BLESS Trial Protocol: Reduced-dose Bleomycin Electrochemotherapy for Cutaneous Metastases Aims for Non-inferior Tumor Control

Patients with incurable cancer frequently suffer from cutaneous metastases, which cause significant pain, discomfort, and emotional distress, severely impacting their quality of life. Current treatment options often fall short in balancing efficacy with gentleness. Electrochemotherapy (ECT) offers a promising alternative by using short, high-voltage electrical pulses to transiently permeabilize tumor cells, enhancing the intracellular uptake and cytotoxic effect of chemotherapy agents like bleomycin. Traditionally, a high dose of 15,000 IU/m2 bleomycin is administered, but emerging evidence suggests that a lower dose might achieve comparable tumor control with fewer side effects, addressing a critical gap in patient care.

This article describes the protocol for the ongoing BLESS trial, a double-blinded, randomized clinical trial designed to assess the non-inferiority of ECT with a reduced bleomycin dose. Patients with cutaneous metastases are randomized to receive either half the standard bleomycin dose or the conventional 15,000 IU/m2 intravenously. The protocol meticulously details randomization and blinding procedures, comprehensive pretreatment evaluation, precise bleomycin preparation and administration, standardized electrode placement, and controlled pulse delivery. Primary endpoint is tumor control at three months, evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. The study also includes pharmacokinetic blood sampling and qualitative patient interviews for a holistic treatment impact assessment.

The BLESS trial protocol outlines a rigorous framework for evaluating dose optimization in electrochemotherapy. It details the comprehensive assessment plan, including clinical response at three months, pharmacokinetic blood sampling to understand drug exposure, and qualitative interviews to capture patient experiences. > The core objective is to determine if half the standard bleomycin dose is non-inferior to the conventional 15,000 IU/m2 regimen for achieving tumor control in patients with cutaneous metastases. The article presents baseline tumor characteristics from the first 15 enrolled patients, providing initial insights into the study population. An example of how mRECIST criteria are applied for response evaluation is also included, demonstrating the standardized approach to measuring treatment efficacy. Critical methodological steps, such as consistent electrode positioning and predefined management of confluent tumors, are discussed to ensure reproducibility and rigor.