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

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Summary

Batracylin (NSC 320846) is a water insoluble, solid tumor active compound discovered by the Developmental 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; > 950 zu∶C8), colon adenocarcinoma 9 (0–170 zu∶L1210; > 950 zu∶C9), colon adenocarcinoma 7/A (0–170 zu∶L1210; 250–400 zu∶C7), and pancreas ductal carcinoma 03 (0–170 zu∶L1210;>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 > 100%), colon #51 (T/C = 77%) and hepatoma 129 (T/C > 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 > 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.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Wayne State University School of Medicine, 48201, Detroit, Michigan, USA

    Patricia Mucci-LoRusso, Lisa Polin, Frederick Valeriote & Thomas H. Corbettv

  2. Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA

    Jacqueline Plowman

  3. Rhone-Poulenc Sante, Centre de Recherches de Vitry, Unite de Cancerologie Vitry sur Seine 94403, France

    Marie-Christine Bissery

  4. Division of Gastroenterology, Wayne State University School of Medicine, 48201, Detroit, Michigan, USA

    Gordon D. Luk

Authors
  1. Patricia Mucci-LoRusso
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  2. Lisa Polin
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  3. Marie-Christine Bissery
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  4. Frederick Valeriote
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  5. Jacqueline Plowman
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  6. Gordon D. Luk
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  7. Thomas H. Corbettv
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Mucci-LoRusso, P., Polin, L., Bissery, MC. et al. Activity of batracylin (NSC-320846) against solid tumors of mice. Invest New Drugs 7, 295–306 (1989). https://doi.org/10.1007/BF00173759

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