Phase II trial of GM-CSF in women with asymptomatic recurrent müllerian tumors.
OBJECTIVE
GM-CSF is a recombinant human cytokine, which promotes the proliferation and differentiation of granulocytes and monocytes, and is associated with anti-tumor activity. The primary objective was to define the median time to treatment termination (TTT) with women with relapsed ovarian cancer treated with single agent GM-CSF delivered subcutaneously (SC).


METHODS
Open label phase II study in asymptomatic patients with recurrent müllerian malignancy without an indication for immediate systemic chemotherapy. In the first cohort of 35 women, GM-CSF 250 microg/m(2) was administered SC on days 1-14 of a 28-day cycle, the second cohort received continuous GM-CSF 150 microg/m(2) given with dose escalation.


RESULTS
Seventy-two women were enrolled. Best overall response included one complete response, and 20 patients with stable disease (23%), 4 of whom had stable disease for >6 months. Median TTT was 78 days. Toxicity in both cohorts was generally mild; however, four patients experienced excessive toxicity and withdrew consent. In the first cohort, CA-125 dropped in 70% of women from their baseline on study value (median change -23%, range -48 to +116%) after 14 days of GM-CSF. The magnitude of CA-125 drop during the first 2 weeks of therapy also showed a positive inverse correlation with day 15 white cell count for the whole group (p=0.038).


CONCLUSIONS
GM-CSF is well tolerated and frequently associated with a decline in CA-125 that is correlated with leukocytosis. Although median TTT is modest, a subset of women had prolonged stable disease.
Roche
Maria R
MR
Dana-Farber/Harvard Cancer Center, representing members of the DF/HCC Gynecologic Oncology Research Group at Massachusetts General Hospital, and Dana-Farber Cancer Institute, Boston, MA, USA.
Rudd
Pandora J
PJ
Krasner
Carolyn N
CN
Matulonis
Ursula A
UA
Berlin
Suzanne T
ST
Lee
Hang
H
Silver
Michael
M
Tran
Chau D
CD
Seiden
Michael V
MV
Penson
Richard T
RT
D000328:Adult; D000368:Aged; D018394:CA-125 Antigen / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000097:blood / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy*
D018394:CA-125 Antigen; D016178:Granulocyte-Macrophage Colony-Stimulating Factor