Mesothelioma Cancer Treatment With Cytoreductive Surgery And Intraperitoneal Chemotherapy

Cytoreductive Surgery and Intraperitoneal Chemotherapy

In 1988, Antman and colleagues stated that complete surgical removal of MPM was rarely performed and showed no survival benefit (Antman et al. 1988). Only as a combination of complete cytoreductive surgery plus perioperative chemotherapy developed for the treatment of appendiceal and colorectal peritoneal metastases was applied to MPM did treatment outcomes improve (Sugarbaker and Jablonski 1995; Sebbag et al. 2000). 

Vidal-Jove and colleagues 1991 reported favorable results with a curative approach to MPM using cytoreductive surgery including peritonectomy combined with perioperative intraperitoneal chemotherapy (Vidal-Jove et al. 1991). In this report, two cycles of intraperitoneal doxorubicin were used prior to cytoreductive surgery. Histological assessment of the tumor before treatment and at the time of its second appearance indicates a pronounced response of the disease to the effects of intraperitoneal chemotherapy

Pharmacological studies on the potential benefits of intraperitoneal compared to systemic doxorubicin in peritoneal mesothelioma patients are presented. In 1996, Fernandez - Trigo, and Sugarbaker reported the evolution of treatment in seven patients with malignant peritoneal mesothelioma (Sugarbaker and Fernandez-Trigo 1996). The recommended management plan is cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy with cisplatin and then early postoperative intraperitoneal chemotherapy (EPIC) with doxorubicin. 

Long-term survival was reported in four of the seven patients. Complete Cytoreduction is emphasized in this report if long-term benefits are to be achieved. In 2000 at ASCO, Sebbag and colleagues reported 33 patients treated between 1989 and 1999 at The Washington Cancer Institute who underwent cytoreductive surgery and perioperative chemotherapy as new and definitive treatment strategies (Sebbag et al. 2000). 

The median survival since diagnosis in these patients was 31 months with overall survival of 33% and 26% at 3 and 5 years, respectively. The most significant positive predictive factors for survival were complete cytoreduction (p = 0.0002), low initial surgical score (p = 0.0025), female gender (p = 0.0031), and patients who were able to undergo second view surgery (p = 0.0191). Twenty-two of the 33 patients experienced long-term relief from their ascites. 

The morbidity rate was 33.5%, and perioperative mortality was 3%. They concluded that although MPM is a rare disease, progress in its management has taken place. Their survival has been extended, and ascites is successfully palliated. Several long-term survivors were seen, and the selection factors used for these long-term survivors for aggressive treatment strategies were determined. They concluded that MPM is a treatable disease with long-term benefits.

In 1997, Ma and colleagues from the National Cancer Institute, Bethesda, Maryland, reported on nine patients treated between 1993 and 1996 with debulking surgery followed by chemo hyperthermic peritoneal perfusion. Heated intraoperative treatment of cisplatin (Ma et al. 1997). Eight of the nine patients were optimally debulked and had no evidence of disease with an average follow-up of 10 months. 

In 1999, Mongero and colleagues from Columbia Presbyterian Medical Center, New York City, reported three patients undergoing induction IP chemotherapy, CRS, and then HIPEC (Mongero et al. 1999). They concluded that intraoperative hyperthermic peritoneal chemotherapy may play a role in new approaches to the treatment of peritoneal malignancies that were previously unresponsive to traditional systemic chemotherapy regimens.

Also in 1999, Park and colleagues from the National Cancer Institute, Bethesda, Maryland, reported on 18 patients from 3 consecutive Phase I trials (Park et al. 1999). All patients had tumor debulking followed by increased doses of hyperthermic intraperitoneal cisplatin. The Median follow-up after treatment was 19 months (range 2-56) with no surgery-or treatment-related deaths. Overall, morbidity is 24%. 

Nine out of ten patients have a resolution of ascites, and three who develop recurrent ascites regress with a resolution of their ascites. The average progression-free survival is 26 months, and the overall 2-year survival is 80%. The average overall survival is not achieved. These authors conclude that hyperthermic intraperitoneal chemotherapy with cisplatin can be added to aggressive surgical debulking without minimal mortality and morbidity. Compared to historical controls, their patients showed prolonged survival.

The Washington Cancer Institute, National Cancer Institute, and Columbia Presbyterian Hospital mesothelioma treatment centers continued their work over the next two decades. Because of their advanced clinical investigations and those of many other institutions, in 2006 Yan and colleagues conducted a systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the treatment of MPM (Yan et al. 2007). 

They found the seven prospective observational studies available made it possible to assess 240 MPM patients. Average survival ranges from 34 to 92 months. The 1 -, 3 -, and 5-year survival rates were 60-88%, 43-65%, and 29-59%, respectively. Perioperative morbidity varies from 25% to 40% and mortality from 0% to 8%. In 2009, Yan and colleagues conducted a multi-institutional study of 405 patients with MPM treated with CRS plus HIPEC (Yan et al. 2010). 

The average overall survival in this large group of patients was 53 months, and the 3-and 5-year survival rates were 60% and 47%, respectively. Four prognostic variables were independently associated with improved survival in the multivariate analysis. They were epithelial subtype (p < 0.001), absence of lymph node metastasis (p < 0.001), completeness of cytoreduction (p < 0.001), and use of HIPEC (p = 0.002).

Helm and colleagues 2015 conducted another systematic review and meta-analysis (Helm et al. 2015). They were able to collect 20 articles reporting 1047 patients. The median peritoneal cancer index was 19 (range 16-23), and complete cytoreduction was performed in 67% of patients. Survival estimates at 1, 3, and 5 years were 84%, 59%, and 42%, respectively. Perioperative chemotherapy is associated with prolonged survival. Both HIPEC and EPIC are recognized as effective, but there are no conclusions regarding preferred perioperative chemotherapy.

Source

Harvey I. Pass, Nicholas Vogelzang, Michele Carbone - Malignant Mesothelioma_ Pathogenesis, Diagnosis, and Translational Therapies-Springer (2005)
Mary Hesdorffer, Gleneara E. Bates-Pappas - Caring for Patients with Mesothelioma_ Principles and Guidelines-Springer International Publishing (2019)
Bruce W S Robinson, A Philippe Chahinian - Mesothelioma (2002).

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