title: A phase I trial combining oral cisplatin (CP Ethypharm) with radiotherapy in patients with locally advanced head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  To determine the maximum tolerated dose (MTD) of oral cisplatin (CP Ethypharm®) in combination with radiotherapy in head and neck squamous cell carcinoma (HNSCC) and the recommended dose for phase II trials.
  
  
  METHODS
  Phase I, multicenter, open-labelled, non-comparative and dose escalating trial. CP Ethypharm® was administered on five consecutive days every other week for 7 weeks (4 treatment cycles) in combination with radiotherapy. Eighteen patients with locally advanced HNSCC were allocated to four cisplatin dose levels: 10 mg/m(2)/day: 4 patients; 15 mg/m(2)/day: 4, 20 mg/m(2)/day: 5 and 25 mg/m(2)/day: 5. The inclusion of patients was dictated by occurrence of dose limiting toxicities (DLTs) at each dosing level.
  
  
  RESULTS
  The most frequently experienced AEs were gastrointestinal (GI) disorders. Five DLTs were observed, including three at 25 mg/m(2) level (two grade 2 renal toxicities, one grade 3 GI and renal toxicities), one at 20 mg/m(2) level (grade 3 GI disorders), one at 10 mg/m(2) level (grade 4 mucositis). PK analysis showed no significant difference of C(max) values between day 1 and day 5 of treatment at each dose level (total & ultrafilterable platinum).
  
  
  CONCLUSIONS
  Due to 3 DLTs experienced at 25 mg/m(2)/day, MTD was reached and the recommended dose for phase II studies was determined as 20 mg/m(2)/day.
authors.affiliation: Institute Gustave-Roussy, Villejuif, France.
authors.forename: Yungan
authors.initials: Y
authors.lastname: Tao
authors.forename: Keyvan
authors.initials: K
authors.lastname: Rezaï
authors.forename: Etienne
authors.initials: E
authors.lastname: Brain
authors.forename: Atoussa
authors.initials: A
authors.lastname: Etessami
authors.forename: Antoine
authors.initials: A
authors.lastname: Lusinchi
authors.forename: Stephane
authors.initials: S
authors.lastname: Temam
authors.forename: Saik
authors.initials: S
authors.lastname: Urien
authors.forename: Marie-Louise Vo
authors.initials: ML
authors.lastname: Van
authors.forename: Françoise
authors.initials: F
authors.lastname: Vauzelle-Kervroedan
authors.forename: François
authors.initials: F
authors.lastname: Lokiec
authors.forename: Nicolas
authors.initials: N
authors.lastname: Daly-Schveitzer
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
mesh_terms: D000284:Administration, Oral; D002277:Carcinoma / Q000188:drug therapy / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy; D011879:Radiotherapy Dosage; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D002945:Cisplatin