title: A phase II trial comparing pazopanib with doxorubicin as first-line treatment in elderly patients with metastatic or advanced soft tissue sarcoma (EPAZ): study protocol for a randomized controlled trial.
abstract: Anthracycline-based treatment remains the backbone of chemotherapy for nonresectable soft tissue sarcomas (STS). More than 30 % of patients with STS are aged 60 years or older, limiting the choice of treatment to single-agent approaches for this elderly population. Hematological toxicity is frequent during doxorubicin monotherapy, grade 4 neutropenia is reported in 34 %, with a febrile neutropenia rate of 9 % in STS. We assume that comorbidities in the elderly population may limit tolerability of doxorubicin, and novel agents may improve tolerability and health-related quality of life while maintaining efficacy. We therefore investigated whether the tyrosine kinase inhibitor pazopanib exerts such a clinical benefit in elderly patients with STS (pazopanib for elderly [the EPAZ study]).
  
  
  
  This study is a randomized, controlled, open-label, multicenter, phase II noninferiority trial in which pazopanib 800 mg once daily is being compared six cycles of intravenous doxorubicin 75 mg/m(2) as first-line treatment in elderly patients (≥60 years) with metastatic or advanced STS. A total of 120 patients will be randomized 1:2 to receive doxorubicin or pazopanib, stratified by Eastern Cooperative Oncology Group performance status (0-1 vs. 2) and liposarcoma histology (yes vs. no). The primary endpoint is progression-free survival based on local tumor assessment according to Response Evaluation Criteria in Solid Tumors criteria. Secondary endpoints include grade 4 neutropenia and febrile neutropenia in hierarchical order, as well as overall survival, objective response rate, health-related quality of life, and geriatric assessments.
  
  
  
  Pazopanib is associated with promising tolerability according to previous studies and may offer a significant clinical advantage in first-line treatment of STS compared with doxorubicin. The elderly population seems especially appealing for such an approach, since these patients are not suitable for aggressive combination therapy. The EPAZ study will confirm whether pazopanib may be an alternative to toxic chemotherapy for elderly patients with STS.
  
  
  
  ClinicalTrials.gov NCT01861951 ; registered on 11 April 2013. EudraCT 2011-004168-30; registered on 4 June 2012.
authors.affiliation: Institute for Biostatistics, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Karch
authors.affiliation: Institute for Biostatistics, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Koch
authors.affiliation: Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. gruenwald.viktor@mh-hannover.de.
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
mesh_terms: D000367:Age Factors; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001530:Belgium; D002985:Clinical Protocols; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D015577:Geriatric Assessment; D005858:Germany; D006801:Humans; D007191:Indazoles; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D012107:Research Design; D012307:Risk Factors; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D004317:Doxorubicin
keywords: Doxorubicin; Elderly; Noninferiority; Pazopanib; Soft tissue sarcoma