Bevacizumab and granulocyte-macrophage colony-stimulating factor in pretreated patients with metastatic solid malignancies

Bevacizumab (BEV) is an important anti-angiogenetic agent which may also stimulate the generation of dendritic cells (DC). This effect may be further potentiated by GM-CSF. This trial was initiated to study BEV+GM-CSF in 21 patients (pts) with metastatic solid malignancies: ovarian cancer, n=8; breast cancer, n=5; primary peritoneal carcinoma, n=3; hormone-refractory prostate cancer, n=2; others, n=3. All pts have been considered refractory to chemotherapy or non-treatable due to their baseline bone marrow and/or organ functions. Eight patients had previously received BEV as part of other anti-neoplastic regimens. BEV was applied at a fixed dose of 6mg/kg q2w. GM-CSF (sargramostim) was administered SC at 125µg/d. GM-CSF was increased every 2 weeks at 25µg/d increments up to a maximum of 250µg/d if no objective tumor response or moderate leukocytosis ( < 20,000 cell/µL) was achieved. Adverse effects were scored according to the NCI-CTC scale, responses were recorded according to the RECIST or Rustin criteria. Treatment was generally well tolerated: grade (G) 3–4 toxicities were hypertension and fatigue in either 2 pts, and fever, pain, and flu-like symptoms in either one pt. One CR, 7 PR, 8 SD, and 5 PD accounted for an objective response rate of 38%. The rate of pts benefiting was 71%. Most interestingly, all 8 pts previously failing BEV benefited from BEV+GM-CSF. Until today, 9 pts have died while 5 pts are still progression-free. The median time to progression is 99 days and the median survival is 406 days. The results of this pilot trial argue in favor that BEV+GM-CSF is an active and well tolerated therapy in mainly heavily pretreated pts with solid tumors.