A phase I/II study of sequential, dose-escalated, high dose ifosfamide plus doxorubicin with peripheral blood stem cell support for the treatment of patients with advanced soft tissue sarcomas

Cancer. 1997 Oct 1;80(7):1221-7.


Background: This Phase I/II study investigates increasingly high doses of ifosfamide combined with full dose doxorubicin chemotherapy supported with peripheral blood stem cells (PBSC) and granulocyte-colony stimulating factor (G-CSF) in patients with metastatic soft tissue sarcoma (STS).

Methods: Patients with histologically proven metastatic or advanced adult STS without prior treatment received doxorubicin, 75 mg/m2, on Day 1 followed by 4-day continuous infusion of ifosfamide at 5 consecutive dose levels starting with 8 g/m2 and escalating to 16 g/m2 in increments of 2 g/m2. Three patients per dose level and a maximum of 5 treatment cycles per level at 3-week intervals were planned. Each cycle was followed by G-CSF and retransfusion of PBSC. PBSC separation was performed prior to chemotherapy by steady state mobilization with G-CSF.

Results: Eighteen patients (median age, 45 years, range, 25-57 years) were included, with 4, 3, 4, 4, and 3 patients assigned to Levels 1-5, respectively. Metastatic sites included the lungs in 12 patients (67%), lymph nodes in 8 patients (44%), and the liver in 5 patients (28%). Nine patients (50%) achieved objective responses with 4 complete responses (22%) and 5 partial responses (28%). Lung metastases and a histology of synovial sarcoma or malignant fibrous histiocytoma were favorable features for response to therapy. The median survival for all patients was 13+ months (range, 3-19+ months). Hematotoxicity was manageable and treatment could be administered at a median interval of 24 days. One case of World Health Organization Grade 3 neurotoxicity occurred. Nephrotoxicity was dose-limiting, with 1 patient in Level 4 (WHO Grade 2) and 2 patients in Level 5 (WHO Grade 3).

Conclusions: Multiple cycles of dose-intensive therapy with doxorubicin and high dose ifosfamide can be administered safely with PBSC support. Nephrotoxicity is dose-limiting for ifosfamide at total doses of 16 g/m2. Multiple cycles of high dose chemotherapy at short treatment intervals using ifosfamide at a dose of 14 g/m2 should be investigated further in a neoadjuvant setting in patients with STS.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / adverse effects
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / therapy*
  • Lung Neoplasms / secondary*
  • Lung Neoplasms / therapy*
  • Lymphatic Metastasis
  • Middle Aged
  • Sarcoma / secondary*
  • Sarcoma / therapy*


  • Granulocyte Colony-Stimulating Factor
  • Doxorubicin
  • Ifosfamide