title: Phase I trial of PEG-interferon and recombinant IL-2 in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  Pegylated interferon alpha-2b (PEG-Intron) is a conjugate of polyethylene glycol (PEG) and interferon alpha-2b, has a prolonged half-life, and an increased area under the curve (AUC) for interferon alpha-2b. The combination of PEG-Intron with recombinant interleukin-2 (rIL-2) was investigated in a phase 1 trial. To determine the maximal tolerable dose (MTD) and preliminary efficacy of concurrent subcutaneous (SC) administration of PEG-Intron and rIL-2 in patients with metastatic renal cell carcinoma (RCC).
  
  
  METHODS
  Cohorts of 3-6 patients received escalating doses of PEG-Intron (I-1.5, II- 1.5, III-3.0, IV-3.0, V-4.5 microg/kg SC) given weekly in combination with rIL-2 administered three times weekly (TIW) for 6 weeks. rIL-2 dose levels were escalated in weeks 1 and 4 (I-10.0, II-15.0, III-15.0, IV-20.0, V-20.0 MIU/m(2) SC), and 5.0 MIU/m(2) SC TIW was administered during weeks 2, 3, 5 and 6.
  
  
  RESULTS
  Thirty-four patients (24 men; 10 women) were accrued at dose levels I (n = 4), II (n = 4), III (n = 6), IV (n = 14), and V (n = 6) between October 2000 and October 2002. All but one patient had prior nephrectomy (n = 33) and all but one patient (97%) had received no prior systemic therapy. Patients received a median of four cycles of treatment (range 1-9). Dose limiting toxicity occurred at dose level V and included grade 4 neutropenia and hypoxemia. A partial response was found in 5 pts (15%). Median progression-free and overall survival were 9.0 (95% C.I. 5.6-13.1 months) and 31.9 months (95% C.I. 17.2-61.9 months), respectively.
  
  
  CONCLUSIONS
  The combination of PEG-Interferon and SC rIL-2 can be administered with acceptable toxicity.
authors.affiliation: Experimental Therapeutics Program, Department of Hematology and Medical Oncology/ R33, The Cleveland Clinic Taussig Cancer Center, 9500 Euclid Ave, Cleveland, OH, 44195, USA. georges2@ccf.org
authors.forename: Saby
authors.initials: S
authors.lastname: George
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
authors.forename: Tarek
authors.initials: T
authors.lastname: Mekhail
authors.forename: Laura
authors.initials: L
authors.lastname: Wood
authors.forename: James
authors.initials: J
authors.lastname: Finke
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Bukowski
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007376:Interleukin-2 / 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; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b