Severe Neutropenia After HIPEC Using Mitomycin-C

Completed

• Conditions: Cancer Metastatic to the Peritoneal Cavity; Appendiceal Neoplasm; Colorectal Cancer Metastatic; Pseudomyxoma Peritonei
• Interventions: Procedure: Intraoperative blood and peritoneal fluid samplings during HIPEC

• Registration Number: NCT05513183
• Lead Sponsor: Gangnam Severance Hospital

Brief Summary

Mitomycin-C (MMC) is the most commonly used chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) to treat colorectal cancer patients with peritoneal metastases. However, MMC has a side effect of myelosuppression. Particularly, severe neutropenia after CRS with HIPEC can be a life-threatening condition. Despite the postoperative risks of this side effect, the causes and risk factors for severe neutropenia after CRS followed by HIPEC is not identified so far. Therefore, in this study, we aimed to evaluate to evaluate clinical risk factors and pharmacologic properties after CRS with HIPEC using MMC in patients with colorectal cancer or appendiceal mucinous neoplasms with peritoneal metastases.

Detailed Description

Evaluation parameters

1. Preoperative period

* Obtaining informed consent

* Assessment of baseline clinical characteristics: vital sign, BMI, BSA, ASA classification, ECOG, CBC, CEA level

* Before 1 day of surgery, assessment of QoR-40 questionnaires

2. Intra-operative period

* CRS / HIPEC

* Assessment for peritoneal cancer index, complete cytoreduction score

* HIPEC procedures: HIPEC was performed using MMC 35 mg/m2 at 41-43℃ for 90 min. Following the HIPEC triple method, MMC 35 mg/m2 was mixed with 3L of Physioneal PD-2 1.5% peritoneal dialysis solution and administered into the intraperitoneal cavity at 50% of the dose at the beginning of HIPEC, 25% of the dose at 30 min, and 25% of the dose at 60 min.

* Intraoperative samplings of blood and peritoneal fluids during HIPEC :

* Blood sampling of 5 ml at each time point (baseline, 0 (HIPEC starting point), 15, 30, 45, 60, 75, 90, 120 min)

* Peritoneal fluid sampling of 5 ml at each time point (baseline, 0 (HIPEC starting point), 15, 30, 45, 60, 75, 90 min)

3. Postoperative period : Postoperative assessment until the discharge date or postoperative 14th days.

* Daily assessment before discharge : vital sign, transfusion, neutropenia occurrence, adverse events, hematologic blood test (CBC, absolute neutrophil count (ANC), postoperative complications, use of G-CSF, ICU admission (If severe neutropenia occurs in the postoperative period, the patient assigns in arm I.)

* CEA level: postoperative 5th day

* QoR-40 questionnaires: postoperative 4th and 7th days

Study Timeline

• Study Start: 2021-05-20
• Study First Submitted: 2022-08-18
• Study First Submitted QC: 2022-08-21
• Study First Posted: 2022-08-24
• Primary Completion: 2023-03-20
• Study Completion: 2023-03-20
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-03
• Last Update Posted: 2023-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 74

Inclusion Criteria

• Joined the study voluntarily and signed informed consent form
• Patients who diagnosed colorectal cancer or appendiceal mucinous neoplasm with peritoneal metastases
• Patients who undergo CRS/HIPEC using MMC
• ECOG ≤ 1

Exclusion Criteria

• Patients who received synchronous operations for liver or lung metastatic sites during CRS/HIPEC
• Previous histories who underwent CRS/HIPEC
• Patients who received palliative 3rd line chemotherapy
• Patients who received chemotherapy within 1 year to treat other cancers
• Patients who had PCD cathethers for ascites control
• ECOG ≥2
• Infectious status
• Age<19 years old
• Pregnant or breast-feeding women or people during the birth-period who refused to take contraceptives

Drop-out criteria

• Hospital stay > 30 days

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Arm I (Severe neutropnia group),	Intraoperative blood and peritoneal fluid samplings during HIPEC	After CRS followed by HIPEC using MMC of 35mg/m2, patients who had absolute neutrophil count (ANC) \< 1000/mm3 during the postoperative period are assigned as experimental group (Arm I, severe neutropnia group).
Arm II (No severe neutropenia group)	Intraoperative blood and peritoneal fluid samplings during HIPEC	After CRS followed by HIPEC using MMC of 35mg/m2, patients who had ANC ≥ 1000/mm3 during the postoperative period are assigned as the control group (Arm II: no severe neutropenia group).

Primary Outcome Measures

Name	Time	Method
Association between the concentration of intraoperative mitomycin-C absoprtion and severe neutropenia after CRS/HIPEC	2 weeks after the discharge	Comparison of the pharmacologic association between occurrence of postoperative severe neutropenia, and blood absoprtion rates of MMC and the area-under-the curve (AUC) ratios during HIPEC

Secondary Outcome Measures

Name	Time	Method
Changes of CEA level	During 2 weeks after CRS/HIPEC	ng/mL
Incidence of severe neutropenia	During 2 weeks after CRS/HIPEC	Incidence (rates)
Postoperative complications	During 2 weeks after CRS/HIPEC	Assessment from Clavien-Dindo classification
Frequency of postoperative uses for G-CSF	During 2 weeks after CRS/HIPEC	Numbers of G-CSF uses
Patterns of perioperative changes of WBC, Hemoglobin, platelet, lymphocyte, neutrophil counts	During 2 weeks after CRS/HIPEC	Records for serologic tests
Quality of Life: QoR-40 questionnaire	During 2 weeks after CRS/HIPEC	Answer of questionnarie

Trial Locations

Locations (1)

Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; 🇰🇷 Seoul, Korea, Republic of