors.lastname: van der Veldt
authors.forename: E
authors.initials: E
authors.lastname: Boven
authors.forename: H H
authors.initials: HH
authors.lastname: Helgason
authors.forename: M
authors.initials: M
authors.lastname: van Wouwe
authors.forename: J
authors.initials: J
authors.lastname: Berkhof
authors.forename: G
authors.initials: G
authors.lastname: de Gast
authors.forename: H
authors.initials: H
authors.lastname: Mallo
authors.forename: C N
authors.initials: CN
authors.lastname: Tillier
authors.forename: A J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: J B A G
authors.initials: JB
authors.lastname: Haanen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects* / Q000627:therapeutic use*; D012307:Risk Factors; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib