Clinical drug development: an analysis of phase II trials, 1970-1985

Area of Science:

• Oncology
• Clinical Pharmacology
• Drug Development

Background:

• Cytotoxic drugs are a cornerstone of cancer chemotherapy.
• The National Cancer Institute (NCI) has developed numerous cytotoxic agents since 1970.
• Evaluating drug activity in early-phase clinical trials is crucial for drug development.

Purpose of the Study:

• To assess the efficacy of cytotoxic drugs developed by the NCI in Phase II clinical trials.
• To identify cancer types most responsive to NCI-developed cytotoxic drugs.
• To evaluate the completeness of clinical testing for these drugs.

Main Methods:

• Systematic review of Phase II trial data for NCI-developed cytotoxic drugs introduced since 1970.
• Calculation of response rates from pooled data, with drugs rated active if the lower 80% confidence bound exceeded 10%.
• Assessment of clinical testing completeness based on patient numbers and tumor types evaluated.

Main Results:

• Of 83 NCI-developed drugs, 47 were evaluable, with 24 showing activity in at least one cancer type.
• Lymphoma (74%), leukemia (35%), and urothelial cancer (29%) demonstrated the highest drug activity rates.
• Testing completeness varied significantly across cancer types; breast, colon, and non-small cell lung cancer had more extensive evaluations.

Conclusions:

• A significant proportion of NCI-developed cytotoxic drugs demonstrate activity in specific cancer types.
• Phase II trial design should prioritize minimum accrual, patient populations with minimal prior therapy, and evaluation across a defined set of tumor types.
• Optimizing Phase II trial strategies can improve the identification of effective cytotoxic agents for cancer treatment.