Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group.
OBJECTIVE
Temozolomide is a novel oral alkylating agent that is effective against melanoma. Moreover, temozolomide readily crosses the blood-brain barrier and may consequently be effective in patients with brain metastases. This phase II study was performed to assess the efficacy and safety of the combination regimen of temozolomide and docetaxel in patients with advanced metastatic melanoma.


METHODS
Sixty-five patients with metastatic melanoma were enrolled. Treatment consisted of intravenous docetaxel (80 mg/m(2)) on day 1 and oral temozolomide (150 mg/m(2)) on days 1 to 5, every 4 weeks, for a maximum of six cycles.


RESULTS
Sixty-two patients were eligible for the efficacy and safety analysis. Seventeen patients (27%) achieved an objective response, including five complete (8%) and 12 partial responses (19%). Median response duration was 9.5 months. Among responders, median time to progression (TTP) was 11.2 months and median overall survival (OS) was 16 months. For all treated patients, the median TTP was 4 months and median OS was 11 months. Three (38%) of eight patients who presented with brain metastases had a partial response for 5, 6, and 12 months. Of 52 patients who did not have brain involvement at presentation, only four (8%) developed brain metastases at a median follow-up of 14 months. Myelosuppression was the primary toxicity.


CONCLUSIONS
The combination of temozolomide and docetaxel was effective and well tolerated as first-line treatment for patients with advanced metastatic melanoma and demonstrated encouraging antitumor activity against brain metastases.
Bafaloukos
D
D
Metaxa's Cancer Hospital, Piraeus, Greece. hesmo@compulink.gr
Gogas
H
H
Georgoulias
V
V
Briassoulis
E
E
Fountzilas
G
G
Samantas
E
E
Kalofonos
Ch
Ch
Skarlos
D
D
Karabelis
A
A
Kosmidis
P
P
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids; D000077204:Temozolomide; D013921:Thrombocytopenia / Q000139:chemically induced
D043823:Taxoids; D000077143:Docetaxel; D003606:Dacarbazine; D017239:Paclitaxel; D000077204:Temozolomide