title: A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer.
abstract: BACKGROUND
  Serum interleukin (IL)-6 levels correlate with disease outcomes in renal cell carcinoma (RCC) patients. Siltuximab, a chimeric, murine-human mAb against IL-6, was evaluated in a three-part phase I/II study in patients with progressive metastatic RCC.
  
  
  METHODS
  In part 1, 11 patients received 1, 3, 6, or 12mgkg-¹ at weeks 1, 4 and q2w × 2 thereafter; in part 2, 37 patients randomly received 3 or 6 mgkg-¹ q3w × 4; in part 3, 20 low-risk patients received 6mgkg-¹ q2w × 6. Modified WHO response criteria were assessed at weeks 7, 11, the 6-week follow-up, and when clinically indicated.
  
  
  RESULTS
  Siltuximab was well tolerated overall, with no maximum tolerated dose or immune response observed. In all, 5 out of 11, 17 out of 37, and 9 out of 20 patients in parts 1, 2, and 3, respectively, received extended treatment beyond 4-6 initial infusions. In part 2, stable disease (SD) (≥11weeks) or better was achieved by 11 out of 17 (65%) 3 mgkg-¹ treated patients (one partial response (PR) ~8 months, 10 SD) and 10 out of 20 (50%) 6mgkg-¹ treated patients (10 SD). In part 3, documented complete or PR was not observed, but 13 out of 20 (65%) patients achieved SD.
  
  
  CONCLUSIONS
  Siltuximab stabilised disease in >50% of progressive metastatic RCC patients. One PR was observed. Given the favourable safety profile of siltuximab and poor correlation of tumour shrinkage with clinical benefit demonstrated for other non-cytotoxic therapies, further evaluation of dose-escalation strategies and/or combination therapy may be considered for patients with RCC.
authors.affiliation: Service d'Hématologie et d'Oncologie Médicale, CHU Saint-Eloi, BT 509-INSERM U847, CHRU Montpellier et Université Montpelllier I, Montpellier, France.
authors.forename: J-F
authors.initials: JF
authors.lastname: Rossi
authors.forename: S
authors.initials: S
authors.lastname: Négrier
authors.forename: N D
authors.initials: ND
authors.lastname: James
authors.forename: I
authors.initials: I
authors.lastname: Kocak
authors.forename: R
authors.initials: R
authors.lastname: Hawkins
authors.forename: H
authors.initials: H
authors.lastname: Davis
authors.forename: U
authors.initials: U
authors.lastname: Prabhakar
authors.forename: X
authors.initials: X
authors.lastname: Qin
authors.forename: P
authors.initials: P
authors.lastname: Mulders
authors.forename: B
authors.initials: B
authors.lastname: Berns
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007167:Immunotherapy; D015850:Interleukin-6 / Q000276:immunology*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors; C504234:siltuximab
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