Intravesical administration of pirarubicin against superficial bladder cancer: Relationship between tumor tissue concentration and exposure time in the bladder or therapeutic effect

Arakawa, Maki; Nakamura, Kogenta; Yamada, Yoshiaki; Kato, Kimihito; Katsuda, Remi; Tobiume, Motoi; Zennami, Kenji; Watanabe, Masayuki; Kato, Yoshiharu; Nishikawa, Genya; Yoshizawa, Takahiko; Aoki, Shigeyuki; Taki, Tomohiro; Mitsui, Kenji; Honda, Nobuaki; Saito, Hiroko; Hasegawa, Takaaki

doi:10.3892/etm.2011.315

Cited by 10 publications

(7 citation statements)

References 21 publications

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“…It can significantly reduce the recurrence rate of bladder cancer after TURBT. Related research [16][17][18] reported that pirarubicin can selectively act on bladder cancer cells with fast diffusion and rapid uptake, but it is rarely absorbed by normal tissues, and the content of THP in cancer cells is significantly higher than that in normal tissues. It does not affect the healing of surgical wounds and can effectively prevent the recurrence, invasion, and metastasis of bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Bladder Intravesical Chemotherapy with Three Drugs for Preventing Non-Muscle-Invasive Bladder Cancer Recurrence

Zhang

Chen

et al. 2021

Journal of Healthcare Engineering

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Epirubicin, gemcitabine, and pirarubicin are widely used as first-line drugs for intravesical chemotherapy to prevent tumor recurrence after transurethral bladder tumor resection for non-muscle-invasive bladder cancer (NMIBC). However, which drug is better is less discussed. A total of 335 NMIBC patients administered intravesical chemotherapy underwent transurethral bladder tumor resection (TURBT) in our hospital from October 2015 to October 2019. After TURBT, all the patients received standard intravesical chemotherapy. Through clinical data collection and telephone follow-up, the tumor recurrence and adverse reactions of all patients after bladder perfusion treatment were counted. Recurrence was defined as new tumor appearance in the bladder. Of the 335 patients who underwent intravesical chemotherapy, 109 patients received epirubicin and 114 patients and 112 patients were given gemcitabine and pirarubicin, respectively. According to the general information of the patients, the patients were divided into intermediate-risk and high-risk bladder cancer and compared separately. There was no statistical difference in clinical and pathological features between different groups ( P > 0.05 ). The recurrence rate of intermediate-risk bladder cancer patients shows no difference between three groups ( P > 0.05 ). As for the high-risk bladder cancer patients, it is found that the 1-year recurrence rate between three groups was not statistically significant ( P > 0.05 ), whereas the 2-year recurrence rate of patients given gemcitabine (9.87%) was significantly lower than that of epirubicin (25.37%) and pirarubicin (24.32%), and the difference was statistically significant ( P < 0.017 , Bonferroni adjusted P value). The Kaplan–Meier survival curves showed that the recurrence-free survival rate of patients received gemcitabine was significantly higher than that of the other two groups. Comparing the incidence of adverse reactions during the infusion of the three groups of patients, the differences were not statistically significant ( P > 0.05 ). In patients with high-risk non-muscle-invasive bladder cancer, the application of gemcitabine intravesical chemotherapy is related with a relatively lower recurrence rate but similar incidence of adverse reactions.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Bladder Intravesical Chemotherapy with Three Drugs for Preventing Non-Muscle-Invasive Bladder Cancer Recurrence

Zhang

Chen

et al. 2021

Journal of Healthcare Engineering

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“…Although chemotherapy of superficial bladder cancer is efficient, the high rate of recurrence remains the most significant challenge (3,4). The present study reported TRPV1 as a novel target for the treatment bladder cancer or the sensitization of bladder cancer cells to chemotherapy.…”

Section: Discussionmentioning

confidence: 56%

“…Intravesical chemotherapy is the first-line treatment for high-risk non-muscle invasive cancer after transurethral resection of the bladder tumor (TURBT) (2). However, >50% of patients with superficial bladder cancer undergoing TURBT present with recurrence or develop muscle invasion (3,4). Pirarubicin (THP) is an anthracycline drug, which is widely used for intravesical chemotherapy to treat superficial bladder cancer (5).…”

Section: Introductionmentioning

confidence: 99%

Capsaicin enhances anti-proliferation efficacy of pirarubicin via activating TRPV1 and inhibiting PCNA nuclear translocation in 5637 cells

