Body surface area‐based vs concentration‐based perioperative intraperitoneal chemotherapy after optimal cytoreductive surgery in colorectal peritoneal surface malignancy treatment: COBOX trial

Abstract

Background and Objectives Cytoreductive surgery (CRS) and hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) are the standard of care for patients diagnosed with colorectal peritoneal surface malignancy (PSM). Despite a clearly defined standardization of CRS, a large variety of HIPEC modalities are still used in clinical practice. Methods Body surface area (BSA)‐ and concentration‐based HIPEC protocols were clinically and pharmacologically evaluated in a randomized phase III clinical pilot trial. Oxaliplatin dose was 460 mg/m 2 (BSA‐based) in 2 L/m 2 carrier solution (concentration‐based). Platinum quantification was performed using a validated inductively coupled plasma mass spectrometry method. Three‐month morbidity, mortality, and health‐related quality of life (HRQOL) were assessed. Results Thirty‐one patients were randomized to either BSA‐ or concentration‐based HIPEC. Toxicity and efficacy were higher (P < 0.001) in patients receiving concentration‐based HIPEC. There was no difference in pharmacologic advantage between the two groups. A higher drug concentration in the tumor nodule at the end of HIPEC was found in the HIPEC‐concentration group. There was no difference in major morbidity and mortality between the treatment groups. HRQOL was decreased 3 months postoperatively in the HIPEC‐concentration group. Conclusion Concentration‐based chemotherapy delivers the drug in the most standardized way to the tumor nodule, resulting in increasing drug concentrations in the tumor nodule without increasing major morbidity.

Wide variation in tissue, systemic, and drain fluid exposure after oxaliplatin-based HIPEC: results of the GUTOX study

“…Although these findings cannot be easily extrapolated to in vivo tumour nodules in patients, it provides insight in the importance of the drug concentration in peritoneal fluid. As diffusion is the most dominant mechanism to penetrate in tissue for low-molecular-weight drugs, such as cisplatin and mitomycin C, higher drug concentration in peritoneal fluid results in higher drug concentration in tumour tissue [12]. Unfortunately, the optimal tissue concentration that is required to eliminate peritoneal metastases is unknown.…”

Perioperative FOLFOX in management of peritoneal metastases of colorectal cancer. Case report of 2 patients

“…This dosimetry of intraperitoneal oxaliplatin can be contrasted to the drug administration in the PRODIGE 7 protocol. The ultra-high dose of oxaliplatin (460 mg/m 2 ) was only about one-third absorbed in the short 30-minute intraperitoneal treatment [ 20 ]. The regional dose intensity was markedly reduced as compared to the study by Stewart et al The area under the curve for these two methods for oxaliplatin administration are different.…”

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

“…Similarly, the COBOX trial showed recently that toxicity and efficacy of concentration based HIPEC protocols in patients suffering from colorectal PSM was higher. It was stated that the concentrationbased application is the most standardized way of chemotherapy delivering to the tumor tissue [16]. However, in both current dosing regimens, BSA is used as an estimate of PSA even if CRS has been performed before.…”