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Studies in a Tumor Spectrum

III. The Effect of Phosphoramides on the Growth of a Variety of Mouse and Rat Tumors^*

( Laboratories of the Sloan-Kettering Division of Cornell University Medical College in the Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, N.Y.)

1. The effects of diethylene phosphoramide (DEPA), triethylene phosphoramide (TEPA), and triethylene thiophosphoramide (TSPA) have been tested against a spectrum of eighteen tumors of the mouse, five tumors of the rat, and three ascites tumors of the mouse.

2. Daily maximum tolerated doses of 6 mg/kg of TEPA in mice had a destructive effect on Carcinoma 1025, Ridgway osteogenic sarcoma, and Andervont hepatoma; a marked inhibitory effect on Miyono adenocarcinoma and Gardner lymphosarcoma; a moderate inhibitory effect on Sarcoma 180, Adenocarcinoma E 0771, Ehrlich carcinoma, Grand epidermoid carcinoma, Wagner osteogenic sarcoma, Lewis bladder carcinoma, and Lewis lung carcinoma; a slight inhibitory effect on Sarcoma MA 387, Bashford carcinoma 63, and Harding-Passey melanoma, but no effect on Sarcoma T 241.

3. Daily maximum tolerated doses of 4 mg/kg of TSPA in mice had a destructive effect on Carcinoma 1025, Ridgway osteogenic sarcoma, Gardner lymphosarcoma, and Andervont hepatoma; a marked inhibitory effect on Adenocarcinoma E 0771 and Bashford carcinoma 63; a moderate inhibitory effect on Sarcoma 180, Miyono adenocarcinoma, Ehrlich carcinoma, Grand epidermoid carcinoma, Wagner osteogenic sarcoma, Harding-Passey melanoma, Lewis bladder carcinoma, and Lewis lung carcinoma, and a slight inhibitory effect on Sarcoma T 241, Sarcoma MA 387, Patterson lymphosarcoma, and Mecca lymphosarcoma.

4. The effects of TEPA and TSPA on these eighteen mouse tumors were generally similar, and these compounds were far more effective than DEPA.

5. Both TEPA and TSPA had a marked inhibitory effect upon the development of Ehrlich ascites carcinoma and Krebs 2 ascites carcinoma, but only a slight inhibitory effect on Sarcoma 180 ascites tumor. DEPA had relatively no effect on these three ascites tumors.

6. The growth of spontaneous mammary adenocarcinomas in Swiss albino mice was stopped by repeated injections of TSPA, but there was no significant increase in complete tumor regression over the controls.

7. Daily doses of 1 mg/kg of DEPA, 1 mg/kg of TEPA, and 2 mg/kg of TSPA in rats had a destructive effect on 1-day-old implants of Flexner-Jobling carcinoma, Walker carcinosarcoma 256, Sarcoma R 39, and Jensen sarcoma, but no effect on Murphy-Sturm lymphosarcoma.

8. Complete regression was obtained in large numbers of certain well established 7-day-old mouse and rat tumors by administration of seven daily doses of DEPA, TEPA, and TSPA. For rats, daily doses of 1-2.5 mg/kg of DEPA gave 80 per cent regressions for Flexner-Jobling carcinoma, 65 per cent for Sarcoma R 39, and 80 per cent for Jensen sarcoma. For mice, daily doses of 6 mg/kg of TEPA gave 82 per cent regressions for Carcinoma 1025, 83 per cent for Ridgway osteogenic sarcoma, and 80 per cent for Gardner lymphosarcoma. Similarly, for rats, daily doses of 1 mg/kg of TEPA gave 73 per cent regressions for Flexner-Jobling carcinoma, 93 per cent for Sarcoma R 39, and 75 per cent for Jensen sarcoma. Similarly, for mice, daily doses of 4 mg/kg of TSPA gave 83 per cent regressions for Carcinoma 1025, 78 per cent for Ridgway osteogenic sarcoma, and 70 per cent for Gardner lymphosarcoma. For rats, daily doses of 2 mg/kg gave 80 per cent regressions for Flexner-Jobling carcinoma, 60 per cent for Walker carcinosarcoma 256, and 86 per cent for Jensen sarcoma.

^* This study was supported by an institutional grant to the Sloan-Kettering Institute from the American Cancer Society and by a grant from the Damon Runyon Memorial Fund for Cancer Research.

Received 8/ 3/54.

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