A pilot study with ethyl bis (2,2-dimethyl-1-aziridinyl) phosphinate (AB-163) and radiation therapy.
Ethyl bis (2,2 dimethyl-1-aziridinyl) phosphinate (AB-163), a TEPA analogue, was used with radiation therapy in treating 18 patients with advanced malignancies. There were 12 patients with esophageal carcinoma; 3 with adenocarcinomas of the gastrointestinal tract; one, squamous carcinoma of the cervix; and one, adenocarcinoma of the ovary. One hundred mg/M2 AB-163 was given by rapid i.v. drip one half-hour before conventional radiation therapy. The majority of patients received 10 combined treatments. Three of those with squamous cell carcinomas (two in the esophagus and one in the cervix) remained disease-free for more than 2 years. One with liver metastasis and unresectable carcinoma of the stomach survived for 9 months. The drug causes side effects mainly involving the central nervous system and gastrointestinal tract. Drug-related myelosuppression has not been observed. The mode of action is speculated to be a result of active intermediate hydrolysis products which appear capable of phosphorylating X ray induced DNA strand damage. However, much additional investigation is required, both in vitro and clinically, before its efficacy and safety can be demonstrated.
D000230:Adenocarcinoma / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D001388:Aziridines / Q000009:adverse effects / Q000494:pharmacology*; D001389:Azirines / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy; D004341:Drug Evaluation; D004938:Esophageal Neoplasms / Q000532:radiotherapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000532:radiotherapy*; D010051:Ovarian Neoplasms / Q000532:radiotherapy; D010190:Pancreatic Neoplasms / Q000532:radiotherapy; D010865:Pilot Projects; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000494:pharmacology*; D011882:Radiotherapy, High-Energy; D013274:Stomach Neoplasms / Q000532:radiotherapy; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy
D001388:Aziridines; D001389:Azirines; D011838:Radiation-Sensitizing Agents; C001181:AB 163