Malignant mesothelioma (MM) of the pleura or peritoneum is a universally fatal disease attracting an increasing range of medical interventions and escalating healthcare costs.Changes in survival and the factors affecting survival of all patients ever diagnosed with MM in Western Australia over the past five decades and confirmed by the Western Australian Mesothelioma Registry to December 2005 were examined. Sex, age, date and method of diagnosis, site of disease and histological type were recorded. Date of onset of symptoms and performance status were obtained from clinical notes for a sample of cases. Cox regression was used to examine the association of the clinical variables and the 10-yr periods of disease onset with survival after diagnosis.Survival was inversely related to age, being worse for males (hazard ratio (HR) 1.4, 95% CI 1.2-1.6), and those with peritoneal mesothelioma (HR 1.4, 95% CI 1.1-1.7). Patients with sarcomatoid histology had worse prognosis than patients with epithelioid and biphasic histological subtypes. Survival improved after the 1970s and has made incremental improvements since then. Median (interquartile range) survival by decade, from 1960 until 2005, was 64 (0-198), 177 (48-350), 221 (97-504), 238 (108-502) and 301 (134-611) days; ,4 weeks of this apparent improvement can be attributed to earlier diagnosis.With increasing resources and treatment costs for MM over the past 40 yrs, there have been modest improvements in survival but no complete remissions.

Fifty (5%) of 1039 patients with non‐Hodgkin's lymphomas registered on two Southwest Oncology Group clinical trials between 1972 and 1977 developed evidence of central nervous system (CNS) lymphoma. Thirty‐nine patients (3.7%) had leptomeningeal involvement, 10 patients (1%) had focal cerebral involvement and 2 patients (0.1%) had spinal cord compression. Cytologic examination of the cerebrospinal fluid (CSF) was the most reliable diagnostic technique. Patients with diffuse histologies and those with nodular histiocytic lymphoma had the highest incidence of CNS disease. Diffuse histiocytic lymphoma accounted for 22 patients with CNS involvement. Lymphoblastic lymphoma, convoluted type, was found in 6 patients, although in none was the diagnosis established prospectively. Patients who developed CNS lymphoma usually had extranodal disease and systemic symptoms at initial staging (90% stage IV, 54% “B” symptoms). The most commonly involved extranodal sites included the bone marrow (56%), gastrointestinal tract (26%), skin (18%), and lung (14%). CNS lymphoma was observed at all times during the clinical course but was most common in patients with active, poorly controlled disease. In 13 patients (26%), however, CNS lymphoma was the first sign of relapsing lymphoma. Median survival after recognition of CNS lymphoma was 2 months. The incidence of CNS disease was similar for 5 remission induction regimens employed, but maintenance chemotherapy with vincristine, prednisone and parenteral cytosine arabinoside appeared to substantially reduce the incidence of late CNS relapse (1 of 90 patients) compared to maintenance treatment with oral cyclophosphamide in place of cytosine arabinoside (9 of 90 patients, p = 0.02). This study indicates that there is a subgroup of patients with readily identifiable clinical and pathologic features who might benefit from prophylactic therapy to prevent CNS lymphoma.

The combination of paclitaxel and carboplatin for the treatment of advanced TCC is reasonably well tolerated. However, a response proportion considerably lower than that previously reported was noted. In addition, the median survival time of 9 months was less than the survival time previously reported for patients treated with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin. Although our results may reflect enrollment of patients with poor prognostic features, they also call into question the utility of this regimen.

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Malignant melanoma is rapidly increasing in the United States. Metastatic disease responds poorly to currently available chemotherapy. Pyrazine diazohydroxide (PZDH) is a new agent inhibiting DNA synthesis that is active in mouse tumor models and human xenografts and lacks cross resistance with multiple standard agents. In this phase II trial, patients with no prior chemotherapy or immunotherapy for metastatic disease and performance status (SWOG) of 0-1, were treated with pyrazine diazohydroxide at a dose of 100 mg/m2/day by i.v. bolus injection over 5-15 minutes for 5 consecutive days every 6 weeks. There were 23 eligible patients entered on this trial with 74% having PS of 0 and 91% having visceral metastases. There were no confirmed anti-tumor responses. The overall response rate is 0% (95% CI 0%-15%). Median overall survival is six months (95% CI 5-8 months). The most common toxicities were hematologic and consisted of lymphopenia, thrombocytopenia, anemia, and leukopenia. Fatigue. and nausea and vomiting were the next most common toxicities. Pyrazine diazohydroxide by this dose and schedule has insufficient activity in the treatment of disseminated malignant melanoma to warrant further investigation.

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