Combination of interferons and cytostatic drugs for treatment of advanced colorectal cancer.

Three phase I/II trials were performed in patients with metastatic colorectal cancer using immunochemotherapy--a combination of recombinant interferon beta and gamma with low doses of cytostatic drugs. The third regimen, consisting of a cytostatic component containing 5-fluorouracil plus carboplatin plus mitomycin C besides the interferons, produced a high remission rate of 47%: 14/30 patients responded. The tolerability of this protocol was good and it could be administered on an out-patient basis.

Preclinical and early clinical trial with mafosfamide as immune modulator.

Low doses of cyclophosphamide (CPA) modulate immune responses and induce complete tumor regression and cures in mice. The mechanism of action is related to the development of a T-cell-dependent immune reaction. We started a trial with mafosfamide (MAF), the active metabolite of CPA and found that the response of Ehrlich ascites-tumor (EAT) cells in vivo to this compound is biphasic.

Therapeutic effects of single-push or fractionated injections or continuous infusion of oxazaphosphorines (cyclophosphamide, ifosfamide, Asta Z 7557).

This report describes some experimental and clinical studies showing the following: (1) in animals under protection of mesna the dose of ifosfamide (Ifo) can be increased significantly; (2) fractionated administration of Ifo, cyclophosphamide (CPA), or the stabilized metabolite of cyclophosphamide (ASTA Z 7557) is less toxic than single push-injection of the same total daily dose and therapeutically more effective; and (3) in humans under the protection of mesna the continuous infusions of ifosfamide over 5 days leads to an increase of the MTD compared with single daily short-term infusion and responses in some solid tumors, e.g., soft tissue sarcomas.

Preclinical evaluation of toxicity and therapeutic efficacy of a stabilized cytostatic metabolite of cyclophosphamide (ASTA Z 7557, INN mafosfamide).

ASTA Z 7557 is a stabilized cytostatic metabolite of cyclophosphamide which forms crystals at room temperature and releases 4-OH-cyclophosphamide in aqueous solution. The LD50/30 in mice after push injection is 417 mg/kg, after fractionated administration (q 6 hours X 4) 794 mg/kg. Daily treatment times 5 gives a LD50/30 value of 200 mg/kg.