Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics
2017
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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