title: Clinical outcomes for patients with metastatic renal cell carcinoma treated with alternative sunitinib schedules.
abstract: OBJECTIVE
  We identified sunitinib alternative schedules that maintained dose intensity while decreasing adverse events in patients with metastatic renal cell cancer. We also determined the impact of alternative schedules on clinical outcomes.
  
  
  METHODS
  We retrospectively reviewed the records of patients 18 years old or older with clear cell metastatic renal cell cancer who received first line sunitinib between January 26, 2006 and March 1, 2011 at our major comprehensive cancer center. A subset of patients was switched at the first intolerable adverse event from the traditional schedule of 28 days on and 14 days off to a schedule of 14 days on and 7 days off or other alternative schedules. A control group underwent standard dose reduction. We estimated progression-free and overall survival by the Kaplan-Meier method. Predictors of progression-free and overall survival were analyzed using Cox regression.
  
  
  RESULTS
  A total of 187 patients were included in analysis, of whom 87% were on the traditional schedule at baseline. During treatment 53% of patients continued on the traditional schedule and 47% began or were transitioned to alternative schedules. Baseline characteristics were similar. Adverse events prompting schedule modification included fatigue in 64% of cases, hand-foot syndrome in 38% and diarrhea in 32%. Median time to alternative schedules was 5.6 months. Median overall survival was 17.7 months (95% CI 10.8-22.2) on the traditional schedule compared to 33.0 months (95% CI 29.3-not estimable) on alternative schedules (p <0.0001). On multivariable analysis poor Eastern Cooperative Oncology Group (ECOG) performance status, increased lactate dehydrogenase, decreased albumin, unfavorable Heng criteria and the traditional schedule were associated with decreased overall survival (p <0.05).
  
  
  CONCLUSIONS
  Sunitinib administered on alternative schedules may mitigate adverse events while achieving outcomes comparable to those of the traditional schedule in patients with metastatic renal cell cancer. Prospective investigations of alternate dosing schemas are warranted.
authors.affiliation: Department of Pharmacy Clinical Programs, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Atkinson
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Sarathi
authors.initials: S
authors.lastname: Kalra
authors.affiliation: Division of Quantitative Sciences, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Radiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Tharakeswara
authors.initials: T
authors.lastname: Bathala
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Paul
authors.initials: P
authors.lastname: Corn
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address: ejonasch@mdanderson.org.
authors.forename: Eric
authors.initials: E
authors.lastname: Jonasch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077210:Sunitinib; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: carcinoma; drug administration schedule; drug-related side effects and adverse reactions; kidney; renal cell; sunitinib
references.citation: Eur J Cancer. 2009 Jan;45(2):228-47
references.pmid: 19097774
references.citation: Ann Oncol. 2012 Dec;23(12):3137-3143
references.pmid: 22700990
references.citation: J Clin Oncol. 2010 Feb 20;28(6):1061-8
references.pmid: 20100962
references.citation: Lancet. 2007 Dec 22;370(9605):2103-11
references.pmid: 18156031
references.citation: Lancet Oncol. 2009 Aug;10(8):757-63
references.pmid: 19615940
references.citation: J Natl Cancer Inst. 2011 May 4;103(9):763-73
references.pmid: 21527770
references.citation: J Clin Oncol. 2009 Mar 10;27(8):1280-9
references.pmid: 19171708
references.citation: Cancer. 2011 Feb 1;117(3):534-44
references.pmid: 20845482
references.citation: Ann Oncol. 2007 Jul;18 Suppl 9:ix90-3
references.pmid: 17631603
references.citation: J Clin Oncol. 2006 Jan 1;24(1):25-35
references.pmid: 16314617
references.citation: N Engl J Med. 2007 Jan 11;356(2):115-24
references.pmid: 17215529
references.citation: Cancer Chemother Pharmacol. 2010 Jul;66(2):357-71
references.pmid: 19967539
references.citation: J Clin Oncol. 2010 May 1;28(13):2137-43
references.pmid: 20368558
references.citation: N Engl J Med. 2007 May 31;356(22):2271-81
references.pmid: 17538086
references.citation: J Clin Oncol. 2009 Sep 1;27(25):4068-75
references.pmid: 19652072
references.citation: Lancet. 2011 Dec 3;378(9807):1931-9
references.pmid: 22056247
references.citation: Int J Urol. 2013 May;20(5):478-83
references.pmid: 23113655
references.citation: N Engl J Med. 2007 Jan 11;356(2):125-34
references.pmid: 17215530
references.citation: J Clin Oncol. 2012 Apr 20;30(12):1371-7
references.pmid: 22430274
references.citation: Cancer. 2012 Mar 1;118(5):1252-9
references.pmid: 21898376
references.citation: J Clin Oncol. 2002 Jan 1;20(1):289-96
references.pmid: 11773181