Bis-diketopiperazine derivatives in clinical oncology: ICRF-159

ICRF-159 is a bis-diketopiperazine derivative active in a variety of preclinical animal tumor models. Because of its poor solubility characteristics, the drug must be given p.o. However, when given by this route at high doses, poor bioavailability was noted. Two interesting preclinical properties of this agent are its antimetastatic effect and the ability to reduce anthracycline cardiotoxicity. Phase I studies have delineated myelosuppression as the major toxicity with GI toxicity also occurring. In phase II studies, interesting activity has been noted in lymphomas and head and neck carcinomas. When ICRF-159 was combined with radiotherapy, prolonged responses were noted in sarcoma and lung carcinoma in small numbers of patients. Further studies are indicated in areas of activity as a single agent and as a potentiator of radiation therapy.