title: A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma.
abstract: BACKGROUND
  The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS.
  
  
  METHODS
  Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m(2) iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m(2) day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA.
  
  
  RESULTS
  Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far.
  
  
  CONCLUSIONS
  The current protocol is feasible for achieving local control rates, as well as OS and DFS comparable to previously published data on neo-/adjuvant chemotherapy in this setting. However, the definitive role of chemotherapy remains unclear in the absence of large, randomized trials. Therefore, the current regimen can only be recommended within a clinical study, and a possibly increased risk of secondary leukemias has to be taken into account.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01382030, EudraCT 2004-002501-72.
authors.affiliation: Department of Hematology, Oncology, and Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. thomas.schmitt@med.uni-heidelberg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitt
authors.forename: Burkhard
authors.initials: B
authors.lastname: Lehner
authors.forename: Bernd
authors.initials: B
authors.lastname: Kasper
authors.forename: Marc
authors.initials: M
authors.lastname: Bischof
authors.forename: Falk
authors.initials: F
authors.lastname: Roeder
authors.forename: Sascha
authors.initials: S
authors.lastname: Dietrich
authors.forename: Antonia
authors.initials: A
authors.lastname: Dimitrakopoulou-Strauss
authors.forename: Ludwig G
authors.initials: LG
authors.lastname: Strauss
authors.forename: Gunhild
authors.initials: G
authors.lastname: Mechtersheimer
authors.forename: Patrick
authors.initials: P
authors.lastname: Wuchter
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Egerer
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D011092:Polyethylene Glycols; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D012509:Sarcoma / Q000401:mortality / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000401:mortality / Q000628:therapy*; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D005047:Etoposide; D004317:Doxorubicin; D000069585:Filgrastim; D007069:Ifosfamide