Treatment Of Malignant Peritoneal Mesothelioma Research Articles

Peritoneal mesothelioma in a woman who has survived for seven years: a case report

IntroductionMalignant peritoneal mesothelioma is a rare cancer with poor patient survival. Female gender has been identified as a positive prognostic factor. Recently, it has been suggested that the expression of estrogen receptor β in malignant mesothelioma leads to tumor suppression and a better prognosis.Case presentationWe report the case of a 48-year-old Caucasian woman who is alive and disease-free seven years after the initial diagnosis and treatment of malignant peritoneal mesothelioma.ConclusionThis patient's long survival may be attributable to a combination of factors, including minimal disease, complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy plus the estrogen receptor β positivity of the tumor.

Surgical Treatment of Malignant Peritoneal Mesothelioma: Past, Present, and Future

Malignant peritoneal mesothelioma (MPM) is a rare malignancy that arises from the serosal membranes of the abdominal cavity. In 1972, Moertel published a paper characterizing the clinical course of patients afflicted with MPM and the now recognized clinical features associated with tumor progression within the abdominal cavity. 1 Borow first reported the association between asbestos exposure and mesothelioma that same year. 2 Despite the current recognition that MPM is a distinct entity from its pleural variant, progress in the treatment of patients afflicted with MPM has been hampered by several factors. First, it is an extraordinarily rare condition: only 10‐15% of all patients with mesothelioma present with the peritoneal form of the disease, and this translates into approximately 300‐400 cases in the USA annually. As a consequence, throughout the last two decades many clinical trials testing systemic agents for patients with malignant mesothelioma did not distinguish between those with the pleural versus the peritoneal form of disease. 3‐5 Many of these trials included a small number of patients with MPM and for whom no confident conclusions regarding efficacy of the experimental regimen could be made. It is now becoming increasingly recognized that patients with MPM have a distinct disease for which specific therapies should be developed. Another significant feature of MPM that has challenged our ability to understand the contribution of various therapeutic interventions to patient outcome is the remarkable variability in the biology of this condition. In 1973, Rogoff and colleagues reported outcomes in four patients treated at Memorial Sloan‐Kettering Cancer Center in New York using surgical cytoreduction and whole-abdominal radiotherapy. 6 Two of the four patients survived longer than 5 years. Antman and colleagues reported outcomes of 37 patients with MPM treated at the Dana Farber Cancer Institute and the Brigham and Women’s Hospital between 1965 and 1984 and also noted that, while some patients progressed and succumbed rapidly, others survived for many years after treatment. 7 In their series, patients treated after 1982 underwent cytoreduction, placement of an intraperitoneal (IP) catheter, and received between 8‐10 cycles of IP doxorubicin and cisplatin. Subsequent to that 30 Gy of whole-abdominal radiation was administered. In their analysis, patients with smaller tumor burden and female gender had prolonged survival; those with epithelioid tumors did poorly compared with those with other histopathological types. Since that initial description, the use of multimodal therapy using cytoreduction with some form of high-dose regional chemotherapy has become increasingly

Operative morbidity and mortality in 54 consecutive patients undergoing operative cytoreduction and intraperitoneal chemotherapy for peritoneal mesothelioma

15537 Background: The current standard of care for treatment of malignant peritoneal mesothelioma involves operative cytoreduction and intraperitoneal chemotherapy. Most centers favor aggressive operative cytoreduction to maximally resect gross disease, accepting high morbidity and mortality in the range of 25–50% and 1–10%, respectively. In our Phase I-II trials, patients underwent less extensive operative cytoreduction followed by intraperitoneal chemotherapy and radiation. Patients underwent a second-look cytoreduction operation with heated intraoperative intraperitoneal chemotherapy. We hypothesized this would result in lower operative morbidity and mortality with similar survival. Methods: Hospital electronic notes, discharge summaries, laboratory and radiography reports, and oncologist and surgeon office records were retrospectively reviewed to supplement a prospectively collected database. This database followed 54 patients with verified malignant mesothelioma consented for Phase I-II trials between 1997 and 2004. All documented 30-day morbidity and mortality were categorized; patients were not excluded from this analysis if they went off trial. Survival was defined as the time from first-look operation to death or last follow-up. Summary statistics and Kaplan Meier survival estimates were performed using Stata. Results: 54 first- look and 38 second-look operations were performed with 15% and 21% 30-day morbidity, respectively. There was no 30-day mortality. Respiratory (33%) and infectious (40%) complications comprised 73% of the morbidity. The median length of stay was 5 and 6 days for the first- and second-look operations, respectively. The mean length of stay for both operations combined was 13±9 days. Median follow-up was 32 months, with a median survival of 34 months, and 1, 3 and 5 year survival rates of 70%, 50% and 44%, respectively. Median survival for the epithelial subtype was 68 months. Conclusions: A less-aggressive approach to initial operative cytoreduction followed by perioperative chemotherapy and radiation offers similar survival to other equivalently sized trials with lower morbidity and mortality, and shorter total lengths of stay despite two operations. No significant financial relationships to disclose.

