Experimental combination and single-agent chemotherapy in human lung-tumour xenografts

Abstract

A series of human bronchial-carcinoma xenografts (3 small-cell anaplastic, 2 large-cell anaplastic and 3 adenocarcinomas) established in immune-suppressed mice were treated with combination chemotherapy based on clinical regimes. Xenograft response was assessed by the in situ endpoint of growth delay in s.c. tumours. Dose-response relationships of 3 triple-drug combinations and their component agents were explored, allowing the relative contributions of single agents in each combination to be assessed. The results demonstrate that the effects produced in the xenografts were generally consistent with clinical experience. Procarbazine, cyclophosphamide and CCNU stood out as the most effective drugs in small cell carcinoma, but were ineffective in the other histological types. These was some evidence for individuality of therapeutic response among the grafts, supporting the case for incorporating panels of histologically similar xenografts into primary drug-screening programmes to complement existing syngeneic rodent tumour systems.