Abstract
Purpose Carcinoma in situ represents high grade anaplasia of the bladder mucosa. Intravesical immunotherapy with bacillus Calmette-Gurin is the gold standard treatment for patients with carcinoma in situ. Patients with carcinoma in situ refractory to bacillus Calmette-Gurin are candidates for major surgery such as radical cystectomy. We identified the maximum tolerated dose and the recommended dose, and evaluated the safety profile of paclitaxel-hyaluronic acid bioconjugate given by intravesical instillation to patients with carcinoma in situ refractory to bacillus Calmette-Gurin. Materials and Methods A total of 16 patients with carcinoma in situ refractory to bacillus Calmette-Gurin were enrolled in a phase I, open label, single institution study. A minimum of 3 eligible patients were included per dose level. Paclitaxel-hyaluronic acid solution (ONCOFID-P-B™) was administered for 6 consecutive weeks. The primary objective was to identify the maximum tolerated dose and the recommended dose. As secondary objectives the safety profile of ONCOFID-P-B, the pharmacokinetic profile after each instillation and the tumor response were also evaluated. Results No dose limiting toxicity occurred at any drug level evaluated. The plasma levels of the study drug were always below the lower limit of quantification at all tested doses after each instillation. A total of 11 adverse events were reported by 7 patients and 9 (60%) showed complete treatment response. Conclusions Intravesical instillation of ONCOFID-P-B for carcinoma in situ refractory to bacillus Calmette-Gurin showed minimal toxicity and no systemic absorption in the first human intravesical clinical trial to our knowledge. Finally, satisfactory response rates were observed.
Original language | English |
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Pages (from-to) | 445-449 |
Number of pages | 5 |
Journal | Journal of Urology |
Volume | 185 |
Issue number | 2 |
DOIs | |
Publication status | Published - Feb 2011 |
Keywords
- administration, intravesical
- carcinoma in situ
- Hyaluronic acid
- paclitaxel
- urinary bladder
ASJC Scopus subject areas
- Urology