General Information

Valstar (valrubicin) is an anthracycline topoisomerase inhibitor.

Valstar is indicated for intravesical therapy of BCG-refractory carcinoma in situ (CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality.

Valstar is for intravesical use only. Valstar is recommended at a dose of  800 mg administered intravesically once a week for six weeks. Delay administration at least two weeks after transurethral resection and/or fulguration.

Mechanism of Action

Valrubicin is an anthracycline that affects a variety of interrelated biological functions, most of which involve nucleic acid metabolism. In cells, it inhibits the incorporation of nucleosides into nucleic acids, causes chromosomal damage, and arrests the cell cycle in G2. Although valrubicin does not bind strongly to DNA, valrubicin metabolites interfere with the normal DNA breaking-resealing action of DNA topoisomerase II.

Side Effects

Adverse effects associated with the use of Valstar may include, but are not limited to, the following:

• urinary frequency
• dysuria
• urinary urgency
• bladder spasm
• hematuria
• bladder pain
• urinary incontinence
• cystitis
• urinary tract infection
• nocturia
• local burning symptoms
• abdominal pain
• nausea

Clinical Trial Results

Valstar was administered intravesically to a total of 230 patients with transitional cell carcinoma of the bladder, including 205 patients who received multiple weekly doses ranging from 200 to 900 mg. One hundred seventy-nine of the 205 patients received the approved dose and schedule of 800 mg weekly for multiple weeks. Patients receiving Valstar for refractory carcinoma in situ were monitored for disease recurrence or progression with cystoscopy, biopsy, and urine cytology every 3 months.

In the 90 study patients with BCG-refractory carcinoma in situ (CIS), 70% had received at least 2 courses of BCG and 30% had received one course of BCG and at least one additional course of treatment with another agent(s) - e.g., mitomycin, thiotepa, or interferon. Valstar  was administered beginning at least two weeks after transurethral resection and/or fulguration.

After intravesical administration of Valstar , 16 patients (18%) had a complete response documented by bladder biopsies and cytology at 6 months following initiation of therapy. Median duration of response from start of treatment varied according to the method of analysis (13.5 months if measured to last bladder biopsy without tumor and 21 months if measured until time of documented recurrence). A retrospective analysis in the 16 patients with complete response to Valstar  demonstrated that time to recurrence of their disease after treatment with Valstar  was longer than time to recurrence after previous courses of intravesical therapy.

Of the 90 patients with BCG-refractory CIS, 11% (10 patients) developed metastatic or deeply-invasive bladder cancer during follow-up; four of these patients, none who underwent cystectomy, died with metastatic bladder cancer and six were found to have developed stage progression to deeply-invasive disease (T3), with lymph node involvement in one patient, at the time of cystectomy. It is uncertain to what extent the development of advanced bladder cancer in these patients was due to the delay in cystectomy required to receive treatment with Valstar (3 months was the time of follow-up to determine response), as cystectomy was often delayed or was never performed despite failure of treatment with Valstar. In the 10 patients documented to have invasive bladder cancer or metastatic disease, the delay between the time of treatment failure (when cystectomy should have been performed) and cystectomy or documentation of advanced bladder cancer was a median of 17.5 months.