Phase II trial of dacarbazine, mitomycin, doxorubicin, and cisplatin with sargramostim in uterine leiomyosarcoma: a Gynecologic Oncology Group study.
OBJECTIVE
Following a reported 23% response rate (RR) for mitomycin (M), doxorubicin (A), and cisplatin (P) and preliminary data suggesting a superior RR for dacarbazine (D) + MAP + sargramostim, the Gynecologic Oncology Group (GOG) conducted a phase II trial of DMAP + sargramostim in patients with advanced uterine leiomyosarcoma.


METHODS
Eligibility required measurable disease, a GOG performance score of 0-2, and recovery from surgery/radiotherapy. Treatment consisted of sargramostim 250 microg/m2 SC q 12 h days -6 through -3, followed by D 750 mg/m2 IV over 2 h, M 6 mg/m2 IV, A 40 mg/m2 IV and P 60 mg/m2 IV over 2 h on day 1, followed by sargramostim 250 microg/m2 SC days 2-15. Cycles were repeated q 28 days (if ANC > or = 1500/microl and platelets > or = 100,000/microl) until disease progression or toxicity prevented further therapy. Doses were to be reduced by 20% for grade 4 neutropenia >7 days or any grade 4 thrombocytopenia and by 10% for a 1- to 2-week treatment delay for myelosuppression.


RESULTS
One of 19 patients who entered the study was ineligible. Eighteen patients received a median of 3.5 cycles (range: 1-6 cycles) of therapy. The overall RR was 27.8% (5.6% complete and 22.2% partial responses). Percent of patients with grade 3 or 4 toxicities included 78% neutropenia, 94% thrombocytopenia, 61% anemia, 44% GI, 28% infection, and 17% azotemia.


CONCLUSIONS
DMAP + sargramostim produced a 27.8% RR, but its complexity and toxicity precluded further investigation, and the study was closed after the first stage of accrual.
Long
Harry J
HJ
Department of Medical Oncology, Mayo Clinic College of Medicine, East 12B Mayo Building, 200 First Street, Southwest, Rochester, MN 55905-0001, USA. long.harry@mayo.edu
Blessing
John A
JA
Sorosky
Joel
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007890:Leiomyosarcoma / Q000188:drug therapy*; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D011994:Recombinant Proteins; D014594:Uterine Neoplasms / Q000188:drug therapy*
D011994:Recombinant Proteins; D016685:Mitomycin; C081222:sargramostim; D003606:Dacarbazine; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin