Perioperative Adriamycin plus ifosfamide vs. gemcitabine plus docetaxel for high-risk soft tissue sarcomas: randomised, phase II/III study JCOG1306

Br J Cancer. 2022 Nov;127(8):1487-1496. doi: 10.1038/s41416-022-01912-5. Epub 2022 Jul 23.

Abstract

Background: This randomised phase II/III trial aimed to determine whether perioperative chemotherapy with gemcitabine plus docetaxel (GD) is non-inferior to the standard Adriamycin plus ifosfamide (AI) in terms of overall survival (OS) in patients with soft tissue sarcoma (STS).

Methods: Patients with localised high-risk STS in the extremities or trunk were randomised to receive AI or GD. The treatments were repeated for three preoperative and two postoperative courses. The primary endpoint was OS.

Results: Among 143 enrolled patients who received AI (70 patients) compared to GD (73 patients), the estimated 3-year OS was 91.4% for AI and 79.2% for GD (hazard ratio 2.55, 95% confidence interval: 0.80-8.14, P = 0.78), exceeding the prespecified non-inferiority margin in the second interim analysis. The estimated 3-year progression-free survival was 79.1% for AI and 59.1% for GD. The most common Grade 3-4 adverse events in the preoperative period were neutropenia (88.4%), anaemia (49.3%), and febrile neutropenia (36.2%) for AI and neutropenia (79.5%) and febrile neutropenia (17.8%) for GD.

Conclusions: Although GD had relatively mild toxicity, the regimen-as administered in this study-should not be considered a standard treatment of perioperative chemotherapy for high-risk STS in the extremities and trunk.

Clinical trial registration: jRCTs031180003.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Docetaxel / therapeutic use
  • Doxorubicin
  • Febrile Neutropenia*
  • Gemcitabine
  • Humans
  • Ifosfamide / adverse effects
  • Sarcoma* / drug therapy
  • Sarcoma* / surgery
  • Soft Tissue Neoplasms*

Substances

  • Deoxycytidine
  • Docetaxel
  • Doxorubicin
  • Ifosfamide
  • Gemcitabine