Variation in Clinical Application of Hyperthermic Intraperitoneal Chemotherapy: A Review

Abstract

Peritoneal metastasis (PM) originating from gastrointestinal and gynecological malignancies are associated with a poor prognosis and rapid disease progression. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment option with curative intent. Hyperthermia enhances the cytotoxicity of chemotherapeutic drugs, thereby killing microscopic tumors and reducing the risk of tumor recurrence. Eight parameters potentially have an impact on the efficacy of HIPEC: the type of drug, drug concentrations, carrier solution, volume of the perfusate, temperature of the perfusate, duration of the treatment, the technique of delivery, and patient selection. In this review, a literature search was performed on PubMed, and a total of 564 articles were screened of which 168 articles were included. Although HIPEC is a successful treatment, there is no standardized method for delivering HIPEC: the choice of parameters is presently largely determined by institutional preferences. We discuss the current choice of the parameters and hypothesize about improvements toward uniform standardization. Quantifying the effect of each parameter separately is necessary to determine the optimal way to perform HIPEC procedures. In vivo, in vitro, in silico, and other experimental studies should shed light on the role of each of the eight parameters.

Optimal perfusion chemotherapy: A prospective comparison of mitomycin C and oxaliplatin for hyperthermic intraperitoneal chemotherapy in metastatic colon cancer

“…However, the parameters in which HIPEC is delivered is largely determined by institutional protocol with a lack of universal standardization, which limits consistency across institutions. One such parameter is the type of drug‐infused into the peritoneal cavity 14 . The mitomycin C (MMC) and oxaliplatin (Oxali) are two alkylating agents that are traditionally used for treatment of CRC with PC.…”

The PEritoneal SUrface CAlculator (PESUCA): A new tool to quantify the resected peritoneal surface area after cytoreductive surgery

“…The lack of HIPEC procedure standardization could explain contradictory study results [14]. One of the eight parameters influencing HIPEC efficacy is the exact dosing regimen of chemotherapeutic drugs [5,6]. Sugarbaker et al [15] assumed that predictions regarding chemotherapy toxicity would be less precise if drug dose and carrier solution volume are not calculated by BSA.…”

“…Despite promising results showing its efficacy in the treatment of abdominal and pelvic malignancy, there is no standardized protocol for the use of HIPEC. Eight parameters affecting HIPEC efficacy are described so far: choice of chemotherapeutic agent, carrier solution, dosing regimen, perfusate volume, temperature, procedure duration, delivery technique, and adequate patient selection [5,6]. An important controversial issue is the choice of chemotherapeutic dosing regimen.…”

Short-term oxaliplatin exposure according to established hyperthermic intraperitoneal chemotherapy (HIPEC) protocols lacks effectivenessin vitroandex vivo

“…Hyperthermic intraperitoneal chemotherapy (HIPEC) was introduced about four decades ago (1, 2) and it is meanwhile an established treatment option for peritoneal metastasis (PM), in combination with cytoreductive surgery (CRS). This approach of complete macroscopic surgical tumor removal combined with immediate intraoperative heated abdominal chemotherapy lavage was adopted worldwide and is currently most common in the treatment of PM from colorectal (CRC) and ovarian cancers (OvCa) (3). In contrast to CRS, where attempts of standardization do exist (4) and a learning curve for surgical improvement is well-established (5,6), HIPEC treatment remains very heterogeneous (3,7).…”

“…This approach of complete macroscopic surgical tumor removal combined with immediate intraoperative heated abdominal chemotherapy lavage was adopted worldwide and is currently most common in the treatment of PM from colorectal (CRC) and ovarian cancers (OvCa) (3). In contrast to CRS, where attempts of standardization do exist (4) and a learning curve for surgical improvement is well-established (5,6), HIPEC treatment remains very heterogeneous (3,7). A theoretical basis providing a rationale for adding HIPEC to CRS is the pharmacokinetic advantage of exposing malignant cells directly to high drug concentrations (8) as well as a compartmental effect called peritonealplasma barrier (9), which presumes that peritoneal malignancies are only insufficiently reached by intravenous (i.v.…”