Actinomycin D (also called dactinomycin), one of a family of structurally related actino-mycins isolated from a soil fungus of the genus, Streptomyces, is the most widely used of this class of drugs. Its suggested mode of action is to inhibit the enzyme needed for synthesis of transfer-RNA, and thus to block DNA synthesis.
Dactinomycin is in standard use in the treatment of Wilms' tumor, choriocarcinoma in women, and, in combination with methotrexate and chlorambucil (an alkylating agent), testicular tumors. Its side effects involve tissues that are proliferating most rapidly, such as bone marrow and lining of the gastrointestinal tract.
Daunomycin is a new drug isolated by scientists in Italy from Streptomyces species. A drug thought to be identical to daunomycin is rubidomycin, which was isolated in France. The drug preferentially inhibits RNA synthesis both in the cell and in isolated enzyme systems in the test tube.
This drug is just coming into clinical use and extensive data on the duration of remissions are not yet available. It produces beneficial effects in patients with acute lymphocytic leukemia, acute granulocytic leukemia in adults and children, and neuroblastoma. One report commented on the high frequency of complete remissions induced by rubidomycin alone in patients with acute granulocytic leukemia. The highly unfavorable side effect of the drug is its toxicity to the heart and the possibility of cardiac failure, especially in patients receiving high total doses.
Methylglyoxal-bis-guanylhydrazone. This compound, abbreviated as methyl GAG, is of interest because of its significant activity against acute granulocytic leukemia, which has been until now consistently resistant to treatment, and its occasional effectiveness against malignant lymphoma and myeloma. Preliminary studies of solid tumors have demonstrated activity of this drug in carcinoma of the breast, lymphosarcoma, carcinoma of the lung, and carcinoma of the esophagus. The mechanism of action of the drug is unknown; several pieces of evidence suggest that it may interfere with nucleic acid and protein metabolism.
The effective dose range of methyl GAG is quite narrow; minor alterations in dose result in either greater toxicity or decreased anti-leukemia effect. Adverse effects can be severe, and include ulcerations of the lining of the mouth and other organs, gastrointestinal toxicity, bone marrow depression, and low blood sugar levels.
Methyl Hydrazine Derivative. This is one of a new class of synthetic compounds that act as general cell poisons (also called ibenzmethyzin or procarbazine). It is suggested that the agent prolongs one of the phases of cellular division and that only chromatid, no chromosome, breaks occur; the phenomenon has been explained on the basis of a very slow degradation of isolated DNA caused by the drug. Clinical studies have indicated that the agent has some activity against Hodgkin's disease and certain solid tumors, such as lung cancer. Toxicity includes adverse effects on the digestive tract and depression of white blood cells and platelets.
o,p' DDD (ortho,para prime DDD). A derivative of the insecticide, DDT, this compound has been found effective in the treatment of patients with carcinoma of the adrenal cortex.
Its use derived from an observation that administration of the insecticide, DDD, to dogs resulted in atrophy of the adrenal cortex. Although the exact mode of action of the drug is not known, it is generally believed that it directly suppresses steroid hormone production through inhibition of certain enzyme systems. The drug is of particular interest because it has an organ-specific effect. Toxicity is generally mild and consists of upsets of the digestive tract, depression of the central nervous system, and other neuromuscular disturbances.
A clinical study of 138 patients with this type of cancer showed that of 59 patients with eval-uable, measurable disease, 34 percent had objective tumor regression, with a median duration of about 7 months.