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ABSTRACT: Novel therapies are needed to improve outcomes in T-cell lymphomas. The authors report the interim results of a prospective multicenter trial evaluating lenalidomide in T-cell lymphomas.
Patients with recurrent and refractory T-cell lymphomas other than mycosis fungoides and untreated patients ineligible for combination chemotherapy were prescribed oral lenalidomide (25 mg daily) on Days 1 to 21 of each 28-day cycle until disease progression, death, or unacceptable toxicity. The primary endpoint was overall response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. The 2-stage design allows for up to 40 patients.
At the time of this interim analysis, 24 patients were enrolled in this study, and 23 were evaluable for response. The median age was 65 years. The overall response rate was 7 (30%) of 23; all were partial responses. Two patients had stable disease for ≥5 cycles. Responses were seen in anaplastic, angioimmunoblastic, and peripheral T-cell unspecified histologies. Median PFS was 96 days (range, 8-696+ days). Median OS was 241 days (range, 8-696+ days). The most common grade 4 adverse event was thrombocytopenia (33%). The most common grade 3 adverse events were neutropenia (21%), febrile neutropenia (17%), and pain not otherwise specified (17%). Rash correlated with response to therapy (P=.003).
In patients with recurrent and refractory T-cell lymphomas, oral lenalidomide monotherapy has clinical activity, and toxicity is consistent with the known safety profile of lenalidomide. Further study of lenalidomide in these diseases is warranted.
Cancer 10/2010; 116(19):4541-8. · 4.77 Impact Factor
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Michael M Vickers,
Toni K Choueiri,
Miranda Rogers,
Andrew Percy, Daygen Finch,
Ivan Zama,
Tina Cheng,
Scott North,
Jennifer J Knox,
Christian Kollmannsberger,
David F McDermott,
Brian I Rini,
Daniel Y Heng
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ABSTRACT: To characterize and evaluate the efficacy of second-line therapy in patients who had progressed on initial anti-vascular endothelial growth factor (VEGF) therapy.
Between 2005 and 2007, patients with mRCC who received second-line therapy after 1st-line VEGF-targeted therapy were identified across 7 cancer centers.
A total of 645 mRCC patients received first-line VEGF-targeted therapy, of which 216 patients received second-line VEGF-targeted therapy (sunitinib, n = 93; sorafenib, n = 80; bevacizumab, n = 11; axitinib, n = 8) or mammalian target of rapamycin (mTOR)-inhibiting agents (temsirolimus, n = 21; everolimus, n = 3). On multivariate analysis, a higher baseline Karnofsky performance status score before first-line therapy predicted which patients were more likely to receive second-line therapy (P <.0001). The median time to treatment failure of second-line therapy was 4.9 months for anti-VEGF therapy and 2.5 months for mTOR inhibitors (P = .014) (HR: 0.52, CI: 0.29-0.91 and HR: 0.495, CI: 0.27-0.9 after adjusting for Memorial Sloan-Kettering Cancer Center prognostic factors and histology, respectively). Overall survival from start of second-line therapy was not significantly different (14.2 vs 10.6 months respectively; P = .38).
Baseline Karnofsky performance status is an independent predictor of receiving second-line targeted therapy. Patients who receive a second-line anti-VEGF drug appear to have a similar overall survival to those who receive a second-line anti-mTOR drug.
Urology 03/2010; 76(2):430-4. · 2.43 Impact Factor
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ABSTRACT: BACKGROUND: We performed a retrospective population-based study to assess the impact of tyrosine kinase inhibitors (TKIs) on overall survival (OS) in patients treated for metastatic renal cell carcinoma (mRCC) in Alberta, Canada and to assess the impact of nephrectomy on OS in patients treated with TKIs. METHODS: We identified 134 patients who began taking a TKI between December 2003 and June 2007 for mRCC in Alberta. We compared survival in this group to that in an earlier cohort of 141 patients treated with interferon-alpha (IFN-alpha) between May 1995 and March 2003. We used the Kaplan-Meier method to determine OS, and we used a Cox proportional hazards model to determine hazard ratios (HRs) and confidence intervals (CIs). We performed multivariate analysis to assess the impact of neprhectomy on OS. RESULTS: Of the 134 patients treated with TKIs, 81 received treatment in the first-line setting, whereas 53 received treatment after prior IFN-alpha therapy. All 141 patients from the IFN-alpha cohort received treatment in the first-line setting. Patients treated with TKIs had an improved OS compared with the IFN-alpha cohort (HR 0.61, 95% CI 0.45-0.83, p = 0.001). The median OS was 18 months in the TKI group and 10 months in the IFN-alpha group. The benefit of TKIs was confined to favourable and intermediate risk groups according to the Memorial Sloan-Kettering Cancer Center prognostic model. Prior nephrectomy was associated with improved OS in the TKI cohort, independent of other prognostic factors. CONCLUSION: Tyrosine kinase inhibitors improve OS compared with IFN-alpha in mRCC. In patients treated with TKIs, prior nephrectomy is associated with improved survival independent of other prognostic variables.
Canadian Urological Association journal = Journal de l'Association des urologues du Canada 09/2009; 3(4):281-289. · 1.24 Impact Factor
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ABSTRACT: The objective of this study was to determine variables that correlate with the survival of patients with extrapulmonary small cell carcinoma (EPSCC).
Medical records of 101 eligible patients with EPSCC who were diagnosed in Saskatchewan from 1971 to 2002 were reviewed. Survival was calculated by using the Kaplan-Meier method. A logistic regression analysis with a backward elimination was carried out to determine prognostic variables that predicted mortality.
The median patient age was 72 years (range, 24-100 years), and the male-to-female ratio was 1.4:1. The primary disease sites were as follows: breast, 9%; gastrointestinal, 20%; genitourinary, 18%; gynecologic, 11%; head and neck, 10%; thymus, 2%; and unknown primary site, 31%. Fifty-one patients had limited disease (LD), and 50 patients had extensive disease (ED). Patients with LD had a median overall survival of 34 months (range, 0.2-276 months) compared with 2 months (range, 0.1-108 months) in patients with ED (P < .0001). Among different primary sites, patients with gynecologic small cell cancer (SCC) had a median survival of 54.4 months, whereas patients with SCC of an unknown primary site had a survival of 2.5 months. Among various variables that were examined with respect to their prognostic importance, an abnormal white blood cell count (odds ratio [OR], 6.9; 95% confidence interval [95% CI], 3.4-14.1), an Eastern Cooperative Oncology Group performance status >2 (OR, 4.5; 95% CI, 2.1-9.9), and ED (OR, 2.7; 95% CI, 1.4-5.0) were found to be correlated significantly with mortality.
The gastrointestinal and genitourinary tracts were the 2 major sites involved by EPSCC in the current series. Survival varied according to the primary sites, and patients with gynecologic tumors had the best prognosis. An abnormal white blood cell count, a poor performance status, and disease extent were important factors in predicting survival.
Cancer 12/2006; 107(9):2262-9. · 4.77 Impact Factor
