A pilot study of bevacizumab (Bev) and continous low-dose granulocyte-macrophage colony-stimulating factor (GM-CSF) in heavily pretreated patients with refractory solid tumors: Preliminary results

Abstract

3031 Bev is an important inhibitor of VEGF, a mediator of tumor-induced angiogenesis. Inhibiting generation of dendritic cells (DC) from blood and tissue precursors, VEGF is also a crucial immunosuppressive agent in anti-tumoral immunotolerance. Beyond anti-angiogenesis, inhibition of VEGF may results in an improved antineoplastic immune response, which may be further improved by GM-CSF known to effectively stimulate DCs. GM-CSF has formerly be shown to induce objective responses in refractory gynecologic and breast carcinomas [Kurbacher et al. Oncology 2005]. This ongoing prospective clinical trial was initiated to investigate the combination of Bev and GM-CSF in patients (pts) with heavily pretreated solid tumors. Toxicity was documented according to the NCI-CTC scale, responses were recorded according to the RECIST or the Rustin criteria. Statistical pre-study considerations forced termination of the trial if no responses were observed among the first 12 pts recruited. Until now, 10 pts are included: epithelial ovarian carcinoma, n=4; metastatic breast cancer, n=3; peritoneal papillary-serous carcinoma, n=2; salivary gland adenocarcinoma, n=1. Regarding their history, all pts have been considered chemo-resistant or non-treatable due to their underlying bone marrow and/organ functions. Bev was applied at a fixed dose of 6 mg/kg q2w. GM-CSF was administered sc at 125 μg/d. GM-CSF was increased every 4 weeks at 25 μg/d increments until a maximum dose of 250 μg/d until occurence of objective tumor response or leukocytosis <20,000 cells/μL. Among the 10 pts treated so far, 2 partial responses (PR), 5 stable diseases (SD), and 3 progressive diseases (PD) have been recorded accounting for an objective response rate of 20%. Median time to progression is 16 weeks, with 7 pts still alive. Toxicity was generally mild and never therapy-limiting: NCI-CTC grade (G) 2 fatigue in 3 pts, G2 flu-like symptoms and G2 in either 1 pt, G1 injection site reactions in 3 pts. Preliminary results of this trial have shown Bev plus GM-CSF to produce a promising clinical activity in heavily pretreated pts with solid tumors. Thus, pts accrual is still continuing. No significant financial relationships to disclose.