Improvement in systemic chemotherapy options for advanced cases of bilharzial bladder cancer

Bilharzial bladder cancer is a major health problem in Egypt, as well as some African and Asian countries it represents a distinct clinicopathologic disease. In order to investigate efficacy of chemotherapy in cases with advanced bilharizial bladder cancer as well as different clinicopathologic factors, that may impact response to chemotherapy, we conducted a phase III study, upon 58 patients, over the period from April 1999 to Dec. 2002. The 58 patients had pathologically proven bladder carcinoma on top of previous bilharzial cystitis presenting with either metastatic, inoperable, or recurrent disease. The 55 patient's evalvuable for response, 26 patients were randomized to receive single agent epidoxorubicin, claimed to be most active single agent in cases of bilharzial bladder cancer and the remaining 29 patients received the combination of epidoxorubicin with vincristine alternating with etoposide and ifosfamide. The clinicopathologic characteristics of the two groups were comparable, except for the higher frequency of grade 3 tumors in the combination chemotherapy group. Those who received single agent chemotherapy, had a response in only 4 cases response rate [15.38%] with only 2 cases achieving complete remission, those receiving combination chemotherapy had a response in 11 patients [response rate of 37.9%] with only 2 patients achieving complete responses. In terms of disease control rate [CR+PR+SD] epirubicin had a control rate of 46. 15%, with a mean TDP of 8 months and mean OS of 9 months, versus 62% for those receiving combination treatment with a mean TDP of 7 months and a mean OS. of 9.4 months. The 5 year actuarial PFS rate for patients who have achieved PR and CR in both treatment groups [15 patients] was 20.5%, SE = 5.8. Combination treatment group had a higher PFS of 36.2%, in contrast to 15.4% in the group receiving epidoxorubicin treatment, a difference that proved to be statistically significant [p=0.04]. Patients randomized to receive combination treatment had a higher 5 year overall survival rate of 37.9%, versus 25.5% in patient receiving epidoxorubicin treatment, however, this difference was not statistically significant [p=O.4]. Seventy six percent of patients receiving combination treatment expressed both MDR and p53 versus 33% and 50% respectively for those receiving single agent epidoxorubicin, yet such occurrence had no statistically significant correlation with response, but MOR affected OS and PFS for responding cases. Toxicity from treatment was in the form of vomiting, mucositis, diarrhea, leucopenia, anemia and were all comparable between both groups except for alopecia which was more prominent in those receiving single agent epidoxorubicin Among different clinicopathologic variables only the pathologic cell type seemed to affect response

Prognostic impact of internal tandem duplications in the juxtamembrane domain of FMS-like tyrosine kinase 3 gene [FLT3-ITDs] in patients with de novo acute myeloid leukemia with favorable karyotypes

Acute myeloid leukemia [AML], refer to a group of marrow-based neoplasms that have clinical similarities but distinct morphologic, immunophenotypic and cytogenetic features. The overall annual incidence is 3.4/100, 000. Affects all age groups. The incidence of AML increases with age, with a median of 68 years. in adults, AML accounts for 80% of cases of acute leukemia, At National Cancer institute, Cairo University; AML accounts for approximately 41.5% [349] out of the 840 newly diagnosed cases with acute leukemia registered in the time period between January 2002 and 2003 [1]. Despite improvement in AML diagnosis and therapeutics, most patients die from relapse, even those with favourable karyotypes. Hence the need for employing, other genetic parameters that can predict risk of relapse. Several studies reported the significance of FLT3 as independent marker for clinical outcome in most AML patients. So we conducted a study to investigate the incidence and prognostic impact of FLT3 mutations multantand the ratio between and wild type FLT3 in patients with de novo AML expressing normal or intermediate risk karyotypes. Our study included 60 subjects with newly diagnosed acute leukemia ranging in age from 18 to 60 years; 32 were males and 28 were females they all presented to the medical oncology clinics, National Cancer Institute, Cairo University, during the time period from January 2005 to December 2007. Analysing the association of FLT3 mutations with FAB subtypes and biological characteristics of the 60 AML patients studied showed that 11 had the FLT3/ITD mutation [18.3%]. The patients ranged in age from 18 to 60 years with a median age of 39.5 years the age of patients at presentation was similar in both groups. There was no statistically significant difference in age and sex between the patients harboring mutations in the FLT3 gene and patients with no FLT3 mutation. The majority of FLT3 mutations were detected in patients with M1 9 of 22 [40.9%], M2 5 of 16[31.3%], M4 2 of 7 [22.2%]. Stratifying patients using FAB classification of AML there was a statistically significant difference between the distribution of FLT3/ITD[+] and FLT3/ITD[-] by FAB classification, where FAB classification in FLT3/ITD[+] cases was [M1:7 patients [31.8%], M2: 4 patients [25%] and in FLT3/ITD[-] cases was [M1 15 patient [68.2%], M2 12 patient [75%], M5, M4, MS and M7 22 patients [100%]]. [P value 0.005]. Statistical comparison of laboratory results between FLT3/ ITD [+] and FLT3/ITD [-] revealed that the percentage of bone marrow blasts at day 15 of treatment between the two groups in patients with FLT3/ITD [+] was 28.36 +/- 32.76% denoting resistance to treatment and lack of response, while in the patients with FLT3/ITD [-] was 6.59 +/- 14.59% with a highly significant difference between the two groups [p value 0.005]. However, no difference was reported between the two groups as regard the percent of blasts in the peripheral blood or bone marrow at presentation. The mean value of HB, WBCs in the peripheral blood, the platelet count between the two groups revealed no significant difference between the two groups. Likewise more patients with FLT3/ITD[-] had remission to treatment at day 15 compared to FLT3/ITD[+] patients, however such difference was not statistically different Also, time to relapse was shorter for patients with FLT3/ITD[+] compared to FLT3/ITD[-] with a statistically significant difference between the two groups [p value 0.00 13] Survival analysis showed the ITD[+] patients had a worse DFS, compared to the FLT3/WT patients [95% confidence interval 0.43-5.57] [p value 0.0013], however the median Survival did not show such effect, with median OS of 4.00 months [95% confidence interval 1.92-6.08] for the ITD+ and 3.00 months [95% confidence interval 0.72-5.28] for FLT3/WT [p-value 0.28]. Our data support the previous studies that FLT3/ITD may be a strong prognostic factor in AML patients. and is associated with a high rate of relapse and lower DFS

changing patterns of bilharzial bladder cancer and its treatment outcome, NCI, Cairo University experience

Bilharzial bladder cancer [B.B.C] is a major health problem. 11 Egypt, as well as some African and Asian countries it represents a distinct clinicopathologic disease. Tumors are usually advanced at presentation, they can be either of squamous or transitional cell carcinoma type, on the background of bilharzial cystitis. Bilharzial bladder cancer is a preventable malignancy, through eradication of the schistosomal infestation. Management is mainly surgical, with median 5 years survival about 48%. This article will try to explore clinicopathologic aspects as well as treatment options of such cases