Pediatric osteosarcoma: Treatment of the primary tumor with intra-arterial cis-diamminedichloroplatinum-II. Factors demonstrating that a systemic therapeutic effect is also attained

Intra-arterial cis-diamminedichloroplatinum-II (CDP) is effective in treating the primary tumor in osteosarcoma. The strategy may be criticized on the grounds that it does not provide therapy for concurrent metastatic disease. We reviewed our experience with the use of intra-arterial CDP. This permitted an opportunity to adduce evidence that a systemic effect to treat established and micrometastases was attained. This may be summarized as follows: 1) Nausea and vomiting occurred during the infusion in almost all patients. 2) Many patients complained of a transient metallic taste and expectorated during and after treatment. 3) Approximately 20% of patients experienced transient hypertension after the second or third course. 4) A reduction in creatinine clearance occurred in practically all patients. 5) Pharmacokinetic studies revealed that with 150 mg/m² administered intra- arterially over two hours, a steady state was approached in the systemic circulation in two to three hours, attaining a serum CDP level of 3.9 microgram/ml at 120 minutes in the peripheral vein. 6) Auditory deficits developed in the majority of the patients. 7) Hyper-pigmentation developed at sites remote from the primary tumor: Particularly affected were the knuckles of the feet and hands, elbows and knees and areas around the base of the neck. Growth arrest lines in the nail beds of the fingers and toes were also encountered. 8) Finally, responses were noted in seven of eleven patients with established pulmonary metastases. These data are consonant with the premise that intra-arterial CDP, while providing an attack on the primary tumor, achieves systemic tumoricidal drug concentrations. These concentrations cause a variety of side effects and are capable of destroying metastatic disease.