OBJECTIVE: To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) and MUC1 (PANVAC) would lengthen survival in patients with resected metastases of colorectal cancer (CRC). BACKGROUND: Recurrences after complete resections of metastatic CRC remain frequent. Immune responses to CRC are associated with fewer recurrences, suggesting a role for cancer vaccines as adjuvant therapy. Both DCs and poxvectors are potent stimulators of immune responses against cancer antigens. METHODS:Patients, disease-free after CRC metastasectomy and perioperative chemotherapy (n = 74), were randomized to injections of autologous DCs modified with PANVAC (DC/PANVAC) or PANVAC with per injection GM-CSF (granulocyte-macrophage colony-stimulating factor). Endpoints were recurrence-free survival overall survival, and rate of CEA-specific immune responses. Clinical outcome was compared with that of an unvaccinated, contemporary group of patients who had undergone CRC metastasectomy, received similar perioperative therapy, and would have otherwise been eligible for the study. RESULTS:Recurrence-free survival at 2 years was similar (47% and 55% for DC/PANVAC and PANVAC/GM-CSF, respectively) (χ P = 0.48). At a median follow-up of 35.7 months, there were 2 of 37 deaths in the DC/PANVAC arm and 5 of 37 deaths in the PANVAC/GM-CSF arm. The rate and magnitude of T-cell responses against CEA was statistically similar between study arms. As a group, vaccinated patients had superior survival compared with the contemporary unvaccinated group. CONCLUSIONS: Both DC and poxvector vaccines have similar activity. Survival was longer for vaccinated patients than for a contemporary unvaccinated group, suggesting that a randomized trial of poxvector vaccinations compared with standard follow-up after metastasectomy is warranted. (NCT00103142).
RCT Entities:
OBJECTIVE: To determine whether 1 of 2 vaccines based on dendritic cells (DCs) and poxvectors encoding CEA (carcinoembryonic antigen) and MUC1 (PANVAC) would lengthen survival in patients with resected metastases of colorectal cancer (CRC). BACKGROUND: Recurrences after complete resections of metastatic CRC remain frequent. Immune responses to CRC are associated with fewer recurrences, suggesting a role for cancer vaccines as adjuvant therapy. Both DCs and poxvectors are potent stimulators of immune responses against cancer antigens. METHODS:Patients, disease-free after CRC metastasectomy and perioperative chemotherapy (n = 74), were randomized to injections of autologous DCs modified with PANVAC (DC/PANVAC) or PANVAC with per injection GM-CSF (granulocyte-macrophage colony-stimulating factor). Endpoints were recurrence-free survival overall survival, and rate of CEA-specific immune responses. Clinical outcome was compared with that of an unvaccinated, contemporary group of patients who had undergone CRC metastasectomy, received similar perioperative therapy, and would have otherwise been eligible for the study. RESULTS: Recurrence-free survival at 2 years was similar (47% and 55% for DC/PANVAC and PANVAC/GM-CSF, respectively) (χ P = 0.48). At a median follow-up of 35.7 months, there were 2 of 37 deaths in the DC/PANVAC arm and 5 of 37 deaths in the PANVAC/GM-CSF arm. The rate and magnitude of T-cell responses against CEA was statistically similar between study arms. As a group, vaccinated patients had superior survival compared with the contemporary unvaccinated group. CONCLUSIONS: Both DC and poxvector vaccines have similar activity. Survival was longer for vaccinated patients than for a contemporary unvaccinated group, suggesting that a randomized trial of poxvector vaccinations compared with standard follow-up after metastasectomy is warranted. (NCT00103142).
Authors: D Schadendorf; S Ugurel; B Schuler-Thurner; F O Nestle; A Enk; E-B Bröcker; S Grabbe; W Rittgen; L Edler; A Sucker; C Zimpfer-Rechner; T Berger; J Kamarashev; G Burg; H Jonuleit; A Tüttenberg; J C Becker; P Keikavoussi; E Kämpgen; G Schuler Journal: Ann Oncol Date: 2006-01-17 Impact factor: 32.976
Authors: Timothy M Pawlik; Charles R Scoggins; Daria Zorzi; Eddie K Abdalla; Axel Andres; Cathy Eng; Steven A Curley; Evelyne M Loyer; Andrea Muratore; Gilles Mentha; Lorenzo Capussotti; Jean-Nicolas Vauthey Journal: Ann Surg Date: 2005-05 Impact factor: 12.969
Authors: Marcella Arru; Luca Aldrighetti; Renato Castoldi; Saverio Di Palo; Elena Orsenigo; Marco Stella; Carlo Pulitanò; Francesca Gavazzi; Gianfranco Ferla; Valerio Di Carlo; Carlo Staudacher Journal: World J Surg Date: 2008-01 Impact factor: 3.352
Authors: Mitchell C Posner; Donna Niedzwiecki; Alan P Venook; Donna R Hollis; Hedy L Kindler; Edward W Martin; Richard L Schilsky; Richard M Goldberg; Robert J Mayer Journal: Ann Surg Oncol Date: 2007-11-16 Impact factor: 5.344
Authors: Axel Andres; Pietro E Majno; Philippe Morel; Laura Rubbia-Brandt; Emiliano Giostra; Pascal Gervaz; Sylvain Terraz; Abdelkarim S Allal; Arnaud D Roth; Gilles Mentha Journal: Ann Surg Oncol Date: 2007-10-02 Impact factor: 5.344
Authors: Bernard Nordlinger; Halfdan Sorbye; Bengt Glimelius; Graeme J Poston; Peter M Schlag; Philippe Rougier; Wolf O Bechstein; John N Primrose; Euan T Walpole; Meg Finch-Jones; Daniel Jaeck; Darius Mirza; Rowan W Parks; Laurence Collette; Michel Praet; Ullrich Bethe; Eric Van Cutsem; Werner Scheithauer; Thomas Gruenberger Journal: Lancet Date: 2008-03-22 Impact factor: 79.321
Authors: Margaret E Gatti-Mays; Julius Strauss; Jeffrey Schlom; James L Gulley; Renee N Donahue; Claudia Palena; Jaydira Del Rivero; Jason M Redman; Ravi A Madan; Jennifer L Marté; Lisa M Cordes; Elizabeth Lamping; Alanvin Orpia; Andrea Burmeister; Eva Wagner; Cesar Pico Navarro; Christopher R Heery Journal: Clin Cancer Res Date: 2019-05-20 Impact factor: 12.531
Authors: Megan C Duggan; Caroline Jochems; Renee N Donahue; Jacob Richards; Volodymyr Karpa; Elizabeth Foust; Bonnie Paul; Taylor Brooks; Susheela Tridandapani; Thomas Olencki; Xueliang Pan; Gregory B Lesinski; Jeffrey Schlom; William E Carson Iii Journal: Cancer Immunol Immunother Date: 2016-08-31 Impact factor: 6.968
Authors: Benedetto Farsaci; Renee N Donahue; Italia Grenga; Lauren M Lepone; Peter S Kim; Brendan Dempsey; Janet C Siebert; Nuhad K Ibrahim; Ravi A Madan; Christopher R Heery; James L Gulley; Jeffrey Schlom Journal: Cancer Immunol Res Date: 2016-08-02 Impact factor: 11.151