Evaluation of a cooperative clinical study of the cytostatic agent ifosfamide

Abstract

In cooperative studies performed in 21 German clinics, the new cytostatic agent 3-(2-chloroethyl)-2-[(2-chloroethyl)-amino]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide (ifosfamide; trade name: Holoxan) was administered as massive-dose treatment. The studies aimed at confirming the results obtained in pharmacological and Phase I clinical trials with a fractionated administration of ifosfamide on a large scale. The study was carried out in 390 patients suffering from various malignant conditions. The majority of patients had had pretreatment without response or were admitted at an advanced stage of disease. Despite this negative selection, 25.5% of the patients showed an initial full remission and 42.3% partial remission; in 32.2% of the patients, reduction of the tumour signs by at least 50% was not attained. After an average observation period of 6 1/2 months, 53.8% of the patients were still alive. The study clearly shows the superiority of fractionated administration of ifosfamide when compared to its use as a single administration. In addition, the rates of remission and survival, and of survival times, were clearly dependent on dosage, independent of the tumour type. A daily dosage of 50 to 60 mg/kg ifosfamide on 5 consecutive days produced the best results. In spite of the fact that ifosfamide was not always given at optimum dosage, it proved to be definitely superior to conventional chemotherapy in testicular tumours, particularly teratomas and also in hypernephromas. Retrospective comparison with results of conventional chemotherapy for ovarian, bronchial and mammary cancer has shown ifosfamide to produce the same therapeutic effect in these tumour types. In this study group, leukopenia was not regarded as a limiting factor to the administration of ifosfamide. Side effects in the efferent urinary tract, particularly cystitis, were controlled with adequate preventive measures.