This study was undertaken to investigate the potential role of xenografts established from human
head and neck squamous cell carcinoma (
HNSCC) in the selection of new
anticancer agents for phase II clinical trials. Eight
HNSCC tumor lines were established in NMRI nude mice. The
tumor-bearing animals were then treated with drugs at the maximum tolerated dose level. Treatment with drugs known for their activity in 15%-30% of
HNSCC patients [
cisplatin (CDDP),
bleomycin (BLEO),
5-fluorouracil (5-Fu),
cyclophosphamide (CY), and
doxorubicin (DOX)] caused strong responses in up to 38% and moderate responses in 50%-67% of the
HNSCC tumor lines.
Methotrexate (MTX), known to cause remissions in about 40% of
HNSCC patients, was only minimally active in this model system. A clinically ineffective
drug,
amsacrine (
m-AMSA), was included as a negative control and showed no or minimal activity in all four
HNSCC lines tested. A number of experimental drugs that have promising preclinical activity were also tested.
Brequinar sodium (
Dup 785) and 10-ethyl,
10-deaza-aminopterin (10-EdAM) showed activity in three of five, and two of the four tested
tumor lines respectively.
N,N-dimethylformamide (DMF) and
5-aza-2'-deoxycytidine (5-aza-dCyd), agents with the capacity to induce differentiation in in vitro systems, showed moderate activity in 43% and 40%, and strong activity in 14% and 40% of the lines, respectively. Our results indicate that the nude mouse xenograft model may play a role in the screening of new drugs, and in particular, it could be of help in the selection of drugs to be tested in phase II
HNSCC clinical trials.