12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      A phase II study evaluating the use of concurrent mitomycin C and capecitabine in patients with advanced unresectable pseudomyxoma peritonei

      other

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Pseudomyxoma peritonei (PMP) is a rare neoplastic process characterised by progressive intra-abdominal dissemination of mucinous tumour, and generally considered resistant to systemic chemotherapy. A phase II study in patients with advanced unresectable PMP was undertaken to evaluate the combination of systemic concurrent mitomycin C (7 mg m −2 i.v. on day 1) and capecitabine (1250 mg m −2 b.d. on days 1–14) in a 3-weekly cycle (MCap). Response was determined by semiquantitative assessment of disease volume on serial computed tomographic (CT) scans and serum tumour marker (CEA, CA125, CA19-9) changes at 12 weeks. Between 2003 and 2006, 40 patients were recruited through a national centre for the treatment of peritoneal surface tumours. At baseline, 23 patients had progressive disease and 17 had stable disease. Of 39 assessable patients, 15 (38%, 95% confidence intervals (CIs): 25, 54%) benefited from chemotherapy in the form of either reductions in mucinous deposition or stabilisation of progressive pretreatment disease determined on CT scan. Notably, two patients, originally considered unresectable, following MCap and re-staging underwent potentially curative cytoreductive surgery. Grade 3/4 toxicity rates were low (6%, 95% CIs: 4, 9%). Twenty out of 29 assessed patients (69%, 95% CIs: 51, 83%) felt that their Global Health Status improved during chemotherapy. This is the first trial to demonstrate an apparent benefit of systemic chemotherapy in patients with advanced unresectable PMP.

          Related collections

          Most cited references25

          • Record: found
          • Abstract: found
          • Article: not found

          Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study.

          To compare the response rate, efficacy parameters, and toxicity profile of oral capecitabine with bolus intravenous (IV) fluorouracil plus leucovorin (5-FU/LV) as first-line treatment in patients with metastatic colorectal cancer. We prospectively randomized 605 patients to treatment with oral capecitabine for 14 days every 3 weeks or 5-FU/LV by rapid IV injection daily for 5 days in 4-week cycles. The overall objective tumor response rate among all randomized patients was significantly higher in the capecitabine group (24.8%) than in the 5-FU/LV group (15.5%; P =.005). In the capecitabine and 5-FU/LV groups, median times to disease progression were 4.3 and 4.7 months (log-rank P =.72), median times to treatment failure were 4.1 and 3.1 months (P =.19), and median overall survival times were 12.5 and 13.3 months (P =.974), respectively. Capecitabine, compared with bolus 5-FU/LV treatment, produced a significantly lower incidence (P <.0002) of diarrhea, stomatitis, nausea, and alopecia. Patients treated with capecitabine also displayed lower incidences of grade 3/4 stomatitis and grade 3/4 neutropenia (P <.0001) leading to significantly less neutropenic fever/sepsis. Grade 3 hand-foot syndrome (P <.00001) and grade 3/4 hyperbilirubinemia were the only toxicities more frequently associated with capecitabine than with 5-FU/LV treatment. Oral capecitabine was more active than 5-FU/LV in the induction of objective tumor responses. Time to disease progression and survival were at least equivalent for capecitabine compared with the 5-FU/LV arm. Capecitabine also demonstrated clinically meaningful benefits over bolus 5-FU/LV in terms of tolerability.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy.

            In the past, peritoneal carcinomatosis, regardless of primary tumor type, has always been a lethal condition. Recently, special treatments using cytoreductive surgery with peritonectomy procedures combined with perioperative intraperitoneal chemotherapy have resulted in long-term survival. Appendiceal malignancy with a low incidence of liver and lymph node metastases may be especially appropriate for these aggressive local regional treatments. All patients treated with surgery before January 1999 are included. Patients left with gross residual disease after surgery were not given intraperitoneal chemotherapy, but were later treated with intravenous chemotherapy. The intraperitoneal chemotherapy was given in the perioperative period, starting with mitomycin C at 12.5 mg/m2 for males and 10 mg/m2 for females. For patients whose pathology showed adenomucinosis, intraperitoneal chemotherapy was limited to treatment in the operating theater with heated mitomycin C. Patients with mucinous adenocarcinoma or pseudomyxoma/adenocarcinoma hybrid had, in addition to mitomycin C, five consecutive days of intraperitoneal 5-fluorouracil at 650 mg/m2 instilled in 1-1.5 liters of 1.5% dextrose peritoneal dialysis solution. A complete cytoreduction was defined as tumor nodules <2.5 mm in diameter remaining after surgery. The histopathology categorized the patients as having adenomucinosis, adenomucinosis/carcinomatosis hybrid, or mucinous carcinomatosis. A previous surgical score was used to estimate the extent of previous surgical procedures. The morbidity of treated patients was 27% and the mortality was 2.7%. In a multivariate analysis, prognostic factors for survival included the completeness of cytoreduction (P < .0001), the histopathological character of the appendix malignancy (P < .0001), and the extent of previous surgical interventions (P = .001). Patients with a complete cytoreduction and adenomucinosis by pathology had a 5-year survival of 86%; with hybrid pathology, survival at 5 years was 50%. Incomplete cytoreduction had a 5-year survival of 20% and 0% at 10 years. Cytoreductive surgery and perioperative intraperitoneal chemotherapy can be used to salvage selected patients with peritoneal surface spread of appendiceal primary tumors. Similar strategies for other patients with peritoneal surface malignancy such as peritoneal carcinomatosis from colon or gastric cancer, peritoneal sarcomatosis, or peritoneal mesothelioma should be pursued.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer.

