title: A dose escalation study of docetaxel and oxaliplatin combination in patients with metastatic breast and non-small cell lung cancer.
abstract: OBJECTIVE
  To determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of docetaxel in combination with oxaliplatin (L-OHP) as first-line treatment of patients with advanced breast (ABC) and non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Fifty-two patients (26 with NSCLC and 26 with ABC), who had not received prior chemotherapy for metastatic disease, were enrolled. The patients' median age was 64 years, and 42 (71%) had a performance status (WHO) 0-1. Docetaxel was given as a 1-hour infusion after standard premedication on day 1 and L-OHP as a 2 to 6-hour infusion on day 2 every 3 weeks. Doses were escalated at increments of 10 mg/m2.
  
  
  RESULTS
  The DLT1 was reached at the doses of docetaxel 75 mg/m2 and L-OHP 80 mg/m2. The addition of rhG-CSF permitted further dose escalation (DLT2: docetaxel 90 mg/m2 and L-OHP 130 mg/m2). The dose-limiting events were grade 4 neutropenia, febrile neutropenia, grades 3 or 4 diarrhea and grade 3 fatigue. Out of 239 delivered cycles, grades 3 or 4 neutropenia occurred in 22 (9%) cycles with 5 (2%) neutropenic febrile episodes. There was one septic death. Grades 3 or 4 fatigue was observed in seven (13%) patients and grades 3-4 diarrhea in five (10%). Out of 42 patients evaluable for response, seven (27%) patients with ABC and five (19%) patients with NSCLC experienced a partial response.
  
  
  CONCLUSIONS
  The combination of docetaxel and oxaliplatin is a feasible and well-tolerated regimen. The recommended doses for future phase II studies are 75 mg/m2 for docetaxel on day 1 and 70 mg/m2 for L-OHP on day 2 without rhG-CSF support and 85 mg/m2 and 130 mg/m2, respectively, with rhG-CSF support.
authors.affiliation: Department of Medical Oncology, School of Medicine, University General Hospital of Heraklion, P.O. Box 1352, 71110, Heraklion, Crete, Greece.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Kouroussis
authors.forename: Sophia
authors.initials: S
authors.lastname: Agelaki
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kakolyris
authors.forename: Nick
authors.initials: N
authors.lastname: Androulakis
authors.forename: Kostas
authors.initials: K
authors.lastname: Kalbakis
authors.forename: John
authors.initials: J
authors.lastname: Souglakos
authors.forename: Kostas
authors.initials: K
authors.lastname: Mallas
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Bozionelou
authors.forename: Athanasios
authors.initials: A
authors.lastname: Pallis
authors.forename: Helen
authors.initials: H
authors.lastname: Adamtziki
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D043823:Taxoids
chemical_list: D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; D000077143:Docetaxel; D017239:Paclitaxel