Clin Cancer Res
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Durable complete remission of metastatic renal cell carcinoma (RCC) has rarely been achieved with current treatment modalities. To solve this problem, alternative therapeutic options with high efficacy and minimal side effects are strongly needed. ⋯ Sequential combination gene therapy using MSC/dTRAIL-TK achieved long-term remission of metastatic RCC without noticeable toxicity. Our findings provide an innovative therapeutic approach to completely eradicate metastatic tumors by simple, repeated administrations of MSC/dTRAIL-TK.
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This study was designed to establish the maximum tolerated dose (MTD) and to evaluate tolerability, pharmacokinetics, and antitumor activity of etirinotecan pegol. ⋯ Etirinotecan pegol showed substantial antitumor activity in patients with various solid tumors and a somewhat different safety profile compared with the irinotecan historical profile. The MTD recommended for phase II clinical trials is 145 mg/m(2) q14d or q21d.
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Brentuximab vedotin (SGN-35), an intravenously administered CD30-specific antibody-drug conjugate, has recently been approved by the U. S. Food and Drug Administration for two indications, including (i) patients with Hodgkin lymphoma relapsing after autologous stem-cell transplantation (ASCT), or after two multidrug regimens in patients with Hodgkin lymphoma who are not candidates for ASCT; and (ii) patients with systemic anaplastic large cell lymphoma (ALCL) who failed at least one prior multidrug chemotherapy regimen. ⋯ The complete response rate was equally as impressive, at 34% and 57% for Hodgkin lymphoma and ALCL, respectively. Results like these and from many other upcoming clinical trials, in which brentuximab vedotin is being investigated in the frontline setting, promise to profoundly change how we manage the CD30-positive lymphoproliferative malignancies. The mechanism of action, preclinical antitumor activity, and clinical activity of brentuximab vedotin against Hodgkin lymphoma, ALCL, and other CD30-expressing lymphomas are reviewed.
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HER2-amplified breast cancer is sometimes clinically insensitive to HER2-targeted treatment with trastuzumab. Laboratory models of resistance have causally implicated changes in HER2 expression and activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway. We conducted a prospective tissue acquisition study to determine if there is evidence for these lesions in metastatic tumors that have progressed on trastuzumab-containing therapy. ⋯ In this series of prospectively collected trastuzumab-refractory human breast cancers, loss of HER2 overexpression was rare, whereas activation of the PI3K-AKT pathway through loss of PTEN or PIK3CA mutation was frequently observed.
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To investigate the incidence of FGFR1 amplification in Chinese non-small cell lung cancer (NSCLC) and to preclinically test the hypothesis that the novel, potent, and selective fibroblast growth factor receptor (FGFR) small-molecule inhibitor AZD4547 will deliver potent antitumor activity in NSCLC FGFR1-amplified patient-derived tumor xenograft (PDTX) models. ⋯ This study provides novel epidemiologic data through identification of FGFR1 gene amplification in Chinese NSCLC specimens (particularly squamous) and, importantly, extends the clinical significance of this finding by using multiple FGFR1-amplified squamous lung cancer PDTX models to show tumor stasis or regression effects using a specific FGFR inhibitor (AZD4547). Thus, the translational science presented here provides a strong rationale for investigation of AZD4547 as a therapeutic option for patients with squamous NSCLC tumors harboring amplification of FGFR1.