Erlotinib in wild type epidermal growth factor receptor non-small cell lung cancer: A systematic review

Background: Targeting epidermal growth factor receptors (EGFR) is an innovative approach to managing non-small cell lung cancer (NSCLC) which harbors EGFR mutation. However, the efficacy of these agents like erlotinib in patients without the mutation is not known. Methods: This systematic review included Phase III randomized clinical trials that compared single agent erlotinib to other management options in the setting of NSCLC with reported outcome data on patients with EGFR wild type (EGFRWT) tumors. Outcome data include overall survival (OS), progression free survival (PFS) and response rate (RR). Random effects meta-analysis was used to pool outcomes across studies. Results: Three studies met the inclusion criteria. These studies included a total of 2044 patients with outcome data on 674 patients with EGFRWT tumors (33%). Meta-analysis revealed a statistically significant improvement in OS with erlotinib (hazard ratio of 0.780; 95% confidence interval: 0.654-0.930, P = 0.006). Data were not available to perform PFS or RR analysis. The quality of this evidence is considered to be moderate to high. Conclusion: Our study revealed a significant benefit of erlotinib in patient with EGFRWT tumors compared with other approaches. These findings add another therapeutic option to patients generally considered difficult to treat

Is the outcome of childhood acute myeloid leukemia with t(8;21) inferior in Saudi Arabia? A multicenter SAPHOS leukemia group study

Background: Despite the confirmed favorable prognosis of childhood t(8;21) acute myeloid leukemia (AML), recent reports suggest heterogeneity in survival outcomes in this subtype of AML may be influenced by ethnicity. Therefore, we aimed to assess the outcome of childhood t(8;21) AML in an Arab population to evaluate if survival outcomes were inferior and determine the predictive relevance of additional cytogenetic abnormalities. Methods: This multicenter retrospective study analyzed 175 de novo AML children of 14 years of age or younger consecutively diagnosed between January 2005 and December 2012. Survival outcomes were analyzed and patients with t(8;21) were stratified on the basis of karyotype into sole and additional cytogenetic groups. Results: A total of 33 (18.9%) patients had t(8;21) AML. Complete remission (CR) was achieved in 31 (93.9%) patients. The 5-year overall survival, event-free survival, cumulative incidence of relapse (CIR), and remission death rates were 59.9 ± 9.2, 45.6 ± 9.1, 36.4, and 9.1%, respectively. Despite the administration of hematopoietic stem-cell-transplant salvage therapy in first relapse, five out of 11 (45.5%) relapsed patients died of disease. Subanalysis of sole vs. additional cytogenetic abnormalities revealed no significant difference in outcome. Conclusion: In the present study, childhood t(8;21) AML was associated with inferior survival and resistance to salvage therapy compared to reports from international groups. The inferior outcomes were unrelated to additional cytogenetic abnormalities. Further detailed genetic studies are warranted to unmask the biological and clinical differences between racial/ethnic groups. Given the high CR rate of childhood t(8;21) AML, further modification of postremission therapy to improve the CIR rate is needed

Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia in Saudi Arabia: A multi-institutional retrospective national collaborative study

Background: Treatment of childhood acute lymphoblastic leukemia (ALL) has been available in Saudi Arabia (SA) for over 30 years; however, only limited data have been published from there. This study was conducted to establish processes for collaborative data collection and provide clinical characteristics and outcome of children with ALL in SA.Procedure: Clinical data for patients diagnosed from 2004 to 2008 were retrospectively collected at eight institutions and entered remotely into a custom-built database. Statistics regarding clinical and genetic characteristics and treatment outcome were calculated.Results: The 594 evaluable patients had a median age of 4.37 years and 56.4% were boys. Majority of patients had B-precursor ALL while 10.7% had T-ALL. CNS leukemia was present in 5.2% of patients. The distribution of common genetic abnormalities was similar to that reported from western populations, with 24.6% hyperdiploidy, 21% RUNX1-ETV6 positivity, 4.2% BCR-ABL1 positivity, and 2.5% with MLL gene rearrangement. Patients received risk-adapted therapy according to various protocols, although treatment strategies for the majority were similar. Five-year OS, RFS and EFS were 86.9%, 79.1%, and 73.3%, respectively. The OS for patients with pre-B ALL was significantly higher than for T-ALL (88.0% vs. 71.8%; P = 0.019, Log-Rank test). Patients with pre-B ALL categorized as low-risk by NCI/Rome criteria and those with hyperdiploidy had OS of 93.4% and 95.8%, respectively.Conclusions: The characteristics of childhood ALL in SA are similar to those observed in developed countries. Future prospective studies utilizing unified national protocols are needed to further improve the outcome of our patients

Improved outcome for children with acute lymphoblastic leukemia after risk-adjusted intensive therapy: A single-institution experience

Background and objective: Because of the need for more comprehensive information on the least toxic and most effective forms of therapy for children with acute lymphoblastic leukemia (ALL), we reviewed our experience in the treatment of children with ALL at King Faisal Specialist Hospital and Research Centre (KFSH&RC) and King Fahad National Center for Children\u27s Cancer and Research (KFNCCC&R) over a period of 18 years with a focus on patient characteristics and outcome.Methods: During the period of 1981 to 1998, records of children with ALL were retrospectively reviewed with respect to clinical presentation, laboratory findings, risk factors, stratification, therapy and outcome. The protocols used in treatment included 4 local protocols (KFSH 81, 84, 87 and 90), and subsequently, Children\u27s Cancer Group (CCG) protocols, and these were grouped as Era 1 (1981-1992) and Era 2 (1993-1998).Results: Of 509 children with ALL treated during this period, 316 were treated using local protocols and 193 using CCG protocols. Drugs used in Era 1 included a 4-drug induction using etoposid (VP-16) instead of L-asparaginase. Consolidation was based on high dose methotrexate (MTX) 1 g/m(2) and maintenance was based on oral mercaptopurine (6-MP) and MTX with periodic pulses using intravenous teniposide (VM-26), Ara-C, L-asparaginase, adriamycin, prednisone, VP-16 and cyclophosphamide. International protocols were introduced in Era 2, which was also marked by intensification of early treatment, a wider selection of cytoreductive agents, and the alternating use of non-cross-resistant pairs of drugs during the post-remission period. The end-of-induction remission rate improved from 90% in Era 1 to 95% in Era 2, which was of borderline statistical significance (P=.049). The 5-year event-free survival (EFS) improved from 30.6% in Era 1 to 64.2% in Era 2 (P\u3c.001). Improvement in outcome was achieved without any significant increase in morbidity or mortality, due to improvement in both systemic therapy and supportive care. The most important independent prognostic factors were intensity of therapy, poor risk category assignment and CNS disease at diagnosis.Conclusion: Outcome in children with ALL has improved because of intensification of treatment protocols and better supportive care

Improved outcome for children with acute lymphoblastic leukemia after risk-adjusted intensive therapy : A single-institution experience

Background and Objective: Because of the need for more comprehensive information on the least toxic and most effective forms of therapy for children with acute lymphoblastic leukemia (ALL), we reviewed our ex--perience in the treatment of children with ALL at King Faisal Specialist Hospital and Research Centre (KFSH&RC) and King Fahad National Center for Children′s Cancer and Research (KFNCCC&R) over a period of 18 years with a focus on patient characteristics and outcome. Methods: During the period of 1981 to 1998, records of children with ALL were retrospectively reviewed with respect to clinical presentation, laboratory findings, risk factors, stratification, therapy and outcome. The protocols used in treatment included 4 local protocols (KFSH 81, 84, 87 and 90), and subsequently, Children′s Cancer Group (CCG) protocols, and these were grouped as Era 1 (1981-1992) and Era 2 (1993-1998). Results: Of 509 children with ALL treated during this period, 316 were treated using local protocols and 193 using CCG protocols. Drugs used in Era 1 included a 4-drug induction using etoposid (VP-16) instead of L-asparaginase. Consolidation was based on high dose methotrexate (MTX) 1g/m 2 and maintenance was based on oral mercaptopurine (6-MP) and MTX with periodic pulses using intravenous teniposide (VM-26), Ara-C, L-asparaginase, adriamycin, prednisone, VP-16 and cyclophosphamide. International protocols were introduced in Era 2, which was also marked by intensification of early treatment, a wider selection of cytoreductive agents, and the alternating use of non-cross-resistant pairs of drugs during the post-remission period. The end-of-induc--tion remission rate improved from 90% in Era 1 to 95% in Era 2, which was of borderline statistical signifi--cance (P=.049). The 5-year event-free survival (EFS) improved from 30.6% in Era 1 to 64.2% in Era 2 (P< .001). Improvement in outcome was achieved without any significant increase in morbidity or mortality, due to im--provement in both systemic therapy and supportive care. The most important independent prognostic factors were intensity of therapy, poor risk category assignment and CNS disease at diagnosis. Conclusion: Outcome in children with ALL has improved because of intensification of treatment protocols and better supportive care