D. Schadendorf et al., CHEMOSENSITIVITY TESTING OF HUMAN-MALIGNANT MELANOMA - A RETROSPECTIVE ANALYSIS OF CLINICAL-RESPONSE AND IN-VITRO DRUG-SENSITIVITY, Cancer, 73(1), 1994, pp. 103-108
Background. Clinical response rates in the treatment of patients with
disseminated malignant melanoma are low and unpredictable. Several rep
orts have documented that clonogenic assay systems for in vitro drug t
esting are capable of predicting resistance to therapy in vivo and mig
ht provide guidelines to improve clinical response rates. Methods. Spe
cimens from metastatic lesions of patients with malignant melanoma, pr
edominantly from lymph nodes and skin, were disaggregated, exposed to
a panel of 10 cytotoxic drugs for 1 hour, and subsequently cultured in
agarose. Effects were calculated by the ability to form tumor colonie
s compared with an untreated control after 7-14 days. A retrospective
comparison between the in vitro drug testing result and clinical respo
nse was possible in 19 cases. Results. An average of 7.3 drugs per spe
cimen were tested. A high degree of resistance was observed against al
l cytostatic agents studied independently of the tumor site. In 47 of
181 in vitro drug tests, tumor colony formation was reduced by 30-50%;
in 17 of 181, the reduction was more than 50%. A retrospective analys
is showed no clinical response in 11 cases and one mixed response in w
hich patients received drugs that had been shown to be ''resistant'' i
n vitro. Conclusions. These results support the concept that in vitro
drug testing promises to help avoid treatment with ineffective drugs a
nd their associated toxic side effects. Furthermore, it may increase t
he likelihood of obtaining a clinical response in the treatment of dis
seminated malignant melanoma. The major limitation in the treatment of
malignant melanoma is the lack of availability of effective agents fo
r treatment.