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.

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

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

Patients who diagnosed colorectal or appendiceal neoplasms with peritoneal metastases who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy using mitomycin-C