Alvaro Aguayo

Oral Capecitabine for the Treatment of Hepatocellular Carcinoma, Cholangiocarcinoma, and Gallbladder Carcinoma

The goal of the current study was to evaluate the efficacy and toxicity of capecitabine in patients with nonresectable hepatobiliary carcinoma.

Nonsurgical treatment of hepatocellular carcinoma

Given the poor prognosis of HCC and the therapeutic challenge posed by underlying liver cirrhosis, efforts and resources must be directed towards preventive strategies. Return on the investment in such research is likely to be greater than can be expected from treatment of advanced disease.

Combination therapy with methotrexate, vincristine, polyethylene‐glycol conjugated‐asparaginase, and prednisone in the treatment of patients with refractory or recurrent acute lymphoblastic leukemia

L‐asparaginase in combination with methotrexate has synergistic antileukemic activity in a schedule‐dependent fashion. A new preparation of L‐asparaginase, polyethylene‐glycol conjugated (PEG)‐asparaginase, is a pharmacologically different formulation of L‐asparaginase with distinct properties including a longer half‐life and less immunogenic properties.

Significance of angiogenin plasma concentrations in patients with acute myeloid leukaemia and advanced myelodysplastic syndrome

Human angiogenin is a potent inducer of angiogenesis. The association between angiogenin and cancer progression and poor outcome in solid tumours has been documented, but its significance in leukaemias has not been evaluated. We evaluated plasma angiogenin levels in 101 previously untreated patients with acute myeloid leukaemia (AML) (59 patients) and advanced myelodysplastic syndrome (MDS) (42 patients). Angiogenin levels were significantly higher in AML and advanced MDS patients than in healthy individuals (P < 0·00001). Angiogenin levels were also significantly higher in advanced MDS than in AML (P = 0·001). Higher levels of angiogenin correlated with prolonged survival periods in both AML and advanced MDS patients (P = 0·02 and 0·01 respectively). We found no correlation between angiogenin plasma level and various patient characteristics, including age, performance status, antecedent haematological disorder, haemoglobin, white blood cell and platelet counts, and poor prognosis cytogenetics. There was no significant correlation between angiogenin level and complete remission rate and duration in AML or advanced MDS patients. In multivariate analysis, angiogenin concentration retained its significance as a prognostic factor in AML (P = 0·03), together with age (P = 0·00007) and haemoglobin (P = 0·03).

Plasma hepatocyte growth factor is a prognostic factor in patients with acute myeloid leukemia but not in patients with myelodysplastic syndrome

Hepatocyte growth factor (HGF) is a potent angiogenic factor. The aim of our study was to evaluate plasma HGF levels and their prognostic significance in patients with newly diagnosed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The sandwich enzyme immunoassay technique was used to quantify HGF in stored samples obtained before treatment from patients with AML (59 patients) and MDS (42 patients) treated at The University of Texas MD Anderson Cancer Center. HGF levels were significantly higher in patients with AML or MDS than in healthy individuals (P < 0.0001). Higher HGF levels in both AML and MDS correlated significantly with white blood cell (P = 0.000001 for both groups) and monocyte counts (P = 0.0004 and 0.003, respectively), and with poor performance status (P = 0.03 and 0.001, respectively). Using Cox proportional hazard model and HGF levels as a continuous variable, plasma levels of HGF correlated with shorter survival of AML (P = 0.001), but not MDS (P = 0.34) patients. No significant correlation was observed between HGF levels and complete remission rate or duration. In the multivariate analysis HGF retained its significance as prognostic factor in AML (P = 0.02), along with age (P = 0.0005).

Vascularity, Angiogenesis and Angiogenic Factors in Leukemias and Myelodysplastic Syndromes

Bone marrow microenvironment plays a crucial role in the leukemogenic process. New studies suggest that the bone marrow vascularity changes significantly in the leukemic process and that angiogenic factors play a major role in leukemia and myelodysplasia. However, hematologic malignancies appear to be particularly vulnerable to the effects of angiogenic factors because most of these factors appear to be secreted by hematopoietic cells, and they may have autocrine and paracrine regulatory effects on the hematopoietic system. The use of angiogenesis inhibitors for the treatment of hematologic malignancies is particularly attractive because it may target not only the environment but also the malignant cells.

