High-dose cisplatin with dacarbazine and tamoxifen in the treatment of metastatic melanoma.
In an attempt to increase the antitumor effect of cisplatin (50 mg/m2) and dacarbazine (350 mg/m2), each repeated on days 1 to 3 every 4 weeks in patients with metastatic melanoma, tamoxifen was added to the regimen. Before the first course of chemotherapy, the patients received a loading dose of tamoxifen (100 mg orally twice a day for 7 days), followed by a maintenance dose of 10 mg orally twice a day and continued throughout the treatment. Aspirin (325 mg orally every other day) was administered at the same time as the tamoxifen in an attempt to reduce the risk of thromboembolic events. The activity of high-dose cisplatin with dacarbazine and tamoxifen was disappointing. Of 23 evaluable patients, only three responded--an overall response rate of 13% (95% confidence limits, 0% to 27%). These responses consisted of one pathologic complete remission in a patient with nodal metastases, one clinical complete remission in a patient with a very large pelvic mass, and one partial response in another patient with nodal metastases. The duration of responses was 12+, 4, and 4 months, respectively. These data do not support a significant interaction between tamoxifen and cisplatin or dacarbazine. Assuming that tamoxifen is important in the cisplatin, dacarbazine, and carmustine combination, as suggested by others, the most relevant interaction may be between tamoxifen and carmustine.
Buzaid
A C
AC
Department of Medicine, Yale New Haven Hospital, Yale University School of Medicine, Connecticut 06510.
Murren
J R
JR
Durivage
H J
HJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D004341:Drug Evaluation; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D012074:Remission Induction; D012878:Skin Neoplasms / Q000188:drug therapy*; D013629:Tamoxifen / Q000008:administration & dosage
D013629:Tamoxifen; D003606:Dacarbazine; D002945:Cisplatin; D001241:Aspirin