title: A Phase II Study of Intermittent Sunitinib in Previously Untreated Patients With Metastatic Renal Cell Carcinoma.
abstract: Purpose Sunitinib is a standard initial therapy in metastatic renal cell carcinoma (mRCC), but chronic dosing requires balancing toxicity with clinical benefit. The feasibility and clinical outcome with intermittent sunitinib dosing in patients with mRCC was explored. Patients and Methods Patients with treatment-naïve, clear cell mRCC were treated with four cycles of sunitinib (50 mg once per day, 4 weeks of receiving treatment followed by 2 weeks of no treatment). Patients with a ≥ 10% reduction in tumor burden (TB) after four cycles had sunitinib held, with restaging scans performed every two cycles. Sunitinib was reinitiated for two cycles in those patients with an increase in TB by ≥ 10%, and again held with ≥ 10% TB reduction. This intermittent sunitinib dosing continued until Response Evaluation Criteria in Solid Tumors-defined disease progression while receiving sunitinib, or unacceptable toxicity occurred. The primary objective was feasibility, defined as the proportion of eligible patients who underwent intermittent therapy. Results Of 37 patients enrolled, 20 were eligible for intermittent therapy and all patients (100%) entered the intermittent phase. Patients were not eligible for intermittent sunitinib because of progressive disease (n = 13), toxicity (n = 1), or consent withdrawal (n = 3) before the end of cycle 4. The objective response rate was 46% after the first four cycles of therapy. The median increase in TB during the periods off sunitinib was 1.6 cm (range, -2.9 to 3.4 cm) compared with the TB immediately before stopping sunitinib. Most patients exhibited a stable sawtooth pattern of TB reduction while receiving sunitinib and TB increase while not receiving sunitinib. Median progression-free survival to date is 22.4 months (95% CI, 5.4 to 37.6 months) and median overall survival is 34.8 months (95% CI, 14.8 months to not applicable). Conclusion Periodic extended sunitinib treatment breaks are feasible and clinical efficacy does not seem to be compromised.
authors.affiliation: All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Moshe C
authors.initials: MC
authors.lastname: Ornstein
authors.affiliation: All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Wood
authors.affiliation: All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.affiliation: All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Allman
authors.affiliation: All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Beach
authors.affiliation: All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Allison
authors.initials: A
authors.lastname: Martin
authors.affiliation: All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Beth R
authors.initials: BR
authors.lastname: Zanick
authors.affiliation: All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Petros
authors.initials: P
authors.lastname: Grivas
authors.affiliation: All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Tim
authors.initials: T
authors.lastname: Gilligan
authors.affiliation: All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Garcia
authors.affiliation: All authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib