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Peritoneal carcinomatosis is a severe disease progression in patients with intra-abdominal cancer, and it remains one of the most common causes of incurability in these cases. An aggressive strategy with cytoreductive surgery (CCR) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a therapeutic schedule focused on the local handling of this progression, with many studies showing a significant increase in the median overall survival compared to the systemic chemotherapy treatment. Examples of drugs used in this type of administration are oxaliplatin, carboplatin, cisplatin, mitomycin C, irinotecan, paclitaxel, docetaxel, doxorubicin and melphalan.
Given that this protocol is a local treatment, with no systemic effect intention, and based on the premise that the same concentration produces a similar effect and toxicity, doses should be considered in terms of concentration instead of being defined by the body surface area (BSA). It should be kept in mind that, in HIPEC, the drug does not need to be distributed in order to reach the biophase (peritoneal cavity) and, therefore, homogenous concentrations should be achieved in the instillation solution.
However, in the reviewed literature, the doses in HIPEC were defined by the BSA. In some of the studies, the method for calculating the volume of instillation was not specified. Therefore, the volume may vary depending on the capacity of the abdominal cavity to hold liquid or may be fixed for all patients [1]. Consequently, the initial drug concentration is no longer constant, and it depends on the volume of the instilled solution.
Other authors calculate both volume and dose from each patient’s BSA [2, 3]. In these cases, the initial concentration was constant for all of them. Even though BSA may be helpful to calculate the volume of instillation needed to maintain a desired flow rate in the closed-technique HIPEC, in some cases this volume may be inappropriate. For instance, the abdominal capacity can be altered by individual pathophysiological characteristics or by the relatively frequent complications in these patients (as ascites). As a result, volumes based on the anthropometric characteristics could present a poor relationship with the abdominal cavity [4]. Thus, patients with small BSA and large abdominal cavities may have an insufficient volume to cover the entire peritoneum, and subsequent increases in volume to resolve it would change the concentration at baseline. This procedure takes us away from the initial homogenous drug concentration desired, increasing the variability in the systemic and tumor exposure to the drug. In fact, a previous study showed that the plasma drug concentrations were higher, the lower the volume was [5].
In conclusion, considering the HIPEC as a local administration, with no systemic intention, we recommend using fixed concentrations instead of dosing by BSA. Although many authors actually use homogeneous concentrations when normalizing both dose and volume by BSA, it would be more practical to define a fixed concentration independent of anthropometric characteristics. Thus, the variability of the abdominal capacity would not influence the systemic and tumor exposure to the drug.
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Mas-Fuster, M.I., Ramon-Lopez, A. & Nalda-Molina, R. Importance of standardizing the dose in hyperthermic intraperitoneal chemotherapy (HIPEC): a pharmacodynamic point of view. Cancer Chemother Pharmacol 72, 273–274 (2013). https://doi.org/10.1007/s00280-013-2204-z
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DOI: https://doi.org/10.1007/s00280-013-2204-z