A Methylhydrazine Derivative in Hodgkin's Disease and Other Malignant Neoplasms

doi:10.1059/0003-4819-63-1-69

A Methylhydrazine Derivative in Hodgkin's Disease and Other Malignant Neoplasms

Therapeutic and Toxic Effects Studied in 51 Patients

KURT W. BRUNNER, M.D.; and
CHARLES W. YOUNG, M.D.

Requests for reprints should be addressed to Charles W. Young, M.D., Sloan-Kettering Institute,
410 East 68th St., New York, N. Y. 10021
.

Excerpt

Methylhydrazine derivatives form a new class of synthetic cytotoxic compounds. They possess antineoplastic activity in animal tumor systems (1, 2) and in patients with malignant lymphoma (3, 4). The most widely studied of these derivatives is N-isopropyl-alpha-(2-methylhydrazino)-ρ-toluamide hydrochloride, (Ro 4-6467, NSC-77213) (Figure 1).* It is reported to have teratogenic (5), immunosuppressive (6), and carcinogenic properties (7) in addition to antineoplastic activity.

The molecular mechanism by which methylhydrazine derivatives produce biological effects is unknown. Observations in noncellular systems have disclosed that methylhydrazine is autoxidized in oxygen-containing aqueous solution with formation of hydrogen peroxide and oxygen-hydrogen radicals. These, in turn, degrade deoxyribonucleic

Acknowledgments

The authors acknowledge the support and advice of Dr. David A. Karnofsky throughout the course of this study and the preparation of the manuscript. We express our appreciation to Drs. James J. Fennelly, Pierre Gibert, and Martin Weiner for assistance in the clinical care of patients in this series and thank Dr. William Geller and other physicians of the Medical Oncology Service for their interest and for the referral of patients to this study. Finally, we thank Dr. Edward Miller and the Hoffman-La Roche Co., Nutley, N. J. for their efforts in assuring an adequate supply of NSC-77213 for clinical use.

Summario in Interlingua

Hydrochloruro de N-isopropyl-α-(2-methyl-hydrazino)-ρ-toluamida esseva administrate a 51 adultos con avantiate morbo neoplastic. In 38 le administration del pharmaco representavaun adequate essayo therapeutic. Grados significative de regression del massa tumoral e melioration clinic de duration de plus que un mense esseva constatate in 12 de 20 patientes con morbo de Hodgkin, 1 de 2 patientes con lymphosarcoma, e 1 de 4 patientes con sarcoma a cellulas reticular. Le manifestationes toxic del pharmacotherapia includeva nausea, vomito, e depression del medulla ossee e del systema nervose central. In patientes con morbo de Hodgkin, le sequente programma therapeutic pareva esser le optime: 20 a 30 mg/kg/septimana (circa 200 a 300 mg/die) durante 3 septimanas, postea 5 mg/kg/septimana (50 mg/die) si tolerate como dosage de mantenentia. Le pharmaco esseva administrate per via oral in dividite doses diurne. Illo esseva le plus efficace in patientes con morbo de Hodgkin qui se trovava in stato de compensation clinic e qui habeva recipite nulle extense hemotherapia in tempores anterior. Tamen, interessante responsas de un duration de plus que un mense esseva obtenite in 6 de 12 patientes le quales habeva previemente recipite agentes alcoylante e alcaloides Vinca usque al establimento de tolerantia sin que le activitate del morbo permaneva sub dominio.

Iste derivato de methylhydrazina es clinicamente util in le tractamento de morbo de Hodgkin. Le datos currentemente disponibile non permitte le formulation de conclusiones relative al valor o al indicationes del agente in comparation con alcoylante e/o alcaloides Vinca.

Article and Author Information

From the Medical Oncology Service, Department of Medicine, Memorial Hospital and James Ewing Hospital, and Division of Clinical Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, N. Y.
This research was supported in part by grants CA-03215 and CA-5826 from the National Cancer Institute, U. S. Public Health Service, Bethesda, Md.
↵* At present this is the only methylhydrazine derivative that has been extensively studied in patients; accordingly, we use the term methylhydrazine throughout this report to refer to Ro 4-6467 (NSC-77213).
- Received December 28, 1964.
- Accepted February 4, 1965.