Eur J Clin Pharmacol 1994;47(1):1-16

Institut fur Anatomie, Freie Universitat Berlin, Germany.

The earliest reports on the therapeutic use of metals or metal-containing compounds in cancer and leukemia date from the sixteenth and nineteenth centuries. They were forgotten until the 1960s, when the anti-tumour activity of the inorganic complex cis-diammine-dichloroplatinum(II) (cisplatin) was discovered. This led to the development of other types of non-organic cytostatic drugs. Cisplatin has developed into one of the most frequently used and most effective cytostatic drugs for the treatment of solid carcinomas. Numerous other metal compounds containing platinum, other platinum metals, and even non-platinum metals were then shown to be effective against tumours in man and experimental tumours in animals. These compounds comprise main-group metallic compounds of gallium, germanium, tin, and bismuth, early-transition metal complexes of titanium, vanadium, niobium, molybdenum, and rhenium, and late-transition metal complexes of ruthenium, rhodium, iridium, platinum, copper, and gold. Several platnium complexes and four non-platnium-metal antitumour agents have so far entered early clinical trials. Gallium trinitrate and spirogermanium have already passed phase II clinical studies and have shown limited cytostatic activity against certain human carcinomas and lymphomas. The two early-transition metal complexes budotitane and titanocene dichloride have just reached the end of phase I clinical trials and have been found to have an unusual pattern of organ toxicity in man. Titanocene dichloride will soon enter phase II clinical studies.

Publication Types:

• Review
• Review, academic

PMID: 7988618, UI: 95080318

J Endocrinol Invest 1991 Jun;14(6):475-80

Divisione Oncologia Medica, U.L.S.S. N. 21, Padova, Italy.

Twenty-two advanced consecutive thyroid cancer patients with varying histologies were treated with the so called BAP regime which consisted of bleomycin (B) 30 mg a day for three days, adriamycin (A) 60 mg/m2 iv in day 5, and cisplatinum (P) 60 to mg/m2 iv in day 5. Patients with progressive, symptomatic recurrent or disseminated disease unresponsive to hormonal and/or isotopic treatment were eligible. Nine patients had an objective response: two long-lasting complete and seven partial responses were observed out of 21 evaluable patients. Stable disease was observed in four additional patients. The median duration of response was 12 months (range, 6-29). The total series experienced a median survival of 11 months (range, 1 to 57), with 2 patients actually disease free. Several histologic types of thyroid carcinoma responded, but the best responses were observed in medullary and anaplastic giant-cell carcinomas. Toxicity was reversible in all but one patient. Of the patients failing on BAP chemotherapy three responded to a four drug second line combination containing vincristine, fluorouracil, BCNU and methotrexate. BAP regime can achieve reasonable palliation, and probably increases survival, in poor-prognosis thyroid cancers.

PMID: 1723086, UI: 92129805