Radiofrequency-Induced Thermo-Chemotherapy Effect (Rite) for Non Muscle Invasive Bladder Cancer Treatment: Current Role and Perspectives

Colombo, Renzo; Valenberg, Hans van; Moschini, Marco; Witjes, J. Alfred

doi:10.5301/uro.5000197

Cited by 8 publications

(8 citation statements)

References 34 publications

(63 reference statements)

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“…To date however, the regimen of treatment, including induction and maintenance, has not reached the definition of a standard schedule. Thus, further studies are needed to achieve a more solid clinical evidence [72]. Moreover, the knowledge of pharmacodynamics after the intravesical drug administration is crucial to understand the drug diffusion through bladder tissue and improve the development of novel drug delivery technologies [73].…”

Section: Resultsmentioning

confidence: 99%

“…This was also proven clinically: RecurrenceFree Survival (RFS) was significantly improved compared to the drug alone (53% versus 15% in a 10-year follow-up on an RCT, p<0.001) as reported by Colombo et al [53]. In that clinical trial, a dedicated device was used (Synergo ® SB-TS 101, Medical Enterprises Europe B.V., The Netherlands), generating 915MHz Radiofrequency (RF) electromagnetic waves in conjunction with the instillation of a cytotoxic solution, and was described extensively previously [54,55]. It employs the RITE (Radiofrequency-Induced ThermoChemotherapeutic Effect) mode of action, combining the simultaneous tri-modality of local, non-ionizing RF radiation, a constantly cooled chemo instillation and tissue hyperthermia achieved by the RF.…”

Section: The Rite Mechanism (Radiofrequency-induced Thermochemotherapmentioning

confidence: 95%

“…This technique also minimizes the inter-patient variability and increases patients' tolerability, and has been used throughout the years with RITE [54][55][56][66][67][68][69][70][71].…”

Section: Pharmacokinetics In Rite and "Dose Splitting"mentioning

confidence: 99%

See 2 more Smart Citations

Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics

Campodonico

Stasi

Lev³

et al. 2017

CDM

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Background: Tumor recurrence is the most expected clinical event after the resection of non-muscle invasive bladder cancer, depending on histological findings of the initial lesion. In patients with low and intermediate risk of disease, the intravesical instillation of chemotherapy agents is recommended as a standard treatment to reduce recurrences. Methods:A comprehensive review covering various aspects of different treatments with intravesical drugs is presented.Results: Drugs may be instilled into the bladder starting with a single, 'early' postoperative administration or, after tumor resection with adjuvant intent or, before tumor resection under a neo-adjuvant regimen. Both latter protocols would consist of weekly treatments followed by monthly maintenance treatments. Different methods of administering drugs intravesically have been proposed to enhance the depth of drug penetration and its absorption into the bladder wall thus increasing the rate of drug-DNA reaction. These device-assisted therapies therefore have set a goal to potentiate the drug's effect and efficaciousness. The Radiofrequency-Induced Thermochemotherapeutic Effect (RITE) and the Electromotive-Drug Administration (EMDA) are the two most relevant modalities used to increase the activity of intravesical chemotherapy. Despite the widely adopted international guidelines' recommendations, and recent clinical trials of device-assisted chemotherapy instillations showing markedly enhanced recurrence-free survival compared even to the standard of care, clinicians and pharmacologists are not familiar with the in-depth physical aspects, pharmacokinetics and systemic absorption of chemotherapeutic drugs following their intravesical administration. Conclusion:Knowledge of drug diffusion mechanisms into the tissue and cellular cytoplasm following bladder instillation is a key to understand the safety profile and clinical activity of chemotherapy.

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Section: Resultsmentioning

confidence: 99%

Section: The Rite Mechanism (Radiofrequency-induced Thermochemotherapmentioning

confidence: 95%

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Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics

