Download File - JOHN J. HADDAD, Ph.D.

46 Levey
patients. Although not the focus of this chapter, it is also clear that this very
setting is the most challenging in which to perform clinical trials. Patients with
early-stage disease live longer and, depending on the indication, will likely have
all visible disease completely resected. This leaves time to recurrence and overall
survival as the only reasonable markers of efficacy of subsequently administered
adjuvant immunotherapy. Although these are “gold standard” endpoints, trials in
this setting can easily extend beyond five years depending on the indication.
Despite this challenge, glimmers of success of autologous cancer vaccine
strategies have emerged and have grown more convincing during the last decade.
Looking forward, preclinical trends suggest that the tools exist to incrementally
extend active, personalized immunotherapy to later stages of disease. As is often
the practice in oncology, individual drugs that each address a distinct disease
pathway (e.g., anti-angiogenesis, immune suppression) will likely be used in
combination with therapeutic vaccines in this later stage. As this setting is relatively
more difficult to model due to the rapid rate of growth of rodent tumors,
it may prove necessary to look for evidence of additive or synergistic effects in
small clinical trials without the full complement of preclinical testing that is
more feasible in early stage disease.
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