Pharmacokinetics of intraperitoneal mitomycin C

doi:10.1016/S1055-3207(03)00031-0

Surgical Oncology Clinics of North America

Volume 12, Issue 3, July 2003, Pages 771-780

https://doi.org/10.1016/S1055-3207(03)00031-0 Get rights and content

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The pharmacokinetics of MMC

We confine our review to clinical studies dealing with hyperthermic intraperitoneal perfusion with MMC (Table 1). Ten studies have been reported [11], [12], [13], [14], [15], [16], [17], [18], [19]. Our own experience with the pharmacokinetics of MMC is discussed along with this prior information.

Summary

The favorable pharmacokinetics of MMC, used during intraperitoneal chemotherapy, has been reported in several studies [11], [12], [13], [14], [15], [16], [17], [18], [19]. A major safety issue in studies using intraperitoneal chemotherapy perfusion is the resulting systemic drug exposure. The AUC_plasma is determined by the dose, the clearance, and the fraction absorbed from the peritoneal cavity. The reported mean plasma peak concentrations are about one-third of the systemic exposure following

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Cited by (68)

Molecular mechanisms regulating wound repair: Evidence for paracrine signaling from corneal epithelial cells to fibroblasts and immune cells following transient epithelial cell treatment with Mitomycin C
2023, Experimental Eye Research
In this paper, we use RNAseq to identify senescence and phagocytosis as key factors to understanding how mitomyin C (MMC) stimulates regenerative wound repair. We use conditioned media (CM) from untreated (CMC) and MMC treated (CMM) human and mouse corneal epithelial cells to show that corneal epithelial cells indirectly exposed to MMC secrete elevated levels of immunomodulatory proteins including IL-1α and TGFβ1 compared to cells exposed to CMC. These factors increase epithelial and macrophage phagocytosis and promote ECM turnover. IL-1α supplementation can increase phagocytosis in control epithelial cells and attenuate TGFβ1 induced αSMA expression by corneal fibroblasts. Yet, we show that epithelial cell CM contains factors besides IL-1α that regulate phagocytosis and αSMA expression by fibroblasts. Exposure to CMM also impacts the activation of bone marrow derived dendritic cells and their ability to present antigen. These in vitro studies show how a brief exposure to MMC induces corneal epithelial cells to release proteins and other factors that function in a paracrine way to enhance debris removal and enlist resident epithelial and immune cells as well as stromal fibroblasts to support regenerative and not fibrotic wound healing.
A guide to establishing a hyperthermic intraperitoneal chemotherapy program in gynecologic oncology
2020, Gynecologic Oncology
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) may be used to treat peritoneal based malignancies, such as epithelial ovarian cancer (EOC). Despite results of clinical trials supporting an increasing indication for HIPEC in EOC, concerns have existed regarding morbidity and challenges with initiating HIPEC at an institutional level. The objective of this review is to describe evidence-based recommendations to guide implementation of a HIPEC program, following our experience at a high-volume tertiary care center.
Establishing a HIPEC program requires building a multi-disciplinary team, including gynecologic oncologists, anesthesia, nursing, perfusionists and pharmacists. Team members require education regarding HIPEC protocols, toxic waste and spill management, and personal protective equipment (PPE). Required equipment includes chemotherapy certified PPE and a HIPEC pump which is connected to inflow and outflow catheters placed within the peritoneal cavity. During the procedure, 3–6 L of a hyperthermic perfusate, composed of a isotonic crystalloid vehicle and the chemotherapy of choice, is infused through the peritoneal cavity with goal temperature of 41–43 °C.
Prior to HIPEC infusion, surgical teams must communicate with anesthesia and pharmacy. In patients receiving HIPEC with cisplatin, furosemide and mannitol should be administered one hour prior to chemotherapy to ensure adequate diuresis. Sodium thiosulfate may also be considered for renal protection (van Driel et al., n.d. [3]). We utilize a multi-agent pre-medication protocol prior to HIPEC infusion to reduce hypersensitivity reactions, renal toxicity and post-operative nausea and vomiting. Limited data exists to support the optimal regimen for HIPEC at the time of CRS in women with EOC. From our experience, we favor use of cisplatin 100 mg/m² alone or in combination with paclitaxel 135–175 mg/m2 with 90 min of total perfusion time. Close attention to temperature and glycemic control is essential during the procedure, as electrolyte derangements including hyperglycemia, lactic acidosis and hypokalemia may occur. Continuous patient monitoring and proactive management of abnormalities that arise during HIPEC is imperative to decrease patient morbidity and mortality.