Combined Resection, Intraperitoneal Chemotherapy, and Whole Abdominal Radiation for the Treatment of Malignant Peritoneal Mesothelioma

We report a single-institution Phase I or II trial of surgical debulking, intraperitoneal chemotherapy, and immunotherapy followed by whole abdominal radiotherapy in patients with malignant peritoneal mesothelioma. Between 1997 and 2000, 27 patients with malignant peritoneal mesothelioma were enrolled: 23 with epithelial subtype and 4 with sarcomatoid or mixed subtype. The treatment regimen consisted of surgical debulking followed by 4 intraperitoneal courses of cisplatin alternating with 4 courses of doxorubicin, 4 doses of intraperitoneal gamma interferon, a second laparotomy with resection of residual disease plus intraoperative intraperitoneal mitomycin and cisplatin heated to 41 degrees C, and finally whole abdominal radiotherapy. The median overall survival was 70 months with a 3-year survival of 67% (95% confidence interval, 46%-81%). Fourteen patients have died of their disease with a median time to death of 17 months (range, 0.4-71 months) after consenting to treatment. Seven patients are alive without evidence of disease with a median follow-up of 90 months (range, 71-110 months), and 6 are alive with disease with a median follow-up of 86 months (range, 70-106 months). The regimen was well tolerated. There were no patients with Grade III or IV hematological toxicities, 2 patients with Grade III ototoxicity, and 3 patients with Grade III gastrointestinal toxicity. Based on the results of this study, intensive multimodality therapy appears feasible and effective in this group of patients.

Prospective Trial for the Treatment of Malignant Peritoneal Mesothelioma

Malignant peritoneal mesothelioma (MPM) is a rare and often rapidly fatal disease with median survival of 5 to 12 months for untreated cases and 16 months reported after multimodality treatment. We report a prospective clinical treatment study using cytoreductive surgery combined with intraoperative intraperitoneal heated chemotherapy (IPHC) perfusion using mitomycin C for MPM. Twelve patients (11 male with a mean age 51 years) were treated. Seven patients presented with bulky disease and seven with ascites. All underwent exploratory laparotomy with histologically confirmed diagnosis of MPM. Surgical debulking as feasible was performed. Complete gross tumor removal was possible in only one patient. Cytoreduction was followed by a 2-hour closed low-volume IPHC using mitomycin C. One patient died 50 days postoperatively from complications relating to small bowel perforation. Hematologic toxicity of the procedure was minimal. Ascites was controlled in all patients and permanently in 86 per cent of patients presenting with ascites. To date median survival is 34.2 months with median follow-up of 45.2 months. One patient was re-explored for ventral hernia 2 years post-IPHC, had negative peritoneal biopsies, and remains disease-free at 5 years. Given the dismal prognosis associated with MPM the results of treatment with cytoreductive surgery combined with IPHC perfusion are encouraging. The rarity of MPM makes appropriately powered prospective randomized trials unlikely. Therefore, we now offer this approach off protocol; however, further study of this combined modality therapy is warranted.

Intestinal obstruction due to diffuse peritoneal fibrosis at 2 years after the successful treatment of malignant peritoneal mesothelioma with intraperitoneal mitoxatrone (Short communication)

Intestinal obstruction due to diffuse peritoneal fibrosis at 2 years after the successful treatment of malignant peritoneal mesothelioma with intraperitoneal mitoxatrone (Short communication)

Intraperitoneal chemotherapy for malignant peritoneal mesothelioma

4 patients with malignant peritoneal mesothelioma have been treated with intraperitoneal chemotherapy in the Netherlands Cancer Institute in the recent years. 1 patient achieved a complete remission for 36+ months and another patient had a partial remission that lasted for 10 months. Intraperitoneal chemotherapy alone or in combination with other treatment modalities may yield a response rate of 58% with 24% complete remissions in 70 patients reviewed in the literature. Although these data should be considered with caution because of the heterogenicity of the patient group treated, cisplatin-based intraperitoneal chemotherapy seems to be the best available treatment for malignant peritoneal mesothelioma at present.