Can molgramostim enhance the antitumor effects of cytotoxic drugs in patients with advanced sarcomas?

Ann Oncol. 1997 Jul;8(7):637-41. doi: 10.1023/a:1008292010062.

Abstract

Background: A phase I study was designed for the amalgamation of two previously studied antisarcoma regimens (ifosfamide+doxorubicin and mitomycin+doxorubicin+cisplatin) supported by molgramostim. Thus, we hoped to develop a better regimen for the treatment of advanced sarcomas.

Patients and methods: Fifteen adult advanced sarcoma patients and six other patients were registered and sequentially assigned to receive three progressively more myelosuppressive levels of chemotherapy: level I-ifosfamide 2500 mg/m2 + doxorubicin 40 mg/m2 + cisplatin 60 mg/m2 all given on day 0, followed by molgramostim 5 micrograms/kg every 12 hours for 14 days; level II-exactly the same chemotherapy from level I given on day 1 preceded on day 0 by ifosfamide 2500 mg/m2 and an additional four days of molgramostim given on days-6 through-3; level III-same as level II except for the addition of mitomycin 4 mg/m2 immediately prior to cisplatin on day 1. MENSA 500 mg/m2 was given five times on each day that involved ifosfamide treatment. For all levels, treatment was repeated at four-week intervals.

Results: Preliminary results and toxicity were reported three years ago (J Natl Cancer Inst 86: 312-4, 1994). Mature results confirm these unexpectedly favorable results with five advanced sarcoma patients still surviving after more than three years (four more than four years).

Hypothesis: Molgramostim given subcutaneously in a relatively intensive schedule might enhance the antitumor effects initiated by cytotoxic drugs in patients with advanced sarcomas. This idea should be tested formally in phase III studies.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Cisplatin / therapeutic use
  • Doxorubicin / therapeutic use
  • Drug Synergism
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Ifosfamide / therapeutic use
  • Mesna / therapeutic use
  • Mitomycins / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Sarcoma / drug therapy*
  • Survival Analysis

Substances

  • Antineoplastic Agents
  • Mitomycins
  • Recombinant Proteins
  • Doxorubicin
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • molgramostim
  • Mesna
  • Cisplatin
  • Ifosfamide