51. 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.
- Author
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Davis EJ, Chugh R, Zhao L, Lucas DR, Biermann JS, Zalupski MM, Feng M, Wong SL, Jacobson J, Zyczynski L, Reinke D, Metko G, Baker LH, and Schuetze SM
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Chemotherapy, Adjuvant, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Disease Progression, Disease-Free Survival, Docetaxel, Doxorubicin administration & dosage, Female, Hospitalization, Humans, Ifosfamide administration & dosage, Kaplan-Meier Estimate, Male, Michigan, Middle Aged, Proportional Hazards Models, Radiotherapy, Adjuvant, Sarcoma mortality, Sarcoma pathology, Soft Tissue Neoplasms mortality, Soft Tissue Neoplasms pathology, Taxoids administration & dosage, Time Factors, Treatment Outcome, Young Adult, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoadjuvant Therapy adverse effects, Neoadjuvant Therapy mortality, Sarcoma drug therapy, Sarcoma surgery, Soft Tissue Neoplasms drug therapy, Soft Tissue Neoplasms surgery
- 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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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