Relatively speaking, not many inorganic salts have been tried as potential cancer chemotherapeutic agents. Some thirty-three metallic chlorides were evaluated both for their effect on chick embryos and on different rodent tumor systems; no unusual results were reported.

Wherever some positive results were claimed, the elements involved were usually the transition element ions. The inorganic complex (Werner's) salts of cobalt were reported as somewhat carcinolytic for Yoshida carcinoma, but the life span of these rats was not prolonged. Zinc salts have had some effect on induced tumors.

In the clinic, some decades ago, a number of metals and salts were used therapeutically. Fowler's solution, a suspension of lead arsenate in benzene, was the first remedy extensively tested. Colloidal lead or lead phosphate was also given extensive clinical trial, and 63 out of 566 patients were reported cured. Minute amounts of copper, lead, bismuth, ruthenium and selenium were also administered at various times to patients. Diets containing high potassium and low sodium salts were given to a few humans with skin tumors, and temporary remissions were reported.

More and more metal chelates are being tested for tumor inhibitory properties, and often positive effects are reported. Fair success was achieved with a zinc complex of a riboflavin-like compound. Some interesting mixed chelates have been made from anti-tumor agents. Cobalt complexes of 8-azaguanine and histidine were active against the Yoshida sarcoma, and it is postulated that the cytochrome oxidase system is affected. A cobalt-containing natural product is effective in humans, too. In about 50% of cases of neuroblastoma in children, regressions occurred if massive doses of vitamin B12 were used for treatment. Cobalt cysteine complexes with thiourea or mapharsen extended the life span of mice with Ehrlich ascites tumors.

Copper complexes of 1-hydroxyphenazine prolonged the life of leukemic mice. A series of copper oxime chelates were also found active in Sarcoma 180 and Ehrlich ascites tumor. The nickel, cobalt, zinc, iron, magnesium, manganese and mercury ions were not effective. Mercury hematoporphyrin complex, on the other hand, was effective for animal tumors and was subsequently tried in clinical cases with equivocal results. On the Ehrlich ascites tumor potassium and copper hematoporphyrin did show positive results too. The ru-beanate complexes of copper, lead and even cadmium had an anti-tumor effect on rodent tumors, whereas the rubeanic acid itself was ineffective. Another cadmium salt, cadmium ascorbate, retarded tumor growth, as did the malic salt of manganese. An interesting observation is a propos here. Only iron salts seem to be missing from the metal salts or complexes reported as inhibitors of tumor growth. On the contrary, in the few cases where reports are made of iron compounds, they seem to be carcinogenic, or stimulate growth of tumors. One should, therefore, be cautious about injecting iron salts or complexes over a long period. There are many iron preparations available for use. Iron dextran has been discussed. All others, iron salts and preparations given parenterally, should be tested as potential carcinogenic agents. Iron injected into rats implanted with adenocarcinoma BS had little effect on retarding the development of anemia associated with this cancer.

Bismuth compounds of EDTA showed significant retardation of experimental tumor growth. It would also be expected that some arsenic compounds should have anti-tumor activity, recalling Fowler's solution. Such is the case. Near maximum-tolerated doses were required, however, before tumor-inhibiting results were noted.