Two phase I studies of prime-boost vaccinations with vaccinia-fowlpox vaccines expressing CEA, MUC-1, and TRICOM costimulatory molecules (B7.1/ICAM-1/LFA-3) in patients with advanced pancreatic cancer
2004; Lippincott Williams & Wilkins; Volume: 22; Issue: 14_suppl Linguagem: Inglês
10.1200/jco.2004.22.90140.2564
ISSN1527-7755
AutoresThomas Schuetz, John Marshall, Howard L. Kaufman, Howard Safran, Dennis Panicali,
Tópico(s)Cancer Research and Treatments
Resumo2564 Background: Recombinant pox viruses have been developed as therapeutic anti-tumor vaccines. Previous studies have demonstrated a correlation between the generation of T-cell immunity by these vaccines and overall survival (OS). We report the results of two Phase I studies of vaccines targeting MUC-1 and CEA. Methods: The first study tested an earlier generation of the vaccines. The second study tested recombinant vaccinia and fowlpox viruses co-expressing CEA, MUC-1, and the TRICOM genes (PANVAC-VF). Safety was the primary objective of both studies. Twenty-two patients with advanced pancreatic cancer (Stage III or IV) were enrolled (20 with metastatic disease; all had received prior therapy). Patients received a ‘prime’ dose of vaccinia on Day 0, followed by ‘boost’ doses of fowlpox on Days 14, 28, and 42; all vaccinations were followed by local GM-CSF (100 μg) for 4 days. Patients who were clinically stable were able to continue vaccinations monthly. Safety parameters evaluated included vital signs, physical examination, laboratory tests, and adverse events (AEs). All patients were followed for survival. Results: The most common AE related to the vaccines was grade 1 injection site reaction, which included erythema, swelling, pruritis, blister, induration, and pain. Other common AEs were fatigue, anorexia, nausea, vomiting, fever, headache, and myalgia. There was one grade 3 fever. No serious adverse events related to vaccine occurred. Six of the 12 patients enrolled in the first study have died. However, the median OS cannot yet be calculated and currently is at least 7.3 months. Conclusions: All of the patients in the first study had metastatic disease at baseline and all had failed first-line chemotherapy. Historical control data suggest that the expected median OS in this patient population is approximately 3 months. Although the sample size is small and the analysis is limited by comparison to historical controls, these data suggest that vaccination has improved median OS in this patient population. A randomized trial is planned for early 2004. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Therion Biologics Roche; Therion Biolgoics Therion Biolgoics
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