Ten-year follow-up results of perioperative chemotherapy with doxorubicin and ifosfamide for high-grade soft-tissue sarcoma of the extremities: Japan Clinical Oncology Group study JCOG0304

BMC Cancer. 2019 Sep 6;19(1):890. doi: 10.1186/s12885-019-6114-2.


Background: Soft-tissue sarcomas (STS) are rare malignant tumors those are resistant to chemotherapy. We have previously reported the 3-year follow-up result on the efficacy of perioperative chemotherapy with doxorubicin (DXR) and ifosfamide (IFM) for high-risk STS of the extremities (JCOG0304). In the present study, we analyzed the 10-year follow-up results of JCOG0304.

Methods: Patients with operable, high-risk STS (T2bN0M0, AJCC 6th edition) of the extremities were treated with 3 courses of preoperative and 2 courses of postoperative chemotherapy, which consisted of 60 mg/m2 of DXR plus 10 g/m2 of IFM over a 3-week interval. The primary study endpoint was progression-free survival (PFS) estimated by Kaplan-Meier methods. Prognostic factors were evaluated by univariable and multivariable Cox proportional hazards model.

Results: A total of 72 patients were enrolled between March 2004 and September 2008, with 70 of these patients being eligible. The median follow-up period was 10.0 years for all eligible patients. Local recurrence and distant metastasis were observed in 5 and 19 patients, respectively. The 10-year PFS was 65.7% (95% CI: 53.4-75.5%) with no PFS events being detected during the last 5 years of follow-up. The 10-year overall survival was 78.1% (95% CI: 66.3-86.2%). Secondary malignancy was detected in 6 patients. The subgroup analysis demonstrated that there was significant difference in survival with regard to primary tumor size.

Conclusions: Only a few long-term results of clinical trials for perioperative chemotherapy treatment of STS have been reported. Our results demonstrate that the 10-year outcome of JCOG0304 for patients with operable, high-risk STS of the extremities was stable and remained favorable during the last 5 years of follow-up.

Trial registration: This trial was registered at the UMIN Clinical Trials Registry as C000000096 on August 30, 2005.

Keywords: 10-year follow-up; Doxorubicin and ifosfamide; Extremity; Perioperative chemotherapy; Soft tissue sarcoma; Survival.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Clinical Trials as Topic
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use
  • Drug Administration Schedule
  • Extremities / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / therapeutic use
  • Japan
  • Male
  • Odds Ratio
  • Perioperative Period
  • Sarcoma / drug therapy*
  • Sarcoma / mortality
  • Sarcoma / pathology
  • Sarcoma / surgery
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / mortality
  • Soft Tissue Neoplasms / pathology
  • Soft Tissue Neoplasms / surgery
  • Survival Rate
  • Treatment Outcome


  • Doxorubicin
  • Ifosfamide