Docetaxel-based chemotherapy as second-line treatment for paclitaxel-based chemotherapy-resistant hormone-refractory prostate cancer: a pilot study.
OBJECTIVE
To examine docetaxel (DTX)-based chemotherapy in paclitaxel (PTX)-based chemotherapy-resistant hormone-refractory prostate cancer (HRPC) to investigate the activity and degree of toxicity in a pilot study. We have previously reported on the effectiveness of combination chemotherapy with PTX, estramustine (EMP), and carboplatin against HRPC. Although many patients with HRPC initially responded to this PTX/EMP-based combination chemotherapy, most finally progressed to PTX-resistant status within a mean of less than 1 year. DTX is an inhibitor of microtubule depolymerization like PTX and has demonstrated activity against PTX-resistant metastatic tumors.


METHODS
The subjects were 15 patients with HRPC who displayed disease progression while receiving PTX/EMP/carboplatin combination chemotherapy. The patients were treated with intravenous DTX 30 mg/m2 weekly, oral EMP 10 mg/kg daily, and intravenous carboplatin (dosed to an area under the curve of 6) on day 1 of every 4-week cycle. Treatment was continued until disease progression or excessive toxicity.


RESULTS
Each patient received a median of eight consecutive cycles. The prostate-specific antigen level decreased by 50% or more in 33.3% of patients and by 90% or more in 13.3%. The median follow-up was 49.6 weeks, with median time to progression of 25.0 weeks and median overall survival of 54.0 weeks. One patient died of interstitial pneumonitis. One patient developed secondary osteomyelodysplastic syndrome. The major severe toxicities were grade 3 or 4 anemia in 66.7% of patients, leukopenia in 26.7%, and thrombocytopenia in 40.0%.


CONCLUSIONS
The results of our study have shown that DTX is comparatively active for heavily pretreated patients with PTX-resistant HRPC. However, given the significant toxicities and small subject population, well-designed Phase I-II trials of the improved regimen are warranted.
Urakami
Shinji
S
Department of Urology, Shimane University Faculty of Medicine, Izumo, Japan. shinurakami@ybb.ne.jp
Yoshino
Tateki
T
Kikuno
Nobuyuki
N
Imai
Shin
S
Honda
Satoshi
S
Yoneda
Tatuaki
T
Kishi
Hirofumi
H
Shigeno
Kazushi
K
Shiina
Hiroaki
H
Igawa
Mikio
M
D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use*; D010865:Pilot Projects; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
D000972:Antineoplastic Agents, Phytogenic; D006728:Hormones; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel