Population level survival of patients with chronic myelocytic leukemia in Germany compared to the US in the early 21st century

INTRODUCTION: The advent of tyrosine kinase inhibitors has produced 5-year survival of 90 + % for chronic myelocytic leukemia (CML) patients in clinical trials. However, population level survival has been lower, especially in older patients. Here, we examine survival of patients with CML in Germany and compare it to survival of patients in the United States (US). METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database in the US and 11 cancer registries in Germany. Patients 15–69 years old diagnosed with CML were included in the analysis. Period analysis for 2002–2006 was used to provide the most up-to-date possible estimates of five-year relative survival. RESULTS: Five-year relative survival was 68.7% overall in Germany and 72.7% in the US. Survival was higher in the US for all age groups except for ages 15–39 years, but the difference was only statistically significant for ages 50–59 years (at 67.5% vs 77.7% in Germany and the US, respectively). Survival decreased with age, ranging from 83.1% and 81.9%, respectively, in Germany and the US for patients 15–39 years old to 54.2% and 54.5%, respectively, in patients 65–69 years old. Survival increased between 2002 and 2006 by 12.0% points in Germany and 17.1% points in the US. CONCLUSIONS: Five-year survival estimates were higher in the US than in Germany overall, but the difference was only significant for ages 50–59 years. Survival did not equal that seen in clinical trials for either country, but strong improvement in survival was seen between 2002 and 2006

The MENA leading arbitrators' guide to international arbitration /

"The MENA Leading Arbitrators' Guide to International Arbitration" aims to provide a unique insight into how leading arbitrators of the Middle East and North Africa approach a number of core procedural and substantive law issues in arbitrations seated in the MENA region. Apart from taking the reader through the main procedural milestones of a MENA-seated arbitration, it also deals with some of the key subjects of arbitration in the region, such as the question of arbitrability, the fundamental distinction between institutional and ad hoc arbitration, the powers and duties of arbitrators sitting in the MENA, the role of the national courts in their capacity as curial and supervisory courts in the arbitration, fees and costs in MENA arbitration and the often vexed topic of public policy, to name a few. At the substantive law level, the reader will benefit inter alia from insiders' views on force majeure and hardship in the MENA region. The title also examines specific types and industry sectors of arbitration, starting with free zone arbitration, which has made its debut in the Middle East, investment arbitration and arbitration in construction, oil and gas, maritime, and banking and finance. Finally, the title also features a number of topical contributions on gender and diversity in MENA arbitration.--Publisher

A Phase II Study of Dasatinib in Patients with Chronic Myeloid Leukemia (CML) in Myeloid Blast Crisis Who Are Resistant or Intolerant to Imatinib: First Results of the CA180006 ‘START-B’ Study.

Abstract Dasatinib (BMS-354825) is a novel, oral, multi-targeted kinase inhibitor of BCR-ABL and SRC kinases. Data from a phase I study suggest that dasatinib exhibits potent activity with high hematologic and cytogenetic response rates in CML patients with myeloid blast crisis (MBC) who were imatinib (IM)-resistant (IM-R) or -intolerant (IM-I). Here we report the preliminary results from one Phase II trial (Study CA180006 or ‘START-B’) in MBC, which was initiated in December 2004. This open-label study was carried out in 37 centers worldwide between December 2004 and May 2005. A total of 74 IM-R or IM-I MBC pts were accrued (41 male, median age 56 years [range 21–71]). Preliminary data are currently available on the first 34 pts (29 IM-R and 5 IM-I). Dasatinib was administered orally, at a dose of 70 mg twice daily (BID) in a continuous daily dosing schedule; dose escalation to 100 mg BID was permitted for patients who did not achieve hematologic response and dose reduction to 50 mg and 40 mg BID was allowed in the presence of persistent toxicity. Complete blood counts were performed weekly and bone marrow assessment, including cytogenetic analysis, was performed monthly. Mutations in the BCR-ABL domain were assessed in all pts. Pretreatment characteristics of these 34 pts included: 71% male, median age 54 years (range 21 – 71). Median duration of CML from first diagnosis was 49.3 months (range 5.6 – 215.5). Prior therapy included bone marrow transplant (5 pts, 15%) and interferon (18 pts, 53%). In 44% of pts, the highest IM dose was &amp;gt;600 mg/day and 41% of pts received IM for &amp;gt;3 years. Best responses to IM were complete hematologic response (CHR) in 82% of pts and major cytogenetic response in 39% of pts (complete in 27%, and partial in 12%). At baseline, 35% of pts had a WBC count ≥20 x 103/mm3, 71% had a platelet count &amp;lt;100 103/mm3 and 24% had ≥50% bone marrow blasts. BCR-ABL mutations were documented in 4/10 pts with data currently available. Dasatinib doses were increased in 32% of pts while dose reductions were required in 21% of pts, mostly due to persistent thrombocytopenia. Major hematologic responses were documented in 16/29 (55%) pts with 7 CHR and 9 no evidence of leukemia (CHR without complete recovery of PMN or platelets). There were 13 (45%) cytogenetic responses, including 6 (21%) complete (0% Ph+) and 5 (17%) partial (1 – 35% Ph+). Molecular response data are not yet available. Dasatinib therapy was associated with rapid and profound myelosuppression. PMN &amp;lt;500/mm3 occurred in 59% of pts and platelets &amp;lt;25 x 103 /mm3 in 56% of pts. Non-hematologic toxicities were uncommon and usually grade 1 or 2, with diarrhea in 8 pts, rash in 4 pts, nausea in 3 pts (1 grade 3) and peripheral edema in 3 pts. 4 pts had pleural effusion. In conclusion, preliminary data from this Phase II study provide further evidence of the activity of dasatinib in CML patients with MBC and of its acceptable safety profile. Data on all 74 pts, with a minimum of 6 months follow-up, will be presented at the meeting.</jats:p

Subcutaneous omacetaxine mepesuccinate in imatinib-resistant chronic myeloid leukemia (CML) patients (Pts) with the T315I mutation: Data from an ongoing phase II/III trial

7008 Background: Omacetaxine (OM), a first-in-class cetaxine shows clinical activity against Ph+ CML with a mechanism independent of tyrosine kinase inhibition. Currently available tyrosine kinase inhibitors (TKIs) have no activity against T315I. Methods: Adult Pts with T315I+ CML following TKI failure received OM induction at 1.25 mg/m2 subcutaneous (SC) twice daily (BID) for 14 days every 28 days followed by maintenance at 1.25 mg/m2 SC BID for 7 days every 28 days (maintenance after at least one induction cycle and achievement of hematologic response). Results: 66 pts (39 chronic [CP], 16 accelerated [AP] and 11 blast phase [BP]) have been enrolled. All had failed prior imatinib and 80% failed ≥2 prior TKIs. Median age is 58 yrs. Median disease duration is 58 mos. OM is well tolerated with transient myelosuppression as the primary toxicity. Grade 3/4 non-hematologic events are diarrhea (2%) and fatigue (4%). Efficacy data are available for 44 Pts. In CP Pts, the median number of cycles is 4 (1–22) with 39% having received ≥ 6 cycles of therapy; 64% of Pts have had the T315I clone reduced to below detection limits; the 2-year progression free survival is 70%. Conclusions: Omacetaxine in T315I+ CML Pts results in de-selection of the T315I clone and induces hematologic and cytogenetic responses. [Table: see text] [Table: see text] </jats:p