AL Farquharson1, N Pranesh1, G Witham1, R Swindell2, MB Taylor3, AG Renehan1,4, S Rout1, MS Wilson1,ST O’Dwyer1 and MP Saunders*,4,51Peritoneal Tumour Service, Department of Surgery, Christie Hospital NHS Foundation Trust, Manchester, UK; 2Department of Medical Statistics, ChristieHospital NHS Foundation Trust, Manchester, UK; 3Department of Radiology, Christie Hospital NHS Foundation Trust, Manchester, UK

British Journal of Cancer (2008) 99, 591 – 596 (link to article)

The goal of the study was to study the benefits of concurrent Mitomycin C (MMC) and oral capecitabine (Xeloda) treatments in patients with advanced unresectable PMP. Conventionally, it thought that advanced PMP is resistant to systemic chemotherapy. But considering that MMC is a commonly used anti tumor cancer agent in intestinal cancers and HIPEC, that capecitabine is widely used in metastatic colon cancer, that the combination MCap is effective in advanced colorectal cancer, and that a recent report described a PMP patient who responded to capecitabine, this study aims at evaluating the tumor response, survival, toxicity and quality of life in patients receiving MCap chemotherapy for advanced unresectable PMP.

Forty patients were accepted for the clinical trials, 27 had DPAM, 10 had PMCA-I/D, and 3 had PMCA. 17 patients had stable disease and 23 patients had progressive disease. The patients were administered MMC 7mg intravenous injection once a day and 1250 mg oral capecitabine twice a day for 14days. The next cycle of treatments only included oral treatments of 1250mg capecitabine for 14days. In addition, prophylactic anti-emetic (ondansetron) was given along with the MMC injection to treat the nausea and vomiting accompanied by chemotherapy. Patients had at least 12 weeks of treatments. The assessment was run at baseline and every 3 weeks recording the following parameters: performance status, weight, abdominal girth, toxicity, tumor markers (CEA, CA125, CA19-9), CT scans at baseline, 12weeks and 24 weeks, and QOL assessment at baseline, 6 weeks and then every 12 weeks during chemotherapy course.. It must be noted that measurement of the disease volume and response is very difficult and for that the study approached CT assessment with three criteria: (i) overall assessment of the disease volume including mucin; (ii) recording of new disease sites; (iii) the extent of compressive effects of disease on intraperitoneal organs. Decreases in volumes of mucin alone were not recorded as responses.

Overall, out of the 39 assessable patients, 15 (38%) benefited from the chemotherapy regimen, in terms of a reduction in mucus or stopping progression of disease. Two patients, who previously had unresectable disease went on to receive CRS and HIPEC with curative potential. The study does not mention the numbers in relation to histologic type. In general, the overall quality of life remained stable with the exception of the side effects experienced during chemotherapy. The article proposes that for patients experiencing PMP, at least half of them will present with advanced and unresectable PMP. It is recommended that doctors perform a 3-6monthly scan to watch the progression of the disease. A watch and wait approach is recommended for non-progressive disease. If patients are radiologically progressive or become symptomatic, they should be considered for MCap chemotherapy for a 6 month course followed by a rest period. If CT surveillance detects progression, repeat MCap is recommended . Although, there was a reduction in the tumor marker levels after treatment, the study states tumor marker levels did not appear helpful in determining chemotherapy response.