phase 2 study of the combination of gemcitabine and cisplatin in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines with/ without taxanes

Many patients with relapsed metastatic breast cancer are pre-treated with taxanes and anthracyclines, which are usually given in the neoadjuvant/adjuvant setting or as first-line treatment for metastatic disease. The primary objective of this study was to determine the overall response rate for combination treatment with gemcitabine and cisplatin in patients with locally advanced or metastatic breast cancer who had relapsed after receiving one adjuvant/neoadjuvant or first-line metastatic chemotherapy regimen containing an anthracycline with/without a taxane. Secondary endpoints included duration of response, time to progression, one-year survival probability, and toxicity. A single-arm, open-label, phase 2 study conducted at 1 7 investigative sites in Egypt. Treatment consisted of gemcitabine [1250 mg/m[2]] on Days 1 and 8 and cisplatin [70 mg/m[2]] on Day 1 of each 21-day cycle. Treatment continued until disease progression or a maximum of 6 cycles. Of 144 patients all were evaluable for safety and 132 patients were evaluable for efficacy. The overall response rate was 33.3% and 45.5% of the patients with stable disease as their best response. The median time to progression was 5.1 months and the one-year survival probability was 73%. The most common grade 3/4 adverse events were nausea/vomiting [20.1%], neutropenia [19.4%], anemia [13.9%], asthenia [11.1%], diarrhea [9.7%], stomatitis [7.6%], leucopenia [7.6%], and thrombocytopenia [6.2%]. Twelve [8.3%] patients had serious adverse events. The results of this study indicate that gemcitabine and cisplatin were active and generally well tolerated in pretreated patients with locally advanced or metastatic breast cancer

phase II study of gemcitabine combined with vinorelbine as first-line chemotherapy for metastatic breast cancer

There is an unmet need for new combination treatments, especially for aggressive, visceral, and high tumor burden metastatic breast cancer. Gemcitabine [GEM] has shown synergy with vinorelbine [VRL] in preclinical models, and has a toxicity profile that is different from VRL, another recently approved cytotoxic drug that seems to be effective in the treatment of breast cancer. We studied the efficacy and side effects of the GEM-VRL combination as first-line chemotherapy in patients in an openlabel, single arm, phase II study in patients with locally advanced or metastatic breast cancer who had been previously treated with an anthracycline-based regimen in the adjuvant/neoadjuvant setting. Of the 74 patients enrolled, 72 patients were evaluable for the primary treatment outcome [tumor response rates]. Four patients [6%] had a complete response and 26 patients [36%] had a partial response. Nineteen patients [26%] had stable disease. The median time to disease progression was 37 weeks [range, 1 -60 weeks]. Median duration of response was 43 weeks [range, 8.6 to 55 weeks] and one-year survival was 77% [95% confidence interval, 64% to 86%]. Grade 3-4 neutropenia without fever was reported in 10% of patients, thrombocytopenia in 1%, and febrile neutropenia in 11%. The most common clinical grade 3-4 toxicities were nausea [24%] and diarrhea and stomatitis [11% each]. Hospitalizations for adverse events mainly due to anemia, febrile neutropenia, septic shock and hepatic failure occured in 7%. With an overall response rate of 42%, the GEM-VRL combination had promising efficacy and good tolerability in metastatic breast cancer patients

association and clinical impact of PRAME mRNA expression in acute leukemias

PRAME [preferentially expressed antigen of melanoma] has been previously Identified as a melanoma antigen. It encodes an antigen recognized by autologous cytotoxic T lymphocytes. It shows no or very low expression in normal tissues, however a wide range of tumors including haemato-poietic neoplasias express this gene. The aim of this study is to detect PRAME gene expression in acute leukemias and to evaluate its clinical importance. Study and control groups consisted of thirty newly diagnosed cases of acute leukemia [15 AML and 15 ALL cases] and 10 age-matched healthy persons respectively. PRAME mRNA was detected by RT-PCR. Cases were monitored for 6 months and their treatment outcome was classified into responders and non responders. Initially PRAME positive responders were selected for re-evaluation of their PRAME expression by RT-PCR. Cases results in first admission showed that 50% of the studied leukemia cases expressed PRAME of which 66.7% AML cases and 33.3% ALL cases. Although the expression of PRAME was higher in AML than ALL, however the difference was not statistically significant. In particular PRAME was frequently expressed in AML M2 [40%], AML M3 [30%] and ALL L2 [80%], All normal controls did not express any PRAME mRNA transcript. The difference between patients and controls was statistically significant [p=0.00]. NO important correlation was found between PRAME expression, clinical and laboratory data such as age, sex, organomegally, lymphadenopathy, HB and blast%. As regards treatment outcome, PRAME positive cases were consistent more with poor outcome, although statistical companson of both groups did not reach statistical significance. BY reanalyzing PRAME expression in PRAME positive responders [5 cases], it was found that all cases still expressed PRAME mRNA transcript with the exception of one case. Hence a future possibillty to use PRAME as a marker to verify molecular remission and/or predict haematological remission/relapses should be particularly considered. Monitoring the levels of PRAME expression during the course of disease progression is absolutely indicated to postulate its potential as a marker for minimal residual disease. The impact of different treatment approaches on the levels of PRAME expression needs further investigations on a wider scale