A randomised, open-label, phase II study of neo/adjuvant doxorubicin and ifosfamide versus gemcitabine and docetaxel in patients with localised, high-risk, soft tissue sarcoma

Eur J Cancer. 2015 Sep;51(13):1794-802. doi: 10.1016/j.ejca.2015.05.010. Epub 2015 Jun 9.

Abstract

Background: Doxorubicin and ifosfamide (AI) is standard therapy for high-risk soft tissue sarcoma (STS) but often causes severe toxicities resulting in hospitalisation. Gemcitabine and docetaxel (GD) has efficacy in metastatic STS and may be better tolerated. We conducted a study to compare toxicities and efficacies of these regimens.

Methods: This open-label, phase II, single institution trial randomised 80 patients with localised, resectable, high grade STS ⩾ 5 cm to either neo/adjuvant AI or GD. AI was doxorubicin (75 mg/m(2)) and ifosfamide (2.5 g/m(2)/d) on days 1-3 with mesna 500 mg/m(2)/dose. GD was gemcitabine 900 mg/m(2) on days 1, 8 and docetaxel 100mg/m(2) day 8. Both arms included filgrastim. The primary end-point was hospitalisation rate. Secondary end-points included disease-free survival (DFS) and overall survival (OS).

Results: Between November 2004 and August 2012, 80 evaluable patients were randomised, 37 to AI and 43 to GT. In the AI arm, 13/37 (35%) patients were hospitalised versus 11/43 (26%) in the GD arm (p=0.25). Hospitalisation rates were not significantly different after adjusting for age, gender, location, chemotherapy and number of cycles (p=0.17). The 2-year and median DFS in the AI arm were 57% and 37 months, respectively, and 74% and not yet reached, respectively, in the GD arm. The most common serious adverse events with AI were haematologic. Metabolic derangements and constitutional symptoms were most common with GD.

Conclusions: Hospitalisation rate was less with GD but not statistically significant. There was a trend towards longer DFS with GD, and the regimen was tolerable, suggesting GD merits further study.

Keywords: Docetaxel; Doxorubicin; Gemcitabine; Ifosfamide; Neo(adjuvant) chemotherapy; Soft tissue sarcoma.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease Progression
  • Disease-Free Survival
  • Docetaxel
  • Doxorubicin / administration & dosage
  • Female
  • Gemcitabine
  • Hospitalization
  • Humans
  • Ifosfamide / administration & dosage
  • Kaplan-Meier Estimate
  • Male
  • Michigan
  • Middle Aged
  • Neoadjuvant Therapy* / adverse effects
  • Neoadjuvant Therapy* / mortality
  • Proportional Hazards Models
  • Radiotherapy, Adjuvant
  • 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*
  • Taxoids / administration & dosage
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Taxoids
  • Deoxycytidine
  • Docetaxel
  • Doxorubicin
  • Ifosfamide
  • Gemcitabine