Sometimes noteworthy toxic events occur. These are very carefully documented and promptly treated. The increases in the dosage are interrupted and further study at the highest safe level is conducted. Researchers also study what happens to the drug in the body (drug metabolism and pharmacology).
What provides the "green light" to proceed to Phase II is the discovery of a dose level that causes only mild or manageable toxicities but also produces drug concentrations in the blood that are in the range for antitumor effects found in preclinical experiments. It is even more encouraging if patients are seen to benefit even when some received doses later found to be too low or when most have tumors that resist treatment.
Phase II For a more accurate assessment of potential, the drug in this phase is tested for effectiveness in small groups of patients with specific types of cancer. The objective of Phase II trials is to determine if the new agent can cause major shrinkage of tumors (objective response). Taxol , for example—which was in short supply— was advanced to three Phase II studies involving women with ovarian cancer that had resisted the established drug cisplatin . This was done to confirm the substantial improvements seen in patients with this disease during the Phase I trials.
Phase III This begins when a drug has proved to be effective in Phase II. A randomized study is usually necessary to make the drug part of the standard treatment strategy. In a randomized study, half the patients receive the best standard therapy and the other half the new therapy.
