Phase II trial of neoadjuvant docetaxel and CG1940/CG8711 followed by radical prostatectomy in patients with high-risk clinically localized prostate cancer.

BACKGROUND: Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP). METHODS: Patients received docetaxel administered at a dose of 75 mg/m(2) every 3 weeks for 4 cycles. GVAX was administered 2-3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10(8) cells. The subsequent boost immunotherapies consisted of 3×10(8) cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate. RESULTS: Six patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP. CONCLUSIONS: Neoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.

Venous and arterial thromboembolic complications associated with HIV infection and highly active antiretroviral therapy.

With the advent of highly active antiretroviral therapy (HAART), dramatic improvements have been made in the quality and length of life in people living with HIV/AIDS (PLWA). Complications that are seen with increasing frequency in this group include venous thromboembolism events (VTE) and cardiovascular disease. Recent epidemiologic studies suggest PLWA have a 2-fold to 10-fold greater risk of VTE compared with age-matched controls. Several mechanisms associated with HIV infection, coupled with traditional risk factors, including age, opportunistic infections, and lifestyle choices, may contribute to a heightened risk of VTE and cardiovascular disease. It has been challenging to discern which of these complications are related to HAART. Herein, we review the risk of VTE in the pre-HAART and current HAART era. We call attention to particular instances where components of HAART have been associated with acute myocardial infarction, noncirrhotic portal hypertension and portal vein thrombosis. We also highlight potential drug-drug interactions between HAART and anticoagulant therapy. Additional studies are needed to better understand the mechanisms and risks associated with long-term use of HAART and to what extent HAART contributes to or mitigates the risk of VTE and cardiovascular disease.