English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Scientific progress is inhabited by paradigm shifts. In 1962, Tomas Kuhn popularized the concept of ¨paradigm shift¨ arguing that scientific advancement is not evolutionary, but rather is a "series of peaceful interludes punctuated by intellectually violent revolutions", and in those revolutions "one conceptual world view is replaced by another" (Kuhn, 1962). Again according to Kuhn, ¨paradigm shifts occur when anomalies in the old paradigm accumulate and cannot be overlooked anymore¨. This is probably the situation today in the treatment of advanced cancer. However, changes are difficult. Human beings resist changes. For many years, chemotherapy has been the gold standard of cancer therapy. The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs (De Vita et al, 2005) and a major break-through in 1965, when James Holland, Emil Freireich, and Emil Frei hypothesized that cancer chemotherapy should follow the strategy of antibiotic therapy for tuberculosis with combinations of drugs, each with different mechanisms of action (Frei et al, 1965). Cytotoxic chemotherapy in fact succeeded in producing major therapeutic effects, including cures, in hematological malignancies and some solid tumors such as testicular and ovarian cancers. However its contribution to the treatment of most solid tumors has been much less. The success history of chemotherapy in leukemia and lymphoma simply did not repeat in most solid tumors. Chemotherapy has the disadvantage of its high toxicity, because is an unspecific treatment which effect does not distinguish between normal and tumor cells. The paradigm of selective killing of cancer cells in a way alike to what antibiotics do for infections, created in turn a standardized procedure for stepwise drug development through conventional Phase I, II and III trials, which was soon adopted and translated into regulations by many drug regulatory authorities. The designs of these clinical trials respond to the need of demonstrating the drug efficacy at its maximal tolerable dose (MTD). However, although retaining the main concept and adapting to the old paradigm malfunctioning, variants have been introduced for cancer drugs approval: i.e. approvals without randomized trials and approvals based in accelerated approval regulations. From January 1973 through December 2006, 68 new drugs were approved for cancer therapy from which 31 were approved without 2 arms randomized clinical trials including a control arm with different therapy, supportive care or placebo (Tsimberidou, 2009).

Clinical Development Paradigms for Cancer Vaccines: The Case of CIMAvax EGF®