New protective agents for bone marrow in cancer therapy.
WR-2721 is a unique bone marrow protective agent which also protects other normal tissues against the toxic effects of radiation therapy and chemotherapy, especially with cisplatin and alkylating agents. In addition to protection against acute toxicities, WR-2721 has also been shown to protect against mutagenesis, cell transformation, and carcinogenesis which might be termed subacute and late toxicities. The protective mechanisms are not fully elucidated but oxygen free radical scavenging certainly plays a role and effects of enzymatic DNA repair mechanisms have also been reported. In the field of reduction of toxicity from anticancer treatment modalities, the properties of CSFs and other substances have been contrasted with WR-2721 the former being stimulators of bone marrow (and the immune system) rather than true protectors. Nonetheless, they also have a clinical role and combinations of a protector and stimulator may prove useful in the future. WR-2721 offers the prospect of increasing the therapeutic index of current cancer treatment and may allow the administration of higher than currently would be considered maximal tolerated doses (MTD). This may, in turn, lead to improved efficacy and the full potential of this agent is now being explored in a variety of randomized, controlled clinical trials.
McCulloch
W
W
U.S. Bioscience, Inc., W. Conshohocken, Pennsylvania 19428.
Scheffler
B J
BJ
Schein
P S
PS
D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D001853:Bone Marrow / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D004999:Amifostine