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


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).


OBJECTIVE
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.
Edmonson
J H
JH
Division of Medical oncology, Mayo Clinic, Rochester, MN, USA.
Long
H J
HJ
Kvols
L K
LK
Mann
B S
BS
Grill
J P
JP
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D015080:Mesna / Q000627:therapeutic use; D008937:Mitomycins / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012509:Sarcoma / Q000188:drug therapy*; D016019:Survival Analysis
D000970:Antineoplastic Agents; D008937:Mitomycins; D011994:Recombinant Proteins; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C082430:molgramostim; D015080:Mesna; D002945:Cisplatin; D007069:Ifosfamide