Phase I/II study of a cisplatin-taxol-dacarbazine regimen in metastatic melanoma.
OBJECTIVE
This phase I/II study was done to evaluate the safety and efficacy of a cisplatin-paclitaxel-dacarbazine regimen in patients with metastatic melanoma.


METHODS
Chemotherapy-naive patients with surgically unresectable stage III/IV melanoma who had measurable lesions, no brain metastasis, and an Eastern Oncology Cooperative Group performance status of 0 or 1 were enrolled. Cohorts of 4 patients were treated at each dose level. The starting doses of the drugs were as follows: cisplatin 20 mg/m2 IV on days 1 to 4, paclitaxel 100 mg/m2 IV on days 1 and 8, and dacarbazine 800 mg/m2 IV on day 1 only. The doses of cisplatin and paclitaxel were escalated to the next dose level, until the maximum tolerable doses were reached. The dose level without dose-limiting grade 4 toxicity was chosen for phase II part of the study. The primary end point of the phase II study was to determine the antitumor activity in terms of response rate and survival of patients.


RESULTS
The optimum chemotherapy doses for phase II study were as follows: cisplatin 20 mg/m2 on days 1 to 4, paclitaxel 120 mg/m2 on days 1 and 8, and dacarbazine 800 mg/m2 on day 1. Overall, 46 patients were enrolled in the study. Two complete and 17 partial responses were seen for an overall response rate of 41%. The median overall survival time and time to tumor progression were 11.0 and 4.3 months, respectively. Median response duration was 6.2 months. Myelosuppression and neuropathy were the dose-limiting toxicities.


CONCLUSIONS
Cisplatin-paclitaxel-dacarbazine regimen is effective in patients with advanced melanoma.
Papadopoulos
Nicholas E
NE
Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Bedikian
Agop
A
Ring
Sigrid
S
Kim
Kevin B
KB
Hwu
Wen-Jen
WJ
Gerber
Donna L
DL
Homsi
Jade
J
Hwu
Patrick
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D012878:Skin Neoplasms / Q000473:pathology*; D016019:Survival Analysis; D016896:Treatment Outcome
D003606:Dacarbazine; D017239:Paclitaxel; D002945:Cisplatin