title: Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007): Phase I study of patients with squamous cell carcinoma of the head and neck and anal canal: preliminary evidence of clinical activity.
abstract: BACKGROUND
  This study was designed to determine the feasibility, maximum tolerated dose, and toxicities of intraarterial administration of paclitaxel-albumin nanoparticles in patients with advanced head and neck and recurrent anal canal squamous cell carcinoma. Antitumor activity also was assessed.
  
  
  METHODS
  Forty-three patients (31 with advanced head and neck and 12 with recurrent anal canal squamous cell carcinoma) were treated intraarterially with ABI-007 every 4 weeks for 3 cycles. In total, 120 treatment cycles were completed, 86 in patients with head and neck carcinoma (median, 3 cycles; range, 1-4) and 34 in patients with anal canal carcinoma (median, 3 cycles; range, 1-4). ABI-007 was compared preliminarily with Taxol for in vitro cytostatic activity. Increasing dose levels from 120 to 300 mg/m2 were studied in 18 patients. Pharmacokinetic profiles after intraarterial administration were obtained in a restricted number of patients.
  
  
  RESULTS
  The dose-limiting toxicity of ABI-007 was myelosuppression consisting of Grade 4 neutropenia in 3 patients. Nonhematologic toxicities included total alopecia (30 patients), gastrointestinal toxicity (3 patients, Grade 2), skin toxicity (5 patients, Grade 2), neurologic toxicity (4 patients, Grade 2) ocular toxicity (1 patient, Grade 2), flu-like syndrome (7 patients, Grade 2; 1 patient, Grade 3). In total, 120 transfemoral, percutaneous catheterization procedure-related complications occurred only during catheterization of the neck vessels in 3 patients (2 TIA, 1 hemiparesis) and resolved spontaneously.
  
  
  CONCLUSIONS
  Intraarterial administration of ABI-007 by percutaneous catheterization does not require premedication, is easy and reproducible, and has acceptable toxicity. The maximum tolerated dose in a single administration was 270 mg/m2. Most dose levels showed considerable antitumor activity (42 assessable patients with 80.9% complete response and partial response). The recommended Phase II dose is 230 mg/m2 every 3 weeks.
authors.affiliation: Department of Radiology, Istituto Nazionale Tumori, Milano, Italy. damascelli@istitutotumori.mi.it
authors.forename: B
authors.initials: B
authors.lastname: Damascelli
authors.forename: G
authors.initials: G
authors.lastname: Cantù
authors.forename: F
authors.initials: F
authors.lastname: Mattavelli
authors.forename: P
authors.initials: P
authors.lastname: Tamplenizza
authors.forename: P
authors.initials: P
authors.lastname: Bidoli
authors.forename: E
authors.initials: E
authors.lastname: Leo
authors.forename: F
authors.initials: F
authors.lastname: Dosio
authors.forename: A M
authors.initials: AM
authors.lastname: Cerrotta
authors.forename: G
authors.initials: G
authors.lastname: Di Tolla
authors.forename: L F
authors.initials: LF
authors.lastname: Frigerio
authors.forename: F
authors.initials: F
authors.lastname: Garbagnati
authors.forename: R
authors.initials: R
authors.lastname: Lanocita
authors.forename: A
authors.initials: A
authors.lastname: Marchianò
authors.forename: G
authors.initials: G
authors.lastname: Patelli
authors.forename: C
authors.initials: C
authors.lastname: Spreafico
authors.forename: V
authors.initials: V
authors.lastname: Tichà
authors.forename: V
authors.initials: V
authors.lastname: Vespro
authors.forename: F
authors.initials: F
authors.lastname: Zunino
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002368:Castor Oil / Q000031:analogs & derivatives*; D002626:Chemistry, Pharmaceutical; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D010316:Particle Size; D013501:Surface-Active Agents; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D013501:Surface-Active Agents; C023040:polyethoxylated castor oil; D002368:Castor Oil; D017239:Paclitaxel