Objective: Vascular endothelial growth factor (VEGF) is a glycoprotein that is important in promoting tumor angiogenesis. Recombinant humanized anti (rhuMAb)-VEGF is a humanized murine monoclonal antibody that neutralizes VEGF activity and has shown promise in animal tumor models. Methods: To evaluate the efficacy and safety of single-agent rhuMAb VEGF in metastatic androgen-independent prostate cancer (AIPC), we treated 15 patients with 10 mg/kg rhuMAb VEGF every 14 days for six infusions (one cycle), followed by additional treatment for selected patients who had a response or were stable. Results: After one cycle, none of the 15 patients who were evaluable for tumor response had an objective complete or partial response. Three possible mixed responses were observed. No patient achieved a >50% decrease in serum prostate specific antigen (PSA) level after one cycle. Four patients (27%) had a PSA decline of <50%, three patients (20%) had a PSA level increase of <50%, and eight patients (53%) had a PSA increase of >50%. The median time to objective progression was 118 days, and the median time to PSA progression was 57 days. Toxicity was generally mild, with asthenia present in 6 (40%) of 15 patients. Severe hyponatremia developed in two patients, although the association with rhuMAb VEGF was unclear. Conclusions: We concluded that single-agent rhuMAb VEGF in this dose and with this schedule did not produce significant objective responses in patients with AIPC. Further development of this agent in patients with prostate cancer should focus on earlier stage disease or should evaluate it in combination with other therapies.

BACKGROUND The treatment of patients with metastatic renal cell carcinoma (RCC) continues to pose a major clinical challenge. Previous studies have suggested that infusional floxuridine (FUDR) has antitumor efficacy and is well tolerated. To the authors knowledge the combination of infusional FUDR with biologic response modifiers (BRMs) has not been evaluated extensively in patients with metastatic RCC. METHODS Thirty‐nine previously untreated patients with metastatic RCC were treated with infusional FUDR at 0.075 mg/kg/day for 14 days of a 28‐day cycle. Beginning with the second cycle of FUDR, 24 patients received subcutaneous interferon‐α‐2b (3 million U 3 times a week for Weeks 1 and 2) and 15 received subcutaneous interleukin‐2 (IL‐2) (5 million U/m2 5 days a week for 3 weeks, followed by 1 week off). The dose of FUDR was increased by 0.025 mg/kg each cycle until the maximum tolerated dose for each patient was reached. RESULTS Five patients receiving FUDR plus interferon achieved a partial response and 1 achieved a complete response whereas 3 patients receiving FUDR plus IL‐2 achieved a partial response, for an overall response rate of 23%. The median survival for all patients was 21 months, and 8 patients still were alive 6–57+ months after the initiation of therapy. Toxicity was mild to moderate, and was comprised primarily of fatigue, diarrhea, dacryocystitis, and fluid retention (in the IL‐2 cohort). CONCLUSIONS FUDR in conjunction with IL‐2 or interferon appears to produce response rates comparable to those observed with other programs utilizing BRMs and generally is well tolerated. FUDR regimens may be useful in the treatment of metastatic RCC in the outpatient community setting. Cancer 2000;88:1310–6. © 2000 American Cancer Society.

FUDR in conjunction with IL-2 or interferon appears to produce response rates comparable to those observed with other programs utilizing BRMs and generally is well tolerated. FUDR regimens may be useful in the treatment of metastatic RCC in the outpatient community setting.