Publications by authors named "Rachid C Baz"

15 Publications

  • Page 1 of 1

Lactate Dehydrogenase B and Pyruvate Oxidation Pathway Associated With Carfilzomib-Related Cardiotoxicity in Multiple Myeloma Patients: Result of a Multi-Omics Integrative Analysis.

Front Cardiovasc Med 2021 29;8:645122. Epub 2021 Apr 29.

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, United States.

Multiple myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), an irreversible proteasome inhibitor being used to treat relapsed and refractory MM, has been associated with cardiotoxicity, including heart failure. We hypothesized that a multi-omics approach integrating data from different omics would provide insights into the mechanisms of CFZ-related cardiovascular adverse events (CVAEs). Plasma samples were collected from 13 MM patients treated with CFZ (including 7 with CVAEs and 6 with no CVAEs) at the University of Florida Health Cancer Center. These samples were evaluated in global metabolomic profiling, global proteomic profiling, and microRNA (miRNA) profiling. Integrative pathway analysis was performed to identify genes and pathways differentially expressed between patients with and without CVAEs. The proteomics analysis identified the up-regulation of lactate dehydrogenase B (LDHB) [fold change (FC) = 8.2, = 0.01] in patients who experienced CVAEs. The metabolomics analysis identified lower plasma abundance of pyruvate (FC = 0.16, = 0.0004) and higher abundance of lactate (FC = 2.4, = 0.0001) in patients with CVAEs. Differential expression analysis of miRNAs profiling identified mir-146b to be up-regulatein (FC = 14, = 0.046) in patients with CVAE. Pathway analysis suggested that the pyruvate fermentation to lactate pathway is associated with CFZ-CVAEs. In this pilot multi-omics integrative analysis, we observed the down-regulation of pyruvate and up-regulation of LDHB among patients who experienced CVAEs, suggesting the importance of the pyruvate oxidation pathway associated with mitochondrial dysfunction. Validation and further investigation in a larger independent cohort are warranted to better understand the mechanisms of CFZ-CVAEs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.645122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116486PMC
April 2021

Multiple myeloma presenting as an intramedullary spinal cord tumor: a case report and review of the literature.

J Med Case Rep 2020 Oct 16;14(1):189. Epub 2020 Oct 16.

Department of Neurosurgery, University of South Florida, Tampa, FL, USA.

Background: Extramedullary disease in multiple myeloma often portends a worse diagnosis. In approximately 1% of cases, multiple myeloma may metastasize to the central nervous system as either leptomeningeal involvement or an intracranial, intraparenchymal lesion. Spinal cord metastases, however, are exceedingly rare. We present a case of spinal cord multiple myeloma as well as a literature review of reported cases.

Case Presentation: A 66-year-old African American man with multiple myeloma presented with acute midthoracic pain and lower extremity paresis and paresthesia. Magnetic resonance imaging of the spine revealed two contrast-enhancing intramedullary enhancing lesions in the T1-T2 and T6-T7 cord. Resection with biopsy yielded a diagnosis of metastatic multiple myeloma.

Conclusion: To date, only six cases of extramedullary disease to the spinal cord in patients with multiple myeloma have been reported, including our patient's case. In all cases, neurologic deficit was observed at presentation, and magnetic resonance imaging of the spine revealed an intramedullary, homogeneously enhancing lesion. Current evidence suggests worse prognosis in patients with extramedullary disease to the central nervous system, and treatment paradigms remain debatable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13256-020-02496-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566029PMC
October 2020

Waldenström Macroglobulinemia: Review of Pathogenesis and Management.

Clin Lymphoma Myeloma Leuk 2017 05 7;17(5):252-262. Epub 2017 Mar 7.