Clinical relevance of Flt1 and Tie1 angiogenesis receptors expression in B-cell chronic lymphocytic leukemia (CLL)

Angiogenesis, a complex process tightly controlled by several molecules including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) along with their receptors, plays a major role in the growth and metastasis of solid tumors. The expression and production of VEGF and bFGF have been documented in numerous solid tumors and hematopoietic neoplasms. Having recently shown increased expression of cellular VEGF in the leukemic cells of patients with chronic lymphocytic leukemia (CLL) we decided to investigate the expression of angiogenic receptors Flt1 and Tie1. Levels of Tie1 and Flt1 proteins were measured in leukemic cells from 231 patients with B-cell CLL using Western blot analysis and solid-phase radioimmunoassay (RIA). A strong correlation was found between Flt1 and Tie1 levels and white blood cell count (WBC) and absolute lymphocyte counts. Levels of Flt1 but not Tie1 correlated with levels of cellular VEGF. Interestingly, Tie1 correlated well with Rai stage (P=0.04). Flt1 and Tie1 did not correlate with survival, although when we evaluated the patients with early disease (Rai stage 0-II), higher levels of Tie1 but not of Flt1 correlated with worse survival. These data suggest that Tie1 plays a role in the early stages of B-cell CLL and as the disease progresses, the tumor cells become independent from the effects of Tie1. Further studies are now needed to dissect the mechanisms responsible for this phenomenon.

State-of-the-art in the management of chronic myelogenous leukemia in the era of the tyrosine kinase inhibitors: evolutionary trends in diagnosis, monitoring and treatment

The treatment of patients with chronic myeloid leukemia (CML) continues to evolve rapidly as we gain better insights into the best monitoring strategies and as there is experience with the second generation tyrosine kinase inhibitors (TKI). Certain observations about CML and its clinical course remain relevant, such at its triphasic course and the prognostic value of the Sokal and Hasford scores. Other aspects of the disease including the most appropriate clinical monitoring and follow-up strategies and indications for changing therapy are evolving more rapidly. Best practice recommendations for monitoring of response have not only evolved over time but also affected by the availability and reliability of standard cytogenetics, FISH and molecular monitoring. Standard dose imatinib remains the best first-line therapy for most patients with first chronic phase CML. Patient and disease-related factors to evaluate when considering alternatives such as higher doses of imatinib, dasatinib, nilotinib and allogeneic transplant are discussed.

Complete hematologic and cytogenetic response to 2-amino-9-β-D- arabinosyl-6-methoxy-9H-guanine in a patient with chronic myelogeneous leukemia in T-cell blastic phase: A case report and review of the literature

T‐cell lymphoid blastic phase (BP) transformation is rare in chronic myelogenous leukemia (CML). 2‐amino‐9‐β‐D‐arabinosyl‐6‐methoxy‐9H‐guanine (GW506U78), a prodrug of arabinosylguanine (ara‐G), is effective in T‐cell leukemias.

Nonsurgical Treatment of Hepatocellular Carcinoma

While surgical resection and tumor ablation are the preferred therapies for hepatocellular carcinoma (HCC), these are available or appropriate in only a minority of patients. This reflects the usual comorbidity of severe underlying liver disease that either precludes surgery or makes the surgical approach extremely dangerous. Nonetheless, regional control of HCC is highly relevant and many regional strategies have been explored, including hepatic intra-arterial chemotherapy transarterial chemoembolization, lipiodol chemoembolization, radiation therapy, cryosurgery, percutaneous ethanol injection, and radiofrequency ablation. In addition, a variety of systemic chemotherapeutic agents have been tested in HCC, including various combinations of 5-fluorouracil, doxorubicin, epirubicin, etoposide, cisplatin, and mitoxantrone, as well as interferon, tamoxifen, capecitabine, thalidomide, and octreotide. Published data regarding these regional and systemic therapies will be discussed in this review.