              The aim of this study was to determine the patient's preference for oral UFT/leucovorin (LV) or intravenous (i.v.) 5-fluorouracil (5-FU)/LV chemotherapy in metastatic colorectal cancer and to compare 5-FU exposure with these two treatment options. A total of 37 previously untreated patients with advanced colorectal cancer were randomised to start treatment with either oral UFT 300 mg/m2/day plus oral LV 90 mg/day for 28 days every 5 weeks or i.v. 5-FU 425 mg/m2/day plus LV 20 mg/m2/day for 5 days every 4 weeks. For the second treatment cycle, patients were crossed-over to the alternative treatment regimen. Prior to the first and after the second therapy cycle, patients were required to complete a therapy preference questionnaire (TPQ). The pharmacokinetics of 5-FU were determined by taking blood samples on days 8, 15 or 22 and 28 for UFT and on days 1 and 5 for i.v. 5-FU. 36 patients were eligible. 84% of the patients preferred oral UFT over i.v. 5-FU. After having experienced both treatment modalities, patients indicated taking the medication at home, less stomatitis and diarrhoea, and pill over injection as the most important reasons for their preference. The area under the plasma concentration curve (AUC) for 5-FU after UFT administration was 113 microM x min on day 8, 114 on day 15 and 98 on day 28; the peak levels (Cmax) were 1.2, 1.3 and 1.0 microM, respectively. The AUC for the 5-FU/LV courses was 3083 microM x min for day 1 and 3809 for day 5 (P=0.002). The Cmax was 170.1 and 196.2 microM (P=0.06) and the clearance 2.6 and 1.9 l/min, respectively (P=0.002). Patients with metastatic colorectal cancer clearly preferred oral over i.v. chemotherapy treatment. This choice was most importantly influenced by convenience and toxicity considerations. Although i.v. bolus 5-FU leads to higher peak 5-FU concentrations and AUC values compared with oral UFT, this pharmacokinetic advantage of i.v. 5-FU seems to translate mainly into higher toxicity as seen in large randomised studies comparing oral UFT/LV with i.v. 5-FU/LV. Oral UFT/LV compares favourably with i.v. 5-FU/LV in terms of toxicity and patient's preference and leads to prolonged 5-FU exposure, which is comparable to continuous i.v. 5-FU treatment.
                Bookmark

                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                05 August 2008
                12 August 2008
                19 August 2008
                : 99
                : 4
                : 591-596
                Affiliations
                [1 ]Peritoneal Tumour Service, Department of Surgery, Christie Hospital NHS Foundation Trust Manchester, UK
                [2 ]Department of Medical Statistics, Christie Hospital NHS Foundation Trust Manchester, UK
                [3 ]Department of Radiology, Christie Hospital NHS Foundation Trust Manchester, UK
                [4 ]School of Cancer and Imaging Sciences, University of Manchester Manchester, UK
                [5 ]Department of Clinical Oncology, Christie Hospital NHS Foundation Trust Manchester, UK
                Author notes
                [* ]Author for correspondence: mark.saunders@ 123456christie.nhs.uk
                Article
                6604522
                10.1038/sj.bjc.6604522
                2527821
                18682713
                28fa2685-cc5e-4b9b-8f77-1a407f085b0d
                Copyright 2008, Cancer Research UK
                History
                : 26 February 2008
                : 23 June 2008
                : 30 June 2008
                Categories
                Clinical Studies

                Oncology & Radiotherapy
                capecitabine,chemotherapy,mitomycin c,pseudomyxoma peritonei
                Oncology & Radiotherapy
                capecitabine, chemotherapy, mitomycin c, pseudomyxoma peritonei

                Comments

                Comment on this article