Dataset Information

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial.

ABSTRACT: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay.The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 °C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA.Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival.NCT02231086 (Clinicaltrials.gov).

SUBMITTER: Klaver CE

PROVIDER: S-EPMC4492087 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial.

Klaver Charlotte E L CE Musters Gijsbert D GD Bemelman Willem A WA Punt Cornelis J A CJ Verwaal Victor J VJ Dijkgraaf Marcel G W MG Aalbers Arend G J AG van der Bilt Jarmila D W JD Boerma Djamila D Bremers Andre J A AJ Burger Jacobus W A JW Buskens Christianne J CJ Evers Pauline P van Ginkel Robert J RJ van Grevenstein Wilhelmina M U WM Hemmer Patrick H J PH de Hingh Ignace H J T IH Lammers Laureen A LA van Leeuwen Barbara L BL Meijerink Wilhelmus J H J WJ Nienhuijs Simon W SW Pon Jolien J Radema Sandra A SA van Ramshorst Bert B Snaebjornsson Petur P Tuynman Jurriaan B JB Te Velde Elisabeth A EA Wiezer Marinus J MJ de Wilt Johannes H W JH Tanis Pieter J PJ

BMC cancer 20150524

<h4>Background</h4>The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intrap ...[more]

PMID: 26003804

Similar Datasets

Project description:BackgroundGastric cancer patients with peritoneal carcinomatosis (PC) have a poor prognosis, with a median overall survival of 10 months when treated with systemic chemotherapy only. Cohort studies showed that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) might improve the prognosis for gastric cancer patients with limited PC. Besides generating trial data on clinical effectiveness, it is crucial to timely collect information on economic aspects to guide the reimbursement decision-making process. No previous data have been published on the cost(-effectiveness) of CRS/HIPEC in this group of patients. Therefore, we performed an early model-based cost-effectiveness analysis of CRS/HIPEC for gastric cancer patients with limited PC in the Dutch setting.MethodsWe constructed a two-state (alive-dead) Markov transition model to evaluate costs and clinical outcomes from a Dutch healthcare perspective. Clinical outcomes, transition probabilities and utilities were derived from literature and verified by clinical experts in the field. Costs were measured using two available representative cohorts (2010-2017): one 'systemic chemotherapy only' cohort and one 'CRS/HIPEC' cohort (n = 10 each). Incremental cost-utility ratios (ICURs) were expressed as Euros per quality-adjusted life-year (QALY). We performed probabilistic and deterministic sensitivity, scenario, and value-of-information analyses using a willingness-to-pay (WTP) threshold of €80,000/QALY, which reflects the Dutch norm for severe diseases.ResultsIn the base-case analysis, CRS/HIPEC yielded more QALYs (increment of 0.68) and more costs (increment of €34,706) compared with systemic chemotherapy only, resulting in an ICUR of €50,990/QALY. The probability that CRS/HIPEC was cost effective compared with systemic chemotherapy alone was 64%. To reduce uncertainty, the expected value of perfect information amounted to €4,021,468. The scenario analyses did not alter the results and showed that treatment costs, lifetime health-related quality of life and overall survival had the largest influence on the model.ConclusionsThe presented early cost-effectiveness analysis suggests that adding CRS/HIPEC to systemic chemotherapy for gastric cancer patients with limited PC has a good chance of being cost-effectiveness compared with systemic chemotherapy alone when using a WTP of €80,000/QALY. However, there is substantial uncertainty in view of the current available data on effectiveness. Results from the ongoing phase III PERISCOPE II trial are therefore crucial for further decisions on treatment policy and its cost-effectiveness.

Project description:BackgroundThe peritoneal surface is the second most common site of disease recurrence, after the liver, following definitive surgery for colorectal cancer. Adjuvant intraperitoneal (IP) chemotherapy delivered at time of surgical resection has the potential to delay or prevent future spread to the peritoneal surface and improve clinical outcome. The exact role of adjuvant IP chemotherapy in colorectal cancer, including its associated morbidity and mortality, is not well defined.Study designSystematic review and pooled random effect analysis of comparative trials examining the addition of adjuvant IP chemotherapy compared to surgery alone in colorectal cancer. The primary outcome was overall survival, and the secondary outcomes were of post-operative morbidity and mortality.ResultsIn nine colorectal cancer studies identified, seven were two-arm trials comparing adjuvant IP chemotherapy to surgery alone. Of these, four trials had outcome reporting and met criteria that allowed inclusion into a random effects model. Heterogeneity was measured by Cochran's Q-test (Q = 13.9; p = 0.01) and random effect models were utilised. Pooling eligible trials together revealed a 0.55 odds ratio of death associated with the administration of IP chemotherapy compared to surgery alone (CI = 0.31, 0.98; p = 0.04). Trials selecting patients at elevated risk for the development of peritoneal carcinomatosis by clinicopathological biomarkers for administration of adjuvant IP chemotherapy reported more favourable overall outcomes. There was no increase in mortalities or IP chemotherapy-related abdominal complication rates among patients undergoing IP chemotherapy (OR = 1.4; CI = 0.52, 3.8; p = 0.5).ConclusionsThis systematic review supports the use of adjuvant IP chemotherapy in resectable colorectal cancer at risk for peritoneal spread. Future trials should seek to standardise inclusion criteria and IP chemotherapy modalities to better define the role of this treatment in patients with resectable colorectal cancer.

Dataset Information

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial.

Publications

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets