Phase II trial of dacarbazine, mitomycin, doxorubicin, and cisplatin with sargramostim in uterine leiomyosarcoma: a Gynecologic Oncology Group study.

Abstract

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.

• Authors: Harry J Long 3rd, John A Blessing, Joel Sorosky
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 99 Issue 2 Pg. 339-42 (Nov 2005) ISSN: 0090-8258 [Print] United States
• PMID: 16051328 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• Recombinant Proteins
• Mitomycin
• sargramostim
• Dacarbazine
• Doxorubicin
• Granulocyte-Macrophage Colony-Stimulating Factor
• Cisplatin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Cisplatin (administration & dosage, adverse effects)
• Dacarbazine (administration & dosage, adverse effects)
• Doxorubicin (administration & dosage, adverse effects)
• Drug Administration Schedule
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (administration & dosage, adverse effects)
• Humans
• Leiomyosarcoma (drug therapy)
• Leukopenia (chemically induced)
• Middle Aged
• Mitomycin (administration & dosage, adverse effects)
• Recombinant Proteins
• Uterine Neoplasms (drug therapy)