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.
Mucci-LoRusso
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Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.
Polin
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Bissery
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Valeriote
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Plowman
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Luk
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Corbett
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D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000188:drug therapy; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011799:Quinazolines; C057924:batracylin