Present research in the chemotherapy of malignant disease has followed two general patterns. The first and most extensively pursued has been attempts to discover new and better therapeutic agents. The second approach has been attempts to develop methods of increasing the therapeutic effectiveness of the presently available agents by trying to decrease their systemic toxicity or to increase their therapeutic ratio. Mechlorethamine (nitrogen mustard), the oldest of the present day chemotherapeutic agents, has been the most intensively studied with this latter objective in mind.Klopp1 first demonstrated an increase in therapeutic effect and at the same time a decrease in systemic toxicity of mechlorethamine when it was administered by the intra-arterial rather than the intravenous route. This was almost simultaneously confirmed by Bierman et al.2 Several recent investigators have reported attempts to reduce the systemic toxicity of mechlorethamine by the simultaneous infusion of cysteine or thiosulfate solutions.
MARSHALL WH, HOPPE ET, STARK F. The Effect of Ambient Oxygen Tension on the Toxicity and Therapeutic Effect of Mechlorethamine (Nitrogen Mustard). Arch Surg. 1963;86(6):932–939. doi:https://doi.org/10.1001/archsurg.1963.01310120050009
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