A phase II trial of docetaxel (Taxotere) in hormone-refractory prostate cancer: correlation of antitumor effect to phosphorylation of Bcl-2.
Twenty-one patients with hormone refractory prostate cancer were enrolled to receive single-agent docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) 75 mg/m2 intravenously every 21 days. Six patients consented to biopsies of the prostate tumor before and following the first cycle of chemotherapy and 11 patients underwent periodic blood collection for isolation of the mononuclear cell fraction. The toxicities of treatment were moderate but included eight episodes of grade III and two episodes of grade IV nonhematologic toxicity as well as seven episodes of grade III and 11 episodes of grade IV hematologic toxicity (primarily neutropenia, including four episodes of febrile neutropenia). An objective response of more than 50% reduction in prostate-specific antigen was observed in seven patients (38%) and more than half of the patients with symptomatic disease at the initiation of therapy had improvements on treatment. Radiographic or scintigraphic evidence of tumor regression was observed in six patients. Nine patients experienced a prolonged period of stable disease on treatment (median, six cycles). Tumor specimens are currently being analyzed for bcl-2 expression and phosphorylation. The current series confirms the substantial single-agent activity of docetaxel in hormone refractory prostate cancer and may help to further elucidate its mechanism of action at the molecular level.
Friedland
D
D
Oncology-Hematology Association, Allegheny Cancer Center, and the Triangle Urological Group, Pittsburgh, PA 15212, USA.
Cohen
J
J
Miller
R
R
Voloshin
M
M
Gluckman
R
R
Lembersky
B
B
Zidar
B
B
Keating
M
M
Reilly
N
N
Dimitt
B
B
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D000077143:Docetaxel; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects*; D043823:Taxoids
D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel