PHASE-I CLINICAL-TRIAL AND PHARMACOKINETICS OF 4'-CARBOXYPHTHALATO-(1,2-DIAMINOCYCLOHEXANE)PLATINUM(II)

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (11) , 4831-4835
Abstract
4''-Carboxyphthalato(1,2-diaminocyclohexane)platinum(II), [DACCP] is a new, 2nd-generation platinum analog. A phase I trial with this agent was performed in 45 patients with advanced refractory cancers. Nine dosage levels, from 40-800 mg/m2, were studied. Major toxicities seen were myelosuppression, nephrotoxicity (which was generally mild), nausea and vomiting (which was quantitatively less than that seen with cis-platin), allergic reactions and a peripheral neuropathy. The dose-limiting toxicity was thrombocytopenia. Pharmacokinetics performed at 3 dosage levels indicates that DACCP has a long t1/2 [half-life] of 20-30 h (total Pt) and is only partially excreted in the urine and that a high proportion of the drug is nonfilterable within 30-60 min of administration. Therapeutic responses were seen in nasopharyngeal carcinoma, adenocarcinoma of the cervix, and lung and gastric cancer. As a starting dose for phase II studies, 640 mg/m2 given every 3-4 wk was recommended.