Campodonico

Stasi

Lev³

et al. 2017

CDM

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“…The subsequent intravesical instillation of Bacillus Calmette–Guérin (BCG) and chemotherapeutic drugs are used to prevent cancer recurrence. However, up to 50% of patients still have tumor recurrence within 5 years [ 6 , 7 ]. The reason of bladder cancer recurrence is difficult to explain, which may be related to the existence of cancer stem cells, tumor dissemination, and sporadic tumor micro foci after TURBT [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Strategies to Get Drugs across Bladder Penetrating Barriers for Improving Bladder Cancer Therapy

et al. 2021

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Bladder cancer is a significant public health concern and social burden due to its high recurrence risk. Intravesical drug instillation is the primary therapy for bladder cancer to prevent recurrence. However, the intravesical drug therapeutic effect is limited by bladder penetrating barriers. The inadequate intravesical treatment might cause the low drug concentration in lesions, resulting in a high recurrence/progression rate of bladder cancer. Many strategies to get drugs across bladder penetrating barriers have been developed to improve intravesical treatment, including physical and chemical methods. This review summarizes the classical and updated literature and presents insights into great therapeutic potential strategies to overcome bladder penetrating barriers for improving the intravesical treatment of bladder cancer.

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“…Meta-analyses of some disease sites have pointed to a therapeutic advantage of using hyperthermia . Examples of clear successes include thermoradiotherapy for locally advanced cervix and head and neck cancer and thermochemotherapy for nonmuscle invasive bladder cancer . However, more work needs to be done to prove survival advantage vs standard of care for these and other sites.…”

mentioning

confidence: 99%

Technological Advances, Biologic Rationales, and the Associated Success of Chemotherapy With Hyperthermia in Improved Outcomes in Patients With Sarcoma

Dewhirst

Kirsch

2018

JAMA Oncol

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Soft tissue sarcomas are a heterogeneous group of mesenchymal tumors that account for approximately 12 000 new cancer cases and almost 5000 deaths each year in the United States.For large (>5 cm), high-grade sarcomas of the extremity, surgical resection and radiation therapy can achieve local control in approximately 90% of patients. 1,2 However, these patients are at risk for developing metastases to the lung. Therefore, in some sarcoma centers, patients with high-risk, localized sarcoma also receive chemotherapy. Even with systemic therapy, many patients die. Therefore, the European Organization for Research and Treatment of Cancer (EORTC) initiated a multinational, multi-institutional phase 3 randomized clinical trial (EORTC 62961-ESHO 95) to evaluate whether adding regional hyperthermia to chemotherapy improves outcomes for patients with localized high-risk soft tissue sarcoma.In this issue of JAMA Oncology, Issels et al 3 report the longterm outcomes for patients enrolled on EORTC 62961-ESHO 95, which compared neoadjuvant doxorubicin, ifosfamide, and etoposide chemotherapy alone to neoadjuvant chemotherapy with regional hyperthermia. Just over half of the patients had nonextremity sarcomas, which have a higher risk for local recurrence and death as a consequence of local recurrence. In addition to hyperthermia improving local progression-free survival (hazard ratio, 0.65; 95% CI, 0.49-0.86; P = .002), with a median follow-up of 11.3 years, compared with chemotherapy alone, hyperthermia improved survival from disease or its treatment by 11.4% and 9.9% at 5 and 10 years. This trial 3 demonstrates that regional hyperthermia increases the effectiveness of neoadjuvant chemotherapy in this extremely recalcitrant tumor type.Modern interest in the use of hyperthermia as a cancer treatment emerged from a number of laboratories in the 1970s, although references to its use trace back to Hippocrates. 4 Hyperthermia interacts synergistically with radiotherapy, as well as a number of chemotherapeutic agents. Pleiotropic effects contribute to synergism, as hyperthermia enhances drug uptake by cells, inhibits the ability of cells to repair damage incurred by chemotherapy, and increases intracellular oxidative stress. Anthracyclines, ifosfamide, and etoposide were used in this trial. 3 The first 2 drugs interact synergistically with hyperthermia. 4 A further benefit of hyperthermia is that it reverses anthracycline drug resistance. At the tissue level, hyperthermia increases tumor perfusion and reduces hypoxia. The choice of using hyperthermia in a neoadjuvant setting in soft tissue sarcoma, which is hypoxic, underperfused, and relatively drug resistant, was based on this extensive biologic rationale.

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Radiofrequency-Induced Thermo-Chemotherapy Effect (Rite) for Non Muscle Invasive Bladder Cancer Treatment: Current Role and Perspectives

Cited by 8 publications

References 34 publications

Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics

Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics

Strategies to Get Drugs across Bladder Penetrating Barriers for Improving Bladder Cancer Therapy

Technological Advances, Biologic Rationales, and the Associated Success of Chemotherapy With Hyperthermia in Improved Outcomes in Patients With Sarcoma

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