Oxaliplatin versus Mitomycin C for HIPEC in colorectal cancer peritoneal carcinomatosis
2017, European Journal of Surgical Oncology
Compare long-term outcomes in colorectal cancer (CRC) patients with peritoneal carcinomatosis (PC) treated with peritonectomy/HIPEC using oxaliplatin versus MMC.
Peritonectomy and heated intraperitoneal chemotherapy (HIPEC) greatly improves patient survival in CRC PC. This procedure is not uniform across centres and the optimal choice of HIPEC chemotherapeutic is unclear. Oxaliplatin and Mitomycin C (MMC) are the most commonly used agents and comparative studies have reported varying results.
201 patients were retrospectively selected from the St George Hospital database, all of which had undergone peritonectomy/HIPEC for CRC PC. Oxaliplatin and MMC were used in 106 and 96 patients, respectively. Each patient's baseline characteristics, operative details, choice of chemotherapeutic agent and survival were noted.
The two groups did not differ significantly at baseline. Patients receiving oxaliplatin had significantly greater unadjusted median survival compared to MMC (56.0 ± 8.1 vs. 29.0 ± 3.4 months) which translated into a hazards ratio of 0.59 (95% CI 0.37–0.91, p = 0.017). Subgroup analysis further confirmed an advantage with oxaliplatin in females, moderate-well differentiated tumours, tumours without signet ring pathology and PCI 10–15.
Our study suggests oxaliplatin offers a survival advantage over MMC when used for HIPEC in CRC PC. Further studies to understand its efficacy, complications and ideal preparation are required. A Phase III randomised control trial comparing oxaliplatin and MMC would enhance decision-making.
Progress in treatments for colorectal cancer peritoneal metastases during the years 2010-2015. A systematic review
2016, Critical Reviews in Oncology/Hematology
Citation Excerpt :
However, no technical variation has been tested in comparative trials. Several extra-corporeal circulation devices to perform HIPEC under continuous monitoring of temperature, volume, and perfusate flow rates are commercially available (Van Ruth et al., 2003). The choice of antiblastic drugs is based on their clinical efficacy and pharmacokinetics.
Peritoneal metastases (PM) from colorectal cancer (CRC) were traditionally associated with bad prognosis. Only recently, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has resulted in survival improvements. A systematic literature search between January 2010 and June 2015 was performed. Studies were selected and appraised according to predetermined criteria. Nineteen cohort studies, and thirteen comparative studies of CRS/HIPEC were included. The weighted median overall survival was 31.6 months (range 16–51). Major morbidity was 17.6–52.4% (weighted average 32.6%). Mortality was 0–8.1% (weighted average 2.9%). Additional relevant topics, such as CRC-PM prevalence, results by systemic therapies, preoperative work-up, and technical aspects were summarized through a narrative review. The recent literature suggests that CRS/HIPEC is gaining acceptance as standard of care for selected CRC-PM patients. Refinement of selection criteria, and rationalization of comprehensive systemic and local-regional management is ongoing. Prevention and early treatment of PM are new and promising options.
Multicenter dose-escalation Phase i trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for appendiceal and colorectal peritoneal metastases: Rationale and design
2022, Pleura and Peritoneum
Optimizing regional chemotherapy for epithelial ovarian cancer
2022, Journal of Obstetrics and Gynaecology Research

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Review articlePharmacokinetics of intraperitoneal mitomycin C

Section snippets

The pharmacokinetics of MMC

Summary

First page preview

Cancer Treat Rev

Eur J Cancer

Eur J Surg Oncol

Lancet

J Am Coll Surg

Proc Am Assoc Cancer Res

Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis

Semin Surg Oncol

In vitro thermochemotherapy of human colon cancer cells with cis-dichlorodiammineplatinum(II) and mitomycin C

Cancer Res

Enhancement by hyperthermia of the in vitro cytotoxicity of mitomycin C toward hypoxic tumor cells