Taking all these results into consideration, it seems that although the overall outcome for patients with DLBCL is decided by a combination of different clinical and biologic variables, the expression of some of these cell-cycle regulator proteins appears to be specifically associated with the different clinical features of tumors.

No abstract

Cell cycle progression is regulated by the combined action of cyclins, cyclin-dependent kinases (CDKs), and CDK-inhibitors (CDKi), which are negative cell cycle regulators. p27 KIP1 is a CDKi key in cell cycle regulation, whose degradation is required for G1/S transition. In spite of the absence of p27 KIP1 expression in proliferating lymphocytes, some aggressive B-cell lymphomas have been reported to show an anomalous p27 KIP1 staining. We analysed p27 KIP1 expression in a series of Diffuse Large B-cell Lymphoma (DLBCL), correlating it with the proliferative index and clinical outcome, to characterize the implications of this anomalous staining in lymphomagenesis in greater depth. For the above mentioned purposes, an immunohistochemical technique in paraffin-embedded tissues was employed, using commercially available antibodies, in a series of 133 patients with known clinical outcomes. Statistical analysis was performed in order to ascertain which clinical and molecular variables may influence outcome, in terms of disease-free survival (DFS) and overall survival (OS). The relationships between p27 KIP1 and MIB-1 (Ki-67) were also tested. An abnormally high expression of p27 KIP1 was found in lymphomas of this type. The overall correlation between p27 KIP1 and MIB-1 showed there to be no significant relationship between these two parameters, this differing from observations in reactive lymphoid and other tissues. Analysis of the clinical relevance of these findings showed that a high level of p27 KIP1 expression in this type of tumour is an adverse prognostic marker, in both univariate and multivariate analysis. These results show that there is abnormal p27 KIP1 expression in DLBCL, with adverse clinical significance, suggesting that this anomalous p27 KIP1 protein may be rendered non-functional through interaction with other cell cycle regulator proteins. © 1999 Cancer Research Campaign

There is a current unmet medical need for treatment of leptomeningeal metastases (LMD). To analyze the efficacy and safety of systemic temozolomide (TMZ) for first-line treatment of patients with LMD associated with solid tumors, a phase II, non-randomized, multicenter, prospective study was conducted. The planned duration of treatment was a maximum of six cycles (24 weeks) or until unacceptable toxicity was reported. One cycle of oral TMZ (100 mg/m(2) daily) consisted of one week on treatment/one week off treatment for four weeks. The study was stopped early because of poor accrual. Nineteen patients (median age 51(33-72); 32 % male) were enrolled. The LMD source was breast cancer (53 %) and non-small-cell lung cancer (37 %). Previous treatment was chemotherapy (100 %), surgery 74 %, radiotherapy 79 %, and hormone therapy 42 %. The average last dose of TMZ received by patients was 171 mg and only one patient required dose reduction. Three of 19 patients (15.8 %) had clinical benefit and 16 of 19 patients (84.2 %) progressed. Of the two patients completing the study (six cycles, 24 weeks), one had a partial response and the other stable disease. Median survival was 43 days (95 % CI 28.7-57.3); there were 18 deaths. Median TTP was 28 days (95 % CI 14-42). The most common adverse event was vomiting (52.6 %); nine patients (47.4 %) reported at least one serious adverse event but only one episode of thrombocytopenia was drug related. Median Karnofsky score remained at or above 70 % throughout the study, and was 75 % at the end of the study. First-line TMZ was well tolerated, and did not adversely affect the quality of life of patients with LMD. Future studies are needed to verify the efficacy results of this pilot trial.

A total of 170 febrile episodes in neutropenic patients with cancer were randomly assigned to be treated with piperacillin-amikacin or ceftazidime-amikacin. The overall response rates were similar in both groups (68 and 65%, respectively). Response rates for clinicallBy or microbiologicaily documented episodes were 54.5% for piperacillin-amikacin and 58.8% for ceftazidime-amikacin. Response rates for gram-negative bacillary infections were 65 and 73%, respectively. There was also no difference for gram-positive infections (31 and 50%1, respectively). The toxicities were also comparable and consisted of skin rashes, hypokalemia, and diarrhea. Vancomycin was added if the fever persisted 72 h after the beginning of therapy, it increased the response rates to 94% when used with piperacillin-amikacin and 92% when used with ceftazidime plus amikacin. Our results suggest that the combinations show similar global efficacies in the treatment of febrile episodes in cancer patients.