Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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To determine the role of myeloablative conditioning and unrelated donor (URD) bone marrow transplantation in the treatment of patients with advanced B-cell chronic lymphocytic leukemia (CLL). ⋯ These data demonstrate that lasting remissions can be achieved after URD transplantation in patients with advanced CLL. High TRM suggest that myeloablative conditioning and HLA-mismatched donors should be avoided in future protocols, and it is mandatory to investigate transplant strategies with a lower morbidity and mortality, including the use of nonmyeloablative regimens.
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Editorial Comment
Combined-modality neoadjuvant therapy for rectal cancer.
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Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT tyrosine kinase, which is a target for the kinase inhibitor imatinib. A subset of GISTs, however, contains mutations in the homologous kinase platelet derived growth factor receptor alpha (PDGFRA), and the most common of these mutations is resistant to imatinib in vitro. Little is known of the other types of PDGFRA mutations that occur in GISTs. ⋯ Including our cases, there are 289 reported PDGFRA-mutant GISTs, of which 181 (62.6%) had the imatinib-resistant substitution D842V. However, our findings suggest that more than one third of GISTs with PDGFRA mutations may respond to imatinib and that mutation screening may be helpful in the management of these tumors.
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Clinical Trial
Phase I and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients with advanced malignancies.
This phase I study was undertaken to define the toxicity, pharmacokinetics, pharmacodynamics, maximum tolerated dose (MTD), and clinical activity of CI-1040, a small-molecule inhibitor of the dual-specificity kinases MEK(mitogen-activated protein kinase kinase) -1 and MEK2 , in patients with advanced malignancy. ⋯ CI-1040 was well tolerated at 800 mg BID administered with food. Both target suppression and antitumor activity were demonstrated in this phase I study.