A pilot trial of chronic low-dosegranulocyte-macrophage colony-stimulating factor therapy in patients with intensively pretreated breast or female genital tract cancer

Abstract

2537 Background: Prolonged low-dose (PLD) granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment which stimulates dendritic cell differentiation has been successfully used in patients (pts) with stage III-IV melanoma. However, data of PLD GM-CSF therapy in other tumors are still lacking. This pilot trial was thus initiated in order to evaluate both the efficacy and tolerabilty of PLD GM-CSF in pts with various heavily pretreated solid malignancies. Methods: 16 pts failing 2–7 prior (median, 4) chemotherapies were included with: metastatic breast cancer (MBC), n=6; recurrent ovarian carcinoma (ROC), n=8; metastatic endometrial carcinoma (MEC), n=1; recurrent cervical cancer (RCC, n=1). PLD GM-CSF (Leukine®) was delivered subcutaneously at a daily starting dose of 125 μg. The treatment was monitored by weekly whole blood cell counts (WBC). GM-CSF was increased at 25 μg increments until a maximum of 200 μg or when mild leukocytosis (i. e. 10–20 G/l) was achieved. Therapy was continued until progression or refusal by the pts. Response was assessed using either the common ECOG score (in 13 pts with measurable disease) or the Rustin criteria for CA 125-positive ROC (n=3). Results: All pts are evaluable for toxicity which was generally mild. In 2 pts, temporary dose-reduction was necessary due to mild skin reactions, which recovered spontaneously. Mild to moderate leucytosis was obvious in 7 pts. Hypersensitivity-like reactions did not occur nor did any pt require hospitalization to other life-threatening side effects. The objective response rate was 38% with 1 CR, 5 PR, 3 SD, and 7 PD. Response-duration ranged between 2 and 13 months, respectively. Until today, 8 pts are still alive. Notably, 5 of 6 responders but only 1 of 7 pts with PD developed leukocytosis during therapy. Conclusion: PLD GM-CSF exhibits substantial activity in heavily pretreated patients with either MBC or female genital tract cancer with mild leukocytosis being a potential predictor of response. Large-scaled clinical trials are now warranted to define the exact clinical value of this promising new strategy. No significant financial relationships to disclose.