Phase II Marker Lesion Study With Intravesical Instillation of Apaziquone for Superficial Bladder Cancer: Toxicity and Marker Response

Heijden, Antoine G. van der; Moonen, Paula M.J.; Cornel, Erik B.; Vergunst, H.; Reijke, Theo M. de; Boven, E.; Barten, Evert J.; Puri, Rajiv; Kalken, C.K. van; Witjes, J. Alfred

doi:10.1016/j.juro.2006.06.007

Cited by 62 publications

(24 citation statements)

References 18 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Van der Heijden et al [25 ] conducted a marker lesion study in patients with low-risk to intermediate-risk NMIBC, administering six intravesical instillations of 4 mg/40 ml apaziquone. The side effects of apaziquone were comparable to those of other chemotherapeutic agents used to treat NMIBC, and a histologically proven complete response rate of 67% (30/45 patients) was achieved 2-4 weeks after the last instillation.…”

Section: Apaziquonementioning

confidence: 99%

Current strategies for first and second line intravesical therapy for nonmuscle invasive bladder cancer

Hendricksen

Witjes

2007

Current Opinion in Urology

View full text Add to dashboard Cite

Primary problems in nonmuscle invasive bladder cancer are its tendency to recur and its elusiveness (especially high-risk nonmuscle invasive bladder cancer) of progression to muscle invasive disease. First-line adjuvant therapies are well established but suboptimal. Some second-line therapies are promising but should be used cautiously, because in some patients the best option is not always the conservative one.

show abstract

Section: Apaziquonementioning

confidence: 99%

Current strategies for first and second line intravesical therapy for nonmuscle invasive bladder cancer

Hendricksen

Witjes

2007

Current Opinion in Urology

View full text Add to dashboard Cite

show abstract

“…Grade 2 and 3 dysuria and hematuria were observed at doses above 8 mg/40 ml, but 4 mg/40 ml was well tolerated [61]. Apaziquone was also well tolerated in phase II studies when administered either as 6 weekly infusions at 4 mg/40 ml [62] and as a single dose administered within 6 h of TURBT [60]. In phase III studies (single dose of 4 mg/40 ml administered within 6 h of TURBT), apaziquone was well tolerated with a safety profile that was indistinguishable from placebo, with a similar incidence of adverse events (80.0% vs. 78.5%, respectively) with dysuria as the most common treatment-related adverse event in both the apaziquone and placebo group 4.6 versus 4.1%, respectively) [68].…”

Section: Clinical Efficacymentioning

confidence: 96%

“…Using an identical marker lesion study design, 31 out of a total of 46 patients with multiple pTa or pT1 tumors achieved a complete response in phase II trials at a dose of 4 mg/40 ml [62]. Marker lesion studies have been conducted for many other cytotoxic and immune response modifiers, but the complete response rate achieved by apaziquone (67%) was the highest reported complete response rate [63].…”

Section: Clinical Efficacymentioning

confidence: 99%

Efficacy, pharmacokinetic and pharmacodynamic evaluation of apaziquone in the treatment of non-muscle invasive bladder cancer

Phillips

Hendriks²,

Sweeney

et al. 2017

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

Introduction: Apaziquone (also known as EO9 and Qapzola TM ) is a prodrug that is activated to DNA damaging species by oxidoreductases (particularly NQO1) and has the ability to kill aerobic and/or hypoxic cancer cells. Areas covered: Whilst its poor pharmacokinetic properties contributed to its failure in phase II clinical trials when administered intravenously, these properties were ideal for loco-regional therapies. Apaziquone demonstrated good anti-cancer activity against non-muscle invasive bladder cancer (NMIBC) when administered intravesically to marker lesions and was well tolerated with no systemic side effects. However, phase III clinical trials did not reach statistical significance for the primary endpoint of 2-year recurrence in apaziquone over placebo although improvements were observed. Post-hoc analysis of the combined study data did indicate a significant benefit for patients treated with apaziquone, especially when the instillation of apaziquone was given 30 min or more after surgery. A further phase III study is ongoing to test the hypotheses generated in the unsuccessful phase III studies conducted to date. Expert opinion: Because of its specific pharmacological properties, Apaziquone is excellently suited for local therapy such as NMIBC. Future studies should include proper biomarkers. ARTICLE HISTORY

show abstract

“…6 Two-thirds of subjects demonstrated a complete histologic response rate at 2-4 weeks, with local side effects comparable with those of other chemotherapy instillations. 9,113 With longer follow-up, of the 31 patients who achieved a complete response, observed recurrence-free rates at one and two years were 56.5% and 49.5%, respectively. 114 These initial data support apaziquone's promise as an intravesical agent, and Phase III trials investigating its use during immediate postoperative instillation and post-TUR induction therapy are underway.…”

Section: Apaziquonementioning

confidence: 99%

Emerging intravesical therapies for management of nonmuscle invasive bladder cancer

Smaldone¹,

Tomaszewski²

2010

OAJU

View full text Add to dashboard Cite

Transitional cell carcinoma (TCC) is the second most common urologic malignancy, and 70% of patients present with superficial or nonmuscle invasive bladder cancer (NMIBC). Intravesical bacillus Calmette-Guerin (BCG) is the most effective agent for preventing disease recurrence, and the only therapy able to inhibit disease progression. However, recurrence rates as high as 30% and significant local and systemic toxicity have led to increased interest in alternative intravesical therapies. In patients refractory or intolerant to BCG, BCG-interferon α2b, gemcitabine, and anthracyclines (doxorubicin, epirubicin, valrubicin) have demonstrated durable clinical responses. Phase I trials investigating alternative cytotoxic agents, such as apaziquone, taxanes (docetaxel, paclitaxel), and suramin are reporting promising data. Novel immunomodulating agents have demonstrated promise as efficacious alternatives in patients refractory to BCG. Optimization of existing chemotherapeutic regimens using hyperthermia, photodynamic therapy, magnetically-targeted carriers, and liposomes remains an area of active investigation. Despite enthusiasm for new intravesical agents, radical cystectomy remains the treatment of choice for patients with NMIBC who have failed intravesical therapy and selected patients with naïve T1 tumors and aggressive features. This report provides a comprehensive review of contemporary intravesical therapy for NMIBC and refractory NMIBC, with an emphasis on emerging agents and novel treatment modalities.

show abstract

Phase II Marker Lesion Study With Intravesical Instillation of Apaziquone for Superficial Bladder Cancer: Toxicity and Marker Response

Abstract: The histological complete response rate after 6 consecutive instillations of apaziquone in patients with superficial bladder cancer was 67% (95% CI 51 to 80). Local side effects were comparable to side effects due to other chemotherapy instillations.

Cited by 62 publications

References 18 publications

Current strategies for first and second line intravesical therapy for nonmuscle invasive bladder cancer

Current strategies for first and second line intravesical therapy for nonmuscle invasive bladder cancer

Efficacy, pharmacokinetic and pharmacodynamic evaluation of apaziquone in the treatment of non-muscle invasive bladder cancer

Emerging intravesical therapies for management of nonmuscle invasive bladder cancer

Contact Info

Product

Resources

About