Chemosensitivity testing of human malignant melanoma. A retrospective analysis of clinical response and in vitro drug sensitivity.
BACKGROUND
Clinical response rates in the treatment of patients with disseminated malignant melanoma are low and unpredictable. Several reports have documented that clonogenic assay systems for in vitro drug testing are capable of predicting resistance to therapy in vivo and might provide guidelines to improve clinical response rates.


METHODS
Specimens from metastatic lesions of patients with malignant melanoma, predominantly 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 colonies compared with an untreated control after 7-14 days. A retrospective comparison between the in vitro drug testing result and clinical response was possible in 19 cases.


RESULTS
An average of 7.3 drugs per specimen were tested. A high degree of resistance was observed against all 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 analysis showed no clinical response in 11 cases and one mixed response in which patients received drugs that had been shown to be "resistant" in vitro.


CONCLUSIONS
These results support the concept that in vitro drug testing promises to help avoid treatment with ineffective drugs and their associated toxic side effects. Furthermore, it may increase the likelihood of obtaining a clinical response in the treatment of disseminated malignant melanoma. The major limitation in the treatment of malignant melanoma is the lack of availability of effective agents for treatment.
Schadendorf
D
D
University Hospital Rudolf Virchow, Department of Dermatology, Free University, Berlin, Germany.
Worm
M
M
Algermissen
B
B
Kohlmus
C M
CM
Czarnetzki
B M
BM
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002330:Carmustine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003606:Dacarbazine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005544:Forecasting; D006801:Humans; D066298:In Vitro Techniques; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010865:Pilot Projects; D012074:Remission Induction; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D014407:Tumor Cells, Cultured; D014751:Vindesine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D001761:Bleomycin; D003606:Dacarbazine; D004317:Doxorubicin; D016190:Carboplatin; C054368:fotemustine; D002945:Cisplatin; D014751:Vindesine; D005472:Fluorouracil; D002330:Carmustine; D008727:Methotrexate