Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2014

01-09-2014 | Gastrointestinal Oncology

Neoadjuvant Chemotherapy with Bevacizumab May Improve Outcome after Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Colorectal Carcinomatosis

Authors: Wim Ceelen, MD, PhD, Yves Van Nieuwenhove, MD, PhD, Dirk Vande Putte, MD, Piet Pattyn, MD, PhD

Published in: Annals of Surgical Oncology | Issue 9/2014

Login to get access

Abstract

Background

In selected patients with colorectal peritoneal carcinomatosis (PC), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) may improve survival. We aimed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population.

Methods

Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin (200–460 mg/m2) or mitomycin C (35 mg/m2). Postoperative outcome and long-term survival were prospectively recorded. The impact of clinical variables on overall survival (OS) was assessed using univariate and Cox multivariate analysis.

Results

Between October 2002 and May 2012, 166 patients were treated with CRS and HIPEC. Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients. Postoperative mortality and major morbidity were 2.4 and 35 %, respectively. Half of the patients received adjuvant chemotherapy. After a median follow-up of 18 months, OS was 27 months (95 % confidence interval 20.8–33.2). On univariate analysis, OS was associated with extent of disease (P < 0.001), neoadjuvant chemotherapy with bevacizumab (P = 0.021), completeness of cytoreduction (CC) (P < 0.001), and adjuvant chemotherapy (P = 0.04), but not with primary disease site, synchronous presentation, or chemoperfusion drug. In multivariate Cox regression, independent predictors of OS were CC (hazard ratio 0.29, P < 0.001) and neoadjuvant therapy containing bevacizumab (hazard ratio 0.31, P = 0.019).

