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

Klaver CE, Musters GD, Bemelman WA, Punt CJ, Verwaal VJ, Dijkgraaf MG, Aalbers AG, van der Bilt JD, Boerma D, Bremers AJ, Burger JW, Buskens CJ, Evers P, van Ginkel RJ, van Grevenstein WM, Hemmer PH, de Hingh IH, Lammers LA, van Leeuwen BL, Meijerink WJ, Nienhuijs SW, Pon J, Radema SA, van Ramshorst B, Snaebjornsson P, Tuynman JB, Te Velde EA, Wiezer MJ, de Wilt JH, Tanis PJ - BMC Cancer (2015)

Bottom Line: Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited.However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate.This reduction is likely to translate into a prolonged overall survival.

View Article: PubMed Central - PubMed

Affiliation: Department of surgery, Academic Medical Centre, University of Amsterdam, Post box 22660, 1105AZ, Amsterdam, The Netherlands. C.E.Klaver@amc.nl.

ABSTRACT

Background: 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.

Methods/design: 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.

Discussion: 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.

Trial registration number: NCT02231086 (Clinicaltrials.gov).

No MeSH data available.


Related in: MedlinePlus

Flow-diagram COLOPEC trial. HIPEC: hyperthermic intraperitoneal chemotherapy
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Fig1: Flow-diagram COLOPEC trial. HIPEC: hyperthermic intraperitoneal chemotherapy

Mentions: This will be a randomized controlled clinical trial of the Dutch Colorectal Cancer Group (DCCG) that will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible patients will be randomized (in a 1:1 ratio) to adjuvant HIPEC followed by standard adjuvant systemic chemotherapy in the experimental arm, or adjuvant systemic chemotherapy alone in the control arm (Fig. 1). Stratification factors will be tumour characteristic (T4 or perforation), surgical approach of the primary tumour resection (laparoscopy or open) and age (<65 years or ≥65 years).


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

Klaver CE, Musters GD, Bemelman WA, Punt CJ, Verwaal VJ, Dijkgraaf MG, Aalbers AG, van der Bilt JD, Boerma D, Bremers AJ, Burger JW, Buskens CJ, Evers P, van Ginkel RJ, van Grevenstein WM, Hemmer PH, de Hingh IH, Lammers LA, van Leeuwen BL, Meijerink WJ, Nienhuijs SW, Pon J, Radema SA, van Ramshorst B, Snaebjornsson P, Tuynman JB, Te Velde EA, Wiezer MJ, de Wilt JH, Tanis PJ - BMC Cancer (2015)

Flow-diagram COLOPEC trial. HIPEC: hyperthermic intraperitoneal chemotherapy
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4492087&req=5

Fig1: Flow-diagram COLOPEC trial. HIPEC: hyperthermic intraperitoneal chemotherapy
Mentions: This will be a randomized controlled clinical trial of the Dutch Colorectal Cancer Group (DCCG) that will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible patients will be randomized (in a 1:1 ratio) to adjuvant HIPEC followed by standard adjuvant systemic chemotherapy in the experimental arm, or adjuvant systemic chemotherapy alone in the control arm (Fig. 1). Stratification factors will be tumour characteristic (T4 or perforation), surgical approach of the primary tumour resection (laparoscopy or open) and age (<65 years or ≥65 years).

Bottom Line: Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited.However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate.This reduction is likely to translate into a prolonged overall survival.

View Article: PubMed Central - PubMed

Affiliation: Department of surgery, Academic Medical Centre, University of Amsterdam, Post box 22660, 1105AZ, Amsterdam, The Netherlands. C.E.Klaver@amc.nl.

ABSTRACT

Background: 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.

Methods/design: 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.

Discussion: 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.

Trial registration number: NCT02231086 (Clinicaltrials.gov).

No MeSH data available.


Related in: MedlinePlus