Abstract
Human head and neck tumours were successfully transplanted in athymic nude mice. In 14 xenograft lines the effect of 1 to 3 clinically active agents could be tested. Maximum tolerated doses were given daily for 3-7 days. Growth delay was estimated in terms of the number of volume doubling times gained by the treatment. Cis-platinum and bleomycin appeared to be effective agents. In all 6 lines in which cis-platinum was examined, growth delay sometimes followed by complete regression was achieved. In 6/7 lines a response to bleomycin was observed. There was wide variation in sensitivity to cis-platinum and bleomycin among the different lines. Methotrexate, effective in 40-60% of patients with head and neck cancer, essentially showed no activity. Methotrexate produced a minimal growth delay in 1/11 lines treated. Two of the patients from whom xenografts were obtained responded to methotrexate treatment. The observed lack of activity of methotrexate against these tumour xenografts indicates that this model has limitations in the screening of new anticancer agents.
Highlights
Lactate dehydrogenase (LDH) isoenzyme analysis of the xenografts showed that >80% of the LDH in the tumour was of human origin (Pesce et al, 1977)
Three clinically active drugs were tested on 14 head and neck cancer xenograft lines, established in athymic nude mice
This study shows that, using schedules with daily injections, CDDP was an effective agent; in all 6 xenograft lines a significant growth delay was found
Summary
Female nude mice (B10.LP/Cpb, 8-10 weeks old) were obtained from the Centraal Proefdierenbedrijf TNO (Zeist, the Netherlands). Head and neck tumours from previously untreated patients were selected for implantation. Tumour material was dissected in slices measuring 3 x 3 x 1 mm and implanted s.c. in the lateral thoracic region on both sides of the animal. Tumours growing in nude mice were serially transplanted in a similar way. Tumour growth was measured biweekly using vernier calipers. Tumour volume was calculated as length x width x height x 0.5 (Looney et al, 1973). Twelve lines were established in this laboratory, of which 8 were reported recently in detail (Braakhuis et al, 1983). Two lines (HNX-J and -V) were described by Lindenberger (1981). Lactate dehydrogenase (LDH) isoenzyme analysis of the xenografts showed that >80% of the LDH in the tumour was of human origin (Pesce et al, 1977)
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