Conclusions

Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab. This regimen merits prospective study in patients with resectable PC of colorectal origin.
Literature
1.
Herszényi L, Tulassay Z. Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci. 2010;14:249–58.PubMed
2.
Peeters M, Price T. Biologic therapies in the metastatic colorectal cancer treatment continuum—applying current evidence to clinical practice. Cancer Treat Rev. 2012;38:397–406.PubMedCrossRef
3.
Klaver YLB, Simkens LHJ, Lemmens V, et al. Outcomes of colorectal cancer patients with peritoneal carcinomatosis treated with chemotherapy with and without targeted therapy. Eur J Surg Oncol. 2012;38:617–23.PubMedCrossRef
4.
Sugarbaker PH, Ryan DP. Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Lancet Oncol. 2012;13:E362–9.PubMedCrossRef
5.
Verwaal VJ, van Ruth S, de Bree E, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21:3737–43.PubMedCrossRef
6.
Ceelen WP. Current management of peritoneal carcinomatosis from colorectal cancer. Minerva Chir. 2013;68:77–86.PubMed
7.
Ceelen W, De Somer F, Van Nieuwenhove Y, Vande Putte D, Pattyn P. Effect of perfusion temperature on glucose and electrolyte transport during hyperthermic intraperitoneal chemoperfusion (HIPEC) with oxaliplatin. Eur J Surg Oncol. In press.
8.
Ceelen WP, Peeters M, Houtmeyers P, Breusegem C, De Somer F, Pattyn P. Safety and efficacy of hyperthermic intraperitoneal chemoperfusion with high-dose oxaliplatin in patients with peritoneal carcinomatosis. Ann Surg Oncol. 2008;15:535–41.PubMedCrossRef
9.
Lemmens VE, Klaver YL, Verwaal VJ, Rutten HJ, Coebergh JWW, de Hingh IH. Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study. Int J Cancer. 2011;128:2717–25.PubMedCrossRef
10.
Konigsrainer I, Horvath P, Struller F, Forkl V, Konigsrainer A, Beckert S. Risk factors for recurrence following complete cytoreductive surgery and HIPEC in colorectal cancer–derived peritoneal surface malignancies. Langenbecks Arch Surg. 2013;398:745–9.PubMedCrossRef
11.
Elias D, Gilly F, Boutitie F, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28:63–8.PubMedCrossRef
12.
Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22:3284–92.PubMedCrossRef
13.
Cavaliere F, De Simone M, Virzi S, et al. Prognostic factors and oncologic outcome in 146 patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: Italian multicenter study S.I.T.I.L.O. Eur J Surg Oncol. 2011;37:148–54.PubMedCrossRef
14.
Passot G, Vaudoyer D, Cotte E, et al. Progression following neoadjuvant systemic chemotherapy may not be a contraindication to a curative approach for colorectal carcinomatosis. Ann Surg. 2012;256:125–29.PubMedCrossRef
15.
Klaver YLB, de Hingh I, Boot H, Verwaal VJ. Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy after early failure of adjuvant systemic chemotherapy. J Surg Oncol. 2011;103:431–4.PubMedCrossRef
16.
Moghaddam SM, Amini A, Morris DL, Pourgholami MH. Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer. Cancer Metastasis Rev. 2012;31:143–62.CrossRef
17.
Retsky MW, Hrushesky WJM, Gukas ID. Hypothesis: primary antiangiogenic method proposed to treat early stage breast cancer. BMC Cancer. 2009;9.
18.
Nasti G, Piccirillo MC, Izzo F, et al. Neoadjuvant FOLFIRI plus bevacizumab in patients with resectable liver metastases from colorectal cancer: a phase 2 trial. Br J Cancer. 2013;108:1566–70.PubMedCentralPubMedCrossRef
19.
Eveno C, Passot G, Goere D, et al. Bevacizumab doubles the early postoperative complication rate after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. In press.
20.
Kesmodel SB, Ellis LM, Lin E, et al. Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol. 2008;26:5254–60.PubMedCrossRef
21.
Chereau E, Lambaudie E, Houvenaeghel G. Morbidity of surgery after neoadjuvant chemotherapy including bevacizumab for advanced ovarian cancer. Int J Gynecol Cancer. 2013;23:1326–30.PubMedCrossRef
22.
van der Pool AE, Marsman HA, Verheij J, et al. Effect of bevacizumab added preoperatively to oxaliplatin on liver injury and complications after resection of colorectal liver metastases. J Surg Oncol. 2012;106:892–7.PubMedCrossRef
23.
Votanopoulos K, Ihemelandu C, Shen P, Stewart J, Russell G, Levine EA. A comparison of hematologic toxicity profiles after heated intraperitoneal chemotherapy with oxaliplatin and mitomycin C. J Surg Res. 2013;179: E133–39.PubMedCentralPubMedCrossRef
24.
Glockzin G, von Breitenbuch P, Schlitt HJ, Piso P. Treatment-related morbidity and toxicity of CRS and oxaliplatin-based HIPEC compared to a mitomycin and doxorubicin-based HIPEC protocol in patients with peritoneal carcinomatosis: a matched-pair analysis. J Surg Oncol. 2013;107:574–8.PubMedCrossRef
Metadata
Title
Neoadjuvant Chemotherapy with Bevacizumab May Improve Outcome after Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Colorectal Carcinomatosis
Authors
Wim Ceelen, MD, PhD
Yves Van Nieuwenhove, MD, PhD
Dirk Vande Putte, MD
Piet Pattyn, MD, PhD
Publication date
01-09-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 9/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-3713-7

Other articles of this Issue 9/2014

Annals of Surgical Oncology 9/2014 Go to the issue

Endocrine Tumors

Pancreastatin Predicts Survival in Neuroendocrine Tumors

Hepatobiliary Tumors

Colorectal Liver Metastases Growth in the Embolized and Non-Embolized Liver After Portal Vein Embolization: Influence of Initial Response to Induction Chemotherapy

Thoracic Oncology

Outcomes of Preoperative Chemotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil Followed by Esophagectomy in Patients with Resectable Node-Positive Esophageal Cancer

Colorectal Cancer

A Retrospective Review of 126 High-Grade Neuroendocrine Carcinomas of the Colon and Rectum

Gastrointestinal Oncology

Morbidity and Mortality Associated with Gastrectomy for Gastric Cancer

Thoracic Oncology

Optimizing Surrogate End Points for Preoperative Systemic Therapies in Non-Small Cell Lung Cancers