title: Laboratory and clinical evidence of synergistic cytotoxicity of sequential treatment with gemcitabine followed by docetaxel in the treatment of sarcoma.
abstract: OBJECTIVE
  A recent report of the combination of gemcitabine and docetaxel described favorable results in patients with uterine leiomyosarcoma. The objective of this report is to describe experience with this combination in a variety of histologic subtypes of sarcoma. Additionally, cell-culture studies were performed to assess the effect of the sequence of drug administration on colony formation.
  
  
  METHODS
  A medical record review of 35 patients receiving the gemcitabine/docetaxel combination was undertaken. Gemcitabine 675 mg/m(2) intravenously was administered over 90 minutes on days 1 and 8, and docetaxel 100 mg/m(2) intravenously was administered over 60 minutes on day 8 of a 21-day cycle. Cell culture studies using the SAOS-2 osteosarcoma cell line and MCF-7 breast cancer cell line were also performed. Gemcitabine and docetaxel were added to cells either simultaneously for 24 hours, gemcitabine for 24 hours followed by docetaxel for 24 hours, or the reverse sequence.
  
  
  RESULTS
  Thirty-five patients were treated. Five complete responses and 10 partial responses were observed for an overall response rate of 43%. Responses occurred in uterine, extremity, and retroperitoneal leiomyosarcoma, osteosarcomas, angiosarcomas, malignant fibrous histiocytomas, malignant peripheral-nerve sheath tumors, and Ewing's sarcoma. In the cell culture studies, gemcitabine followed by docetaxel provided synergy. In contrast, the administration of drugs simultaneously resulted in antagonism, and docetaxel followed by gemcitabine provided mixed results.
  
  
  CONCLUSIONS
  The combination of gemcitabine and docetaxel seems to be active in a variety of sarcomas. A multicenter, randomized clinical trial in soft tissue sarcoma comparing gemcitabine alone with this combination, is ongoing.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109, USA.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Leu
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Ostruszka
authors.forename: Donna
authors.initials: D
authors.lastname: Shewach
authors.forename: Mark
authors.initials: M
authors.lastname: Zalupski
authors.forename: Vernon
authors.initials: V
authors.lastname: Sondak
authors.forename: J Sybil
authors.initials: JS
authors.lastname: Biermann
authors.forename: Julia Shin-Jung
authors.initials: JS
authors.lastname: Lee
authors.forename: Carol
authors.initials: C
authors.lastname: Couwlier
authors.forename: Krisinda
authors.initials: K
authors.lastname: Palazzolo
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Baker
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000093542:Gemcitabine