The indicate age at inclusion was 46. eight years. Patient no characteristics are listed in Table 1. Of the 21 included sufferers, one patient died of progressive disease just before get started of your vaccinations. Eleven pa tients completed all 4 vaccinations. Five sufferers obtained 3 vaccinations, and four individuals received two vaccinations. Safety and tolerability Tumor progression was the main reason for early ter mination within the research. All patient deaths occurred due to progressive disease. One particular patient stopped just after 3 vacci nations due to the fact of persisting flu like signs and swelling of vaccination web sites. All round, the vaccine was nicely tolerated. None with the systemic and local ad verse events exceeded CTCAE grade 2. The vaccination was accompanied mostly with erythema and swelling of your skin.
Hematological values assessed inside the blood samples drawn prior to and immediately after vaccination did not present major alterations. Tumor response and survival The final follow up was performed in December 2011. In eleven on the twenty vaccinated patients target lesions have been identi fied and measured just before and immediately after vaccination. In 8 individuals submit vaccination scans were not manufactured be result in of refusal to undergo radiological examinations or since of clinically progressive condition or death. In 3 individuals, the target lesions displayed stable dis ease while the target lesions of all other 8 sufferers were classified as progressive sickness. In 12 in the vaccinated individuals non target lesions might be evaluated. The general tumor response in all 12 sufferers in whom a response may be assessed, was progressive ailment.
Following immunotherapy, three individuals were handled with che motherapy only, two patient with chemo radiation therapy and 1 patient with radiotherapy only. In December 2011, the median overall survival of your vaccinated group was 12. six months after diagnosis of recurrence and 27. 3 months after main diagnosis. Recalculation of the survival for the sixteen vaccinated individuals with HPV16 induced cervical carcinoma exposed a median general sur vival of eight. eight months after diagnosis of recurrence and 24. 5 months just after primary diagnosis. One particular patient was alive in a clinically great issue at 19. four months just after 4 vaccinations, she came back with progressive condition in Might 2012 but was even now alive in October 2012.
Immune responses Blood samples were isolated from 20 sufferers prior to vac cination and from 15 patients just after the 2nd vaccin ation, from eleven of whom blood was also isolated immediately after both the third or fourth vaccination. In 9 sufferers a vaccine induced HPV16 certain proliferative response right after the second and/or last vaccination was discovered. A significant enhance from the power of proliferation was mentioned after either 2 vaccinations and just after three to four vacci nations in contrast to base line values. In addition, the power of your response increased amongst two vaccine doses along with the last vac cination.