Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial.

Abstract

PURPOSE:

We evaluated the efficacy of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC).

PATIENTS AND METHODS:

From December 2005 to November 2008, 77 patients clinically diagnosed with UUT-UC from 11 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were preoperatively enrolled in this study. Patients were randomly assigned to receive or not receive a single instillation of THP (30 mg in 30 mL of saline) into the bladder within 48 hours after nephroureterectomy. Cystoscopy and urinary cytology were repeated every 3 months for 2 years or until the occurrence of first bladder recurrence.

RESULTS:

Seventy-two patients were evaluable for efficacy analysis, 21 of whom had a subsequent bladder recurrence. Significantly fewer patients who received THP had a recurrence compared with the control group (16.9% at 1 year and 16.9% at 2 years in the THP group v 31.8% at 1 year and 42.2% at 2 years in the control group; log-rank P = .025). No remarkable adverse events were observed in the THP-treated group. Based on multivariate analysis, THP instillation (hazard rate [HR], 0.26; 95% CI, 0.07 to 0.91; P = .035) and open surgery (HR, 0.28; 95% CI, 0.09 to 0.84; P = .024) were independently predictive of a reduced incidence of bladder recurrence.

CONCLUSION:

In this prospective randomized phase II study, a single intravesical instillation of THP seemed to reduce bladder recurrence after nephroureterectomy. A phase III, large-scale, multicenter study is needed to confirm these observations.

• Authors: Akihiro Ito, Ichiro Shintaku, Makoto Satoh, Naomasa Ioritani, Masataka Aizawa, Tatsuo Tochigi, Sadafumi Kawamura, Hiroshi Aoki, Isao Numata, Atsushi Takeda, Shunichi Namiki, Takashige Namima, Yoshihiro Ikeda, Koichi Kambe, Atsushi Kyan, Seiji Ueno, Kazuhiko Orikasa, Shinnosuke Katoh, Hisanobu Adachi, Satoru Tokuyama, Shigeto Ishidoya, Takuhiro Yamaguchi, Yoichi Arai
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 31 Issue 11 Pg. 1422-7 (Apr 10 2013) ISSN: 1527-7755 [Electronic] United States
• PMID: 23460707 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Doxorubicin
• pirarubicin

Topics

• Administration, Intravesical
• Aged
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Carcinoma, Transitional Cell (drug therapy, pathology, surgery)
• Cystoscopy
• Doxorubicin (administration & dosage, analogs & derivatives, therapeutic use)
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Multivariate Analysis
• Neoplasm Recurrence, Local (prevention & control)
• Prospective Studies
• Treatment Outcome
• Ureter (pathology, surgery)
• Urinary Bladder Neoplasms (drug therapy, pathology, surgery)
• Urinary Tract (pathology, surgery)
• Urologic Surgical Procedures (methods)