A phase II study of active immunotherapy with PANVAC or autologous, cultured dendritic cells infected with PANVAC after complete resection of hepatic metastases of colorectal carcinoma.

Rationale Although metastatic colon cancer is frequently incurable, large studies have confirmed a 25%-30% 5-year survival rate after complete resection of hepatic metastases.1-3 Unfortunately, intraand extrahepatic recurrences are still observed in two thirds of patients after resection of liver metastases. The most effective way to reduce hepatic recurrences that has been reported in randomized studies thus far is to use the combination of hepatic arterial infusion (HAI) and systemic chemotherapy postoperatively. Although Lorenz et al tested HAI with 5-fluorouracil (5-FU) and folinic acid without systemic treatment and showed no benefit over surgery alone,4 Kemeny et al from the Memorial SloanKettering Cancer Center compared HAI of floxuridine plus systemic 5-FU and folinic acid with systemic 5-FU and folinic acid alone after surgery and reported that the combined treatment resulted in a decrease in the hepatic recurrence rate and an improved overall survival but only at 2 years.5 More recently, Kemeny et al reported that HAI with floxuridine combined with intravenous, continuous-infusion 5-FU reduced the risk of recurrence when compared with surgery alone but resulted in no benefit in overall survival.6 Therefore, it has been suggested that surgery plus chemotherapy might reduce the risk of recurrences after surgery for liver metastases7 but that further therapies are clearly needed. Immunotherapy represents a non–cross reactive and potentially less toxic method for improving outcome. Colorectal cancers represent a reasonable target for vaccines because they are known to express tumor-associated and tumor-specific antigens (carcinoembryonic antigen [CEA], melanoma antigen gene family, MUC-1, p53, and others), and T cells specific for these antigens can be detected in the peripheral blood of some patients with colon cancer.8 Colon cancer vaccines have reached phase II/III testing, and trends toward clinical benefit have been reported in patients developing an immune response.9,10 Nonetheless, better vaccine strategies are required in order to improve the immune response against tumor antigens and to improve the clincial activity when the immune response has been activated. Numerous approaches to inducing immune responses against colon cancer have been attempted, including immunization with autologous tumor viral vectors encoding tumor antigens such as CEA, peptides, and dendritic cell–based vaccines.11 Recently, recombinant pox vectors, including vaccinia (rV)– and fowlpox (rF)–encoding CEA have been tested in patients with advanced-stage colon cancers. An intriguing observation was that the group of patients who received the prime boost strategy of rV-encoding CEA followed by rF-encoding CEA had greater CEA-specific T-cell responses and prolonged survival compared with those who received the reverse order of administration. This Submitted: Nov 28, 2005; Accepted: Jan 11, 2006 1Department of Medicine, Duke University Medical Center 2Medical Oncology, Georgetown, Lombardi Cancer Center, Washington, DC 3Medical Oncology, Wake Forest-Baptist Medical Center, WinstonSalem, NC 4Surgical Oncology, Medical University of South Carolina, Charleston 5Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston Emil Lou,1 John Marshall,2 Mebea Aklilu,3 David Cole,4 David Chang,5 Michael Morse1