title: First safety and response results of a randomized phase III study with liposomal platin in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN).
abstract: BACKGROUND
  Cisplatin is one of the most active chemotherapeutic agents used in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN). However, its clinical efficacy is limited by its renal and hematotoxicity profile. In a randomized, multicenter phase III trial, we replaced conventional cisplatin by a liposomal formulation of cisplatin (lipoplatin) and compared the safety and efficacy profiles of patients in the two treatment arms.
  
  
  METHODS
  Main inclusion criteria were: histologically confirmed SCCHN, age between 18-75 years with sufficient renal function. Main endpoints for this interims analysis were hemato- and nephrotoxicity. First response data were collected.
  
  
  RESULTS
  Forty-six patients were evaluable for outcome and toxicity. Grade III and IV hematotoxicity were more frequent in the cisplatin arm (31.7% vs. 12%), with grade IV leucopenia occurring in 22.2%. However, 16% of the patients in that treatment arm experienced grade III anemia compared to only 9.5% treated with the cisplatin regimen. A total 4% of the patients in the lipoplatin arm developed grade IV neuropathy, whereas in the cisplatin arm, 19% developed grade III neuropathy and none developed grade IV. The renal toxicity profile of both drugs also showed marked differences. In the cisplatin arm, 23.8% of patients suffered grade III toxicity. In contrast, no grade III or IV renal toxicity occurred in patients treated with lipoplatin. The efficacy results showed 38.8% objective partial remission in the cisplatin arm vs. 19% in the lipoplatin arm. However 64% of the patients achieved stable disease while being treated with lipoplatin/5-fluorouracil (5-FU), vs. 50% in the cisplatin/5-FU arm.
  
  
  CONCLUSIONS
  Liposomal cisplatin seems to reduce both the renal and hematological toxicity to a clinically relevant extent as compared to conventional cisplatin. The clinical benefit rate is similar for both regimens.
authors.affiliation: Medizinische Klinik und Poliklinik mit Schwerpunkt Onkologie und Hämatologie Charité, Campus Mitte, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin 10117 Berlin, Germany.
authors.forename: C F
authors.initials: CF
authors.lastname: Jehn
authors.forename: T
authors.initials: T
authors.lastname: Boulikas
authors.forename: A
authors.initials: A
authors.lastname: Kourvetaris
authors.forename: G
authors.initials: G
authors.lastname: Kofla
authors.forename: K
authors.initials: K
authors.lastname: Possinger
authors.forename: D
authors.initials: D
authors.lastname: Lüftner
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: C503131:lipoplatin; D002945:Cisplatin; D005472:Fluorouracil