Activity of batracylin (NSC-320846) against solid tumors of mice.

Batracylin (NSC 320846) is a water insoluble, solid tumor active compound discovered by the Development Therapeutics Program of the National Cancer Institute (NCI). In vivo, the NCI found this compound to be highly active [median treated tumor mass/median control tumor mass (T/C) = 0 to 20%] both orally and intraperitoneally against colon 38. In a disk diffusion, soft agar colony formation assay (500 ug/disk), we found solid tumor selectively (compared to leukemia L1210) against colon adenocarcinoma 38 (0-170 zu:L1210 leukemia; greater than 950 zu:C8), colon adenocarcinoma 9 (0-170 zu:L1210; greater than 950 zu:C9), colon adenocarcinoma 7/A (0-170 zu:L1210; 250-400 zu:C7), and pancreas ductal carcinoma 03 (0-170 zu:L1210; greater than 950 zu:Panc 03 (200 zone units [zu] = 6.5 mm zone of inhibition of cultured tumor colonies from drug disk). In vivo we have tested batracylin against mammary adenocarcinoma 16/C, colon 9, colon 38, colon 51, Panc 03, and hepatoma 129. Upon oral administration, batracylin was effective against colon 9 (T/C = 2.4%) and marginally active against colon 38 (T/C = 39%). Batracylin was orally ineffective against Panc 03 (T/C greater than 100%), colon #51 (T/C = 77%) and hepatoma 129 (T/C greater than 100%). Upon subcutaneous administration, batracylin was effective against colon #9 (T/C = 0%), and Panc 03 (T/C = 15%) but ineffective against mammary 16/C (T/C greater than 100%). At efficacious doses, delayed neurotoxicity, hepatic toxicity and a significant host weight loss was noted (with slow recovery). Both our in vitro data and the NCI in vivo data confirm its scant activity against L1210 (%ILS = 8 to 16%). Although showing activity against selected murine solid tumors, it lacked curative potential with early stage disease [C38, C9, Panc 03] and has shown relative inactivity in vitro against human solid tumor cell lines (H-125, CX-1, HCT-8, HCT-116). Batracylin has entered large animal toxicology trials at the NCI, anticipating phase I clinical evaluation.