title: Feasibility and efficacy of gemcitabine and docetaxel combination chemotherapy for bone and soft tissue sarcomas: multi-institutional retrospective analysis of 134 patients.
abstract: BACKGROUND
  Bone and soft tissue sarcomas (BSTS) are rare malignant tumors. Recently, the combination of gemcitabine and docetaxel (GD) was shown to have activity as second-line setting in BSTS. However, the efficacy as first-line and adjuvant settings and precise profiles of adverse events in Japanese patients are not known yet. In the present study, the feasibility and efficacy of GD in patients with BSTS were investigated.
  
  
  METHODS
  Patients with BSTS treated with GD in our institutions were retrospectively analyzed. Information regarding clinical features, adverse events, and outcome was collected and statistically studied. Factors related to survival were analyzed using log-rank test and Cox proportional hazard regression method.
  
  
  RESULTS
  A total of 134 patients were analyzed. GD was carried out as adjuvant setting in 9, first-line in 23, second-line in 56, and third-or-greater line in 46 patients. The response rate (RR) for all patients was 9.7%. RR for the patients treated as adjuvant or first-line setting was 18.8%, whereas that as second-or-greater line was 6.9%. The median progression-free survival (PFS) and overall survival (OS) of all patients were 4.8 (95% CI 3.5-6.1) and 16.4 (95% CI 9.8-22.9) months, respectively. Survival tended to be better in the patients treated as first-line than in those treated as second-or-greater line. Multivariate analysis demonstrated that history of prior chemotherapy (p = 0.046) and response to GD (p = 0.009) was significantly associated with PFS and OS, respectively. The leucopenia and neutropenia were the most frequent adverse events, and grade 3 or 4 leucopenia and neutropenia were observed in 69.4 and 72.4% of the patients. Grade 2 or 3 pneumonitis was observed in one (0.7%) and four (3.0%) patients, respectively. All the patients with pneumonitis had experienced prior chemotherapy and/or radiotherapy.
  
  
  CONCLUSIONS
  GD used as both first- and second/later line is effective chemotherapy for a proportion of patients with advanced BSTS. Higher response rate and better outcome was achieved in chemotherapy-naïve patients. This regimen is associated with high incidence of severe hematological toxicity, as well as the risk of severe pneumonitis, especially in pre-treated patients. GD is promising for further analysis by phase III study for the patients with BSTS.
authors.affiliation: Department of Orthopaedic Surgery, Oita University, Idaigaoka 1-1, Hasama, Yufu, Oita, 879-5593, Japan. ktanaka@oita-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Orthopaedic Surgery, Osaka Medical Center, Osaka, 537-8511, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Joyama
authors.affiliation: Department of Orthopaedic Surgery, National Cancer Center Hospital, Tokyo, 104-0045, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Chuman
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido Cancer Center, Sapporo, 003-0804, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hiraga
authors.affiliation: Department of Orthopaedic Surgery, Keio University, Tokyo, 160-0016, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Morioka
authors.affiliation: Department of Orthopaedic Surgery, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University, Sendai, 980-8575, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Hosaka
authors.affiliation: Department of Orthopaedic Surgery, Shizuoka Cancer Center, Shizuoka, 411-0934, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Orthopaedic Surgery, Hiroshima University, Hiroshima, 734-0037, Japan.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Orthopaedic Surgery, Niigata Cancer Center Hospital, Niigata, 951-8133, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hatano
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University, Sapporo, 060-8556, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Kaya
authors.affiliation: Department of Orthopaedic Surgery, Kyoto University, Kyoto, 606-8501, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Toguchida
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University, Nagoya, 466-8550, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishida
authors.affiliation: Department of Orthopaedic Surgery, Gifu University, Gifu, 501-1194, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Nagano
authors.affiliation: Department of Orthopaedic Surgery, Oita University, Idaigaoka 1-1, Hasama, Yufu, Oita, 879-5593, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsumura
authors.affiliation: Department of Orthopaedic Surgery, Kyushu University, Fukuoka, 812-8582, Japan.|Present address: Kyushu Rosai Hospital, Kitakyushu, 800-0296, Japan.
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D000077143:Docetaxel; D005240:Feasibility Studies; D006801:Humans; D007564:Japan; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012516:Osteosarcoma / Q000188:drug therapy*; D011014:Pneumonia / Q000139:chemically induced; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy*; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D043823:Taxoids; D050257:Tubulin Modulators; D003841:Deoxycytidine; D000077143:Docetaxel; D000093542:Gemcitabine
keywords: Adjuvant chemotherapy; Adverse events; Docetaxel; Gemcitabine; Sarcoma