Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for malignant peritoneal mesothelioma: mitomycin versus cisplatin

Our plain-English summary of Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for malignant peritoneal mesothelioma: mitomycin versus cisplatin, by A.U. Blackham, P. Shen, J.H. Stewart, et al (Annals of Surgical Oncology, 2010).

The study

• Authors: A.U. Blackham, P. Shen, J.H. Stewart, G.B. Russell, E.A. Levine
• Journal: Annals of Surgical Oncology
• Published: 2010;17(10):2720-7
• Cited by: 53 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant peritoneal mesothelioma (MPM) is a rare, rapidly fatal disease. Because traditional treatments offer little benefit, there has been increasing interest in cytoreductive surgery (CS) with intraperitoneal hyperthermic chemotherapy (IPHC). The most efficacious chemotherapy regimen is not established. Herein we report clinical outcomes of MPM patients treated with CS and IPHC and contrast results using two chemoperfusates: mitomycin and cisplatin.

Methods: Thirty-four patients were treated for MPM. Following CS, 19 patients underwent IPHC with mitomycin and 15 received cisplatin. Overall survival, disease-free survival, and progression-free survival were compared between the two groups.

Results: Overall survival was 56 and 17% at 3 and 5 years, with median survival of 40.8 months. Those perfused with cisplatin were more likely to be alive at 1, 2, and 3 years (P < 0.05, 0.05, and 0.04, respectively). Median survival for mitomycin and cisplatin was 10.8 and 40.8 months, respectively (P = 0.22). Median disease-free survival and progression-free survival were 10.3 and 9.1 months, respectively. There was a trend toward improved disease-free and progression-free survival using cisplatin.

Conclusions: CS with IPHC is a promising modality for patients with MPM, and clinical outcomes appear to be improved using cisplatin. We recommend using high-dose intraperitoneal cisplatin following cytoreductive surgery when treating malignant peritoneal mesothelioma.

In plain English

This retrospective study from Wake Forest University Baptist Medical Center reviewed 38 patients with malignant peritoneal mesothelioma (mesothelioma of the abdominal lining). They were treated between August 1993 and August 2008 with surgery to remove tumor, followed by heated chemotherapy circulated through the abdomen. The study compared two drugs, mitomycin and cisplatin. The article did not report the patients' asbestos exposure. Among the 34 patients in the survival analysis, median survival was 40.8 months, and 61%, 56% and 17% were alive at 1, 3 and 5 years. Median survival was 10.8 months for the 19 mitomycin patients and an estimated 40.8 months for the 15 cisplatin patients. That difference was not statistically significant (P = 0.22). At 1 year, 9 of 19 mitomycin patients (47%) and 12 of 15 cisplatin patients (80%) were alive (P = 0.05). Disease-free and progression-free survival did not differ significantly between the drugs. The authors noted small groups, a 15-year span with four surgeons, and shorter follow-up for cisplatin patients. They concluded that they consider high-dose cisplatin the agent of choice.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study (chart review) at a single institution comparing two chemotherapy drugs used with cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC); cases drawn from a prospectively maintained database
• Who was studied: 38 patients with biopsy-proven malignant peritoneal mesothelioma treated at Wake Forest University Baptist Medical Center, Winston-Salem, NC, between August 1993 and August 2008. There were 45 procedures in total. The overall survival analysis included 34 patients: 19 given mitomycin and 15 given cisplatin. Four patients who had mitomycin and then cisplatin at a second procedure were left out of that analysis. Mean age was 54.9 years; the male-to-female ratio was 2:1; 85% had the epithelial subtype and 12% the biphasic subtype.
• Exposure: Not asbestos. The comparison was between two chemotherapy drugs given after cytoreductive surgery: 30 to 40 mg mitomycin, or 250 mg/m2 cisplatin (with sodium thiosulfate). The drug was heated and circulated through the abdominal (peritoneal) cavity for 60 to 120 minutes. The article does not report the patients' asbestos exposure.
• Main results:
  • Median overall survival for all 34 patients was 40.8 months.
  • Overall survival for all patients was 61% at 1 year, 56% at 3 years and 17% at 5 years.
  • Median survival was 10.8 months with mitomycin and 40.8 months with cisplatin. The difference favored cisplatin but was not statistically significant (P = 0.22).
  • The 40.8-month median survival for the cisplatin group is an estimate, because that group's true median survival had not yet been reached.
  • At 1 year, 9 of 19 (47%) mitomycin patients and 12 of 15 (80%) cisplatin patients were alive (P = 0.05).
  • At 3 years, survival was 42% in the mitomycin group versus 80% in the cisplatin group (P = 0.04).
  • Disease-free survival was measured in the 26 patients counted as disease free after surgery (R0/1 or R2a resection). The median was 10.3 months overall: 8.3 months with mitomycin and 10.6 months with cisplatin (P = 0.36).
  • In the 12 patients left with residual disease, median progression-free survival was 9.1 months: 9.1 months with mitomycin and 11.7 months with cisplatin (P = 0.43). Neither disease-free nor progression-free survival differed significantly between the drugs.
  • Among patients disease free after surgery, survival at 1 to 3 years was 91% with cisplatin (n = 11) versus 45% with mitomycin (n = 11). This was not statistically significant (P = 0.09).
  • Among patients left with residual disease, survival did not differ between the two drugs (P = 0.87).
  • Two deaths in the mitomycin group were directly linked to postoperative complications, one from respiratory failure and one from neutropenic sepsis. There were no postoperative deaths in the cisplatin group.
  • All four patients with biphasic mesothelioma did very poorly. Three died within months of surgery, with a median survival of 2.4 months, and one survived 26.9 months.
• The authors' conclusion: The authors concluded that they currently consider high-dose cisplatin the agent of choice for heated intraperitoneal chemotherapy after cytoreductive surgery for malignant peritoneal mesothelioma. They noted that the overall survival difference did not reach statistical significance and that many more studies are needed.
• Limitations the authors state:
  • The groups were small, so one or two deaths changed the overall analysis dramatically.
  • Patients were treated over 15 years by four surgeons, so improving technique could favor more recent patients. However, the authors found no significant difference in survival when patients were split into thirds by date.
  • Follow-up was much shorter for the cisplatin patients (median 1.9 years) than for the mitomycin patients (median 6 years).
  • Postoperative disease status was not significantly different between the groups but trended better in the cisplatin patients.
  • The mitomycin group had more patients with biphasic mesothelioma, a subtype with poorer prognosis (three versus one).

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, Chemotherapy, Peritoneal Mesothelioma, Cisplatin, Overall Survival, Disease-Free Survival, Progression-Free Survival, Median Survival.

Related studies

• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)
• Malignant peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is GLUT1 expression a major prognostic factor? A preliminary study — J. Hommell-Fontaine, S. Isaac, et al. (2013)
• A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy — J.M. Baumgartner, T.G. Kwong, et al. (2016)
• Efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in the management of malignant ascites — R.W. Randle, K.R. Swett, et al. (2014)
• Outcomes of Cytoreductive Surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients older than 70 years; survival benefit at considerable morbidity and mortality — K.I. Votanopoulos, N.A. Newman, et al. (2013)

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