Weekly paclitaxel and high-dose 5-fluorouracil plus leucovorin in hormone-refractory prostate cancer: In vitro combined effects and a Phase II trial

Lin, Chia-Chi; Hsu, Chih-Hung; Hour, Tzyh-Chyuan; Cheng, Ann-Lii; Huang, Chao-Yuan; Huang, Kuo-How; Chen, Jun; Pu, Yeong-Shiau

doi:10.1016/j.urolonc.2006.06.002

« Previous Next »Urologic Oncology: Seminars and Original Investigations
Volume 25, Issue 3 , Pages 207-213, May 2007

Weekly paclitaxel and high-dose 5-fluorouracil plus leucovorin in hormone-refractory prostate cancer: In vitro combined effects and a Phase II trial

Chia-Chi Lin, M.D., Ph.D.
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
Chih-Hung Hsu, M.D., Ph.D.
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
Tzyh-Chyuan Hour, Ph.D.
- Institute of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan
Ann-Lii Cheng, M.D., Ph.D.
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Chao-Yuan Huang, M.D.
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
Kuo-How Huang, M.D.
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
Jun Chen, M.D.
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
Yeong-Shiau Pu, M.D., Ph.D.
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
- Corresponding author. Tel.:+1-886-2-23123456 ext 5249; fax: +1-886-2-23219145.

Received 13 February 2006; received in revised form 31 May 2006; accepted 1 June 2006.

Abstract

Purpose

Paclitaxel and 5-fluorouracil have been used to treat hormone-refractory prostate cancer with some success. In vitro data suggest that the combined cytotoxicity may be sequence dependent. Thus, we explored the combined effects of the 2 agents, both in vitro and in vivo.

Patients and Methods

The combined cytotoxicity of paclitaxel and 5-fluorouracil, and the possible schedule dependence were studied in vitro using PC-3 and DU145 cells and the microculture tetrazolium assay. There were 23 patients with hormone-refractory prostate cancer treated with the regimen T-HDFL: paclitaxel 90 mg/m² intravenously 1 hour on days 1 and 8; 5-fluorouracil 2000 mg/m²; and leucovorin 300 mg/m² intravenous 24-hour infusion on days 2 and 9, which repeated every 21 days. The allowed percentage of bone marrow irradiation was 50%.

Results

Significant synergistic cytotoxicity was seen only when paclitaxel was given 24 hours before 5-fluorouracil. With the T-HDFL regimen, 11 (52%) of the 21 evaluable patients had ≥50% reduction of prostate-specific antigen, lasting for 6 weeks. Of the 7 patients with measurable disease, 2 had a partial response. Median overall survival was 14.1 months. Grade III/IV leukopenia occurred in 2 patients. There was no treatment-related death. Toxicities were well tolerated.

Conclusions

The combined cytotoxicity of paclitaxel and 5-fluorouracil is schedule dependent. It is feasible to administer weekly paclitaxel and high-dose 5-fluorouracil infusions in patients with hormone-refractory prostate cancer. Our findings may serve as an important rationale for future trial design.

Keywords: Prostatic neoplasms, Chemotherapy, Toxicity, Myelosuppression, Taxanes