Zheng

Chen

et al. 2015

Molecular Medicine Reports

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The recurrence of bladder cancer after surgery with or without chemotherapy remains a major challenge in bladder cancer treatment. Previous studies have shown that transient receptor potential vanilloid 1 (TRPV1) acts as a tumor suppressor through inducing apoptosis in bladder cancer cells. However, whether activation of TRPV1 has any synergistic effects with pirarubicin (THP), one of main drugs used in urinary bladder instillation chemotherapy to improve chemotherapeutic efficacy has remained elusive. The present study verified that TRPV1 was differentially expressed in bladder cancer cell lines. Furthermore, activation of TRPV1 by capsaicin was shown to induce growth inhibition of 5637 cells in which TRPV1 was highly expressed, while the growth of T24 cells, which express TRPV1 at low levels, was not affected. In addition, the present study demonstrated that activation of TRPV1 enhanced the anti‑proliferative effects of pirarubicin using an MTT assay and cell cycle analysis. Finally, immunofluorescent microscopy revealed that activation of TRPV1 prevented the translocation of proliferating cell nuclear antigen to the nucleus. This phenomenon was reversed by pre‑treatment with capsazepine, a specific TRPV1 antagonist. In conclusion, the present study confirmed the anti‑tumor activity of TRPV1 against bladder cancer. Activation of TRPV1 may be applied as a novel strategy to treat bladder cancer or enhance the therapeutic efficacy of traditional chemotherapeutic drugs.

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“…Intravesical chemotherapeutic agents, such as mitomycin C and gemcitabine, are absorbed into the blood (Dalton et al, 1991;Campodonico et al, 2007). Meanwhile, the systemic absorption of pirarubicin is not detected in intravesical instillation after TURBT for patients with NMIBC (Arakawa et al, 2011). The rapid uptake of pirarubicin by tumor cells may contribute to the less systemic absorption (Kunimoto et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

Safety Assessment of Ultrasound-Assisted Intravesical Chemotherapy in Normal Dogs: A Pilot Study

et al. 2022

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Intravesical chemotherapy after transurethral resection is a treatment option in patients with non-muscle invasive bladder cancer. The efficacy of intravesical chemotherapy is determined by the cellular uptake of intravesical drugs. Therefore, drug delivery technologies in the urinary bladder are promising tools for enhancing the efficacy of intravesical chemotherapy. Ultrasound-triggered microbubble cavitation may enhance the permeability of the urothelium, and thus may have potential as a drug delivery technology in the urinary bladder. Meanwhile, the enhanced permeability may increase systemic absorption of intravesical drugs, which may increase the adverse effects of the drug. The aim of this preliminary safety study was to assess the systemic absorption of an intravesical drug that was delivered by ultrasound-triggered microbubble cavitation in the urinary bladder of normal dogs. Pirarubicin, a derivative of doxorubicin, and an ultrasound contrast agent (Sonazoid) microbubbles were administered in the urinary bladder. Ultrasound (transmitting frequency 5 MHz; pulse duration 0.44 μsec; pulse repetition frequency 7.7 kHz; peak negative pressure −1.2 MPa) was exposed to the bladder using a diagnostic ultrasound probe (PLT-704SBT). The combination of ultrasound and microbubbles did not increase the plasma concentration of intravesical pirarubicin. In addition, hematoxylin and eosin staining showed that the combination of ultrasound and microbubble did not cause observable damages to the urothelium. Tissue pirarubicin concentration in the sonicated region was higher than that of the non-sonicated region in two of three dogs. The results of this pilot study demonstrate the safety of the combination of intravesical pirarubicin and ultrasound-triggered microbubble cavitation, that is, ultrasound-assisted intravesical chemotherapy.

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Intravesical administration of pirarubicin against superficial bladder cancer: Relationship between tumor tissue concentration and exposure time in the bladder or therapeutic effect

Cited by 10 publications

References 21 publications

Efficacy of Bladder Intravesical Chemotherapy with Three Drugs for Preventing Non-Muscle-Invasive Bladder Cancer Recurrence

Efficacy of Bladder Intravesical Chemotherapy with Three Drugs for Preventing Non-Muscle-Invasive Bladder Cancer Recurrence

Capsaicin enhances anti-proliferation efficacy of pirarubicin via activating TRPV1 and inhibiting PCNA nuclear translocation in 5637 cells

Safety Assessment of Ultrasound-Assisted Intravesical Chemotherapy in Normal Dogs: A Pilot Study

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