title: Multimodal treatment with doxorubicin, cisplatin, and ifosfamide for the treatment of advanced or metastatic uterine leiomyosarcoma: a unicentric experience.
abstract: OBJECTIVE
  Uterine leiomyosarcoma (ULMS) is a rare gynecologic malignancy characterized by a poor prognosis due to a high rate of local and metastatic recurrences. Chemotherapy with doxorubicin or ifosfamide or both is associated with a 10% to 30% objective response rate. We report a monocentric experience with doxorubicin, cisplatin, and ifosfamide (API) combination in the setting of multimodal treatment of advanced or metastatic ULMS.
  
  
  METHODS
  This monocentric retrospective study included patients with metastatic or locally advanced ULMS with a physiological age younger than 65 years treated in first line with a multimodal aggressive approach with API chemotherapy. Treatment consisted of doxorubicin 50 mg/m2 d1, ifosfamide 3 g/m2 per day d1d2 plus mesna, cisplatin 75 mg/m2 d3, plus G-CSF; every 3 weeks up to 6 cycles. Surgery, radiation therapy, or radiofrequency ablation therapy of metastatic sites was associated whenever possible.
  
  
  RESULTS
  Thirty-eight patients received API for metastatic or locally advanced ULMS. Median age was 51 years (40-64 years); 4 (11%) patients were treated for a locally advanced disease and 34 (89%) for metastatic disease. Sixteen patients responded (4 complete responses+12 partial responses) among 33 evaluable patients (objective response rate, 48%); 8 and 9 patients had, respectively, stable and progressive disease. Twelve patients had surgeries with 9 surgical complete responses and 3 surgical partial responses. Median progression-free and overall survival in the whole population were 9.8 and 27 months, respectively. Main grade 3-4 toxicities in 38 patients were neutropenia (74%), thrombocytopenia (60%), anemia (55%), fatigue (18%), and vomiting (13%). Febrile neutropenia was observed in 37% of patients.
  
  
  CONCLUSIONS
  Despite the toxicity observed, API is an effective treatment which compares favorably with other first-line therapies for patients with metastatic or advanced ULMS.
authors.affiliation: *Gynecologic Oncology Unit, †Biostatistics Department, ‡Pathology Department, §Radiology Department, ∥ Radiation Therapy Department, and ¶Surgery Department, Institut Gustave Roussy, Villejuif, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Hadoux
authors.forename: Annie
authors.initials: A
authors.lastname: Rey
authors.forename: Pierre
authors.initials: P
authors.lastname: Duvillard
authors.forename: Catherine
authors.initials: C
authors.lastname: Lhommé
authors.forename: Corinne
authors.initials: C
authors.lastname: Balleyguier
authors.forename: Christine
authors.initials: C
authors.lastname: Haie-Meder
authors.forename: Philippe
authors.initials: P
authors.lastname: Morice
authors.forename: Youssef
authors.initials: Y
authors.lastname: Tazi
authors.forename: Alexandra
authors.initials: A
authors.lastname: Leary
authors.forename: Christine
authors.initials: C
authors.lastname: Larue
authors.forename: Patricia
authors.initials: P
authors.lastname: Pautier
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017115:Catheter Ablation; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D013509:Gynecologic Surgical Procedures; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D016019:Survival Analysis; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000628:therapy
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide