RESPONSES AND TOXIC DEATHS IN PHASE-I CLINICAL-TRIALS

This review analysis consists of the antitumor activity and toxic deaths reported in single agent Phase I clinical trials using cytotoxic compounds published from 1972 to 1987. A total of 6639 patients with a variety of solid tumors and hematological malignancies were accrued in 211 trials studying 87 compounds. The median number of patients per trial was 28 (range: 7-111) and the median of the median ages reported in the individual trial was 56 (range of individual age: 2 to 93 years). Ten percent of the trials enrolled pediatric patients (< 18 years), but the exact numbers of children were not always given or separated from the adult patients. Nine percent of the patients had received no prior treatment, 75% were pretreated either with chemotherapy alone (50%) or radio- plus chemotherapy (25%). Radiotherapy alone was adminis-tered to 11% of the patients and the remaining 5% of the patients received prior treatments which was not specified. The most frequent tumor types were those of the gastrointestinal tract (22%) and the respiratory tract (19%). The frequency of the remaining malignancies was < 10% of all patients. There were 23 (0.3%) complete responders and 279 (4.2%) partial responders for an overall response rate of 4.5% among all entries. Toxic deaths were rare and reported in only 31 patients (0.5% of the entire population). Responses were usually observed in chemosensitive tumor types. Despite a low response rate reported during the first phase of cytotoxic drug development, the present analysis shows that some therapeutic benefit can be achieved. © 1990 Kluwer Academic Publishers.