Division of Hematology, Oncology, Blood, and Marrow Transplantation, Department of Medicine, University of Arizona, Tucson, AZ. Electronic address:

Waldenström macroglobulinemia (WM) is a low-grade B-cell clonal disorder characterized by lymphoplasmacytic bone marrow involvement associated with monoclonal immunoglobulin M. Although WM remains to be an incurable disease with a heterogeneous clinical course, the recent discovery of mutations in the MYD88 and CXCR4 genes further enhanced our understanding of its pathogenesis. Development of new therapies including monoclonal antibodies, proteasome inhibitors, and Bruton tyrosine kinase inhibitors have made the management of WM increasingly complex. Treatment should be tailored to the individual patient while considering many clinical factors. The clinical outcomes are expected to continue to improve, given the emergence of novel therapeutics and better understanding of the underlying pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clml.2017.02.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413391PMC
May 2017

Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma.

Blood 2016 05 1;127(21):2561-8. Epub 2016 Mar 1.

Multiple Myeloma Program, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY; and.

Pomalidomide and low-dose dexamethasone (PomDex) is standard treatment of lenalidomide refractory myeloma patients who have received >2 prior therapies. We aimed to assess the safety and efficacy of the addition of oral weekly cyclophosphamide to standard PomDex. We first performed a dose escalation phase 1 study to determine the recommended phase 2 dose of cyclophosphamide in combination with PomDex (arm A). A randomized, multicenter phase 2 study followed, enrolling patients with lenalidomide refractory myeloma. Patients were randomized (1:1) to receive pomalidomide 4 mg on days 1 to 21 of a 28-day cycle in combination with weekly dexamethasone (arm B) or pomalidomide, dexamethasone, and cyclophosphamide (PomCyDex) 400 mg orally on days 1, 8, and 15 (arm C). The primary end point was overall response rate (ORR). Eighty patients were enrolled (10 in phase 1 and 70 randomized in phase 2: 36 to arm B and 34 to arm C). The ORR was 38.9% (95% confidence interval [CI], 23-54.8%) and 64.7% (95% CI, 48.6-80.8%) for arms B and C, respectively (P = .035). As of June 2015, 62 of the 70 randomized patients had progressed. The median progression-free survival (PFS) was 4.4 (95% CI, 2.3-5.7) and 9.5 months (95% CI, 4.6-14) for arms B and C, respectively (P = .106). Toxicity was predominantly hematologic in nature but was not statistically higher in arm C. The combination of PomCyDex results in a superior ORR and PFS compared with PomDex in patients with lenalidomide refractory multiple myeloma. The trial was registered at www.clinicaltrials.gov as #NCT01432600.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2015-11-682518DOI Listing
May 2016

Phase I Study of Anti-GM2 Ganglioside Monoclonal Antibody BIW-8962 as Monotherapy in Patients with Previously Treated Multiple Myeloma.

Oncol Ther 2016 2;4(2):287-301. Epub 2016 Nov 2.

Kyowa Kirin Pharmaceutical Development, Inc., Princeton, NJ USA.

Introduction: BIW-8962 is a monoclonal antibody to GM2 ganglioside that shows preclinical activity towards multiple myeloma (MM) cell lines and in animal models bearing MM xenografts. The objective of this study was to determine the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, potential immunogenicity, and preliminary clinical efficacy of BIW-8962 in patients with heavily pretreated MM.

Methods: Patients ( = 23) received escalating doses of BIW-8962 (0.03-3 mg/kg) intravenously every 2 weeks in phase Ia. The highest anticipated dose (10 mg/kg) was not tested and the study was discontinued without proceeding to phases Ib and II.

Results: The MTD of BIW-8962 was not established and BIW-8962 was relatively well tolerated. No pattern of consistent toxicity could be inferred from treatment-related AEs grade ≥3 and only two dose-limiting toxicities were recorded (atrial thrombosis + cardiomyopathy and chest pain, respectively). In the efficacy evaluable population ( = 22), no patient had a response (complete or partial) and 16 (72.7%) had a best response of stable disease, which was generally not durable.

Conclusion: BIW-8962 did not show evidence of clinical activity. The study was therefore stopped and further development of BIW-8962 in MM was halted.

Funding: This work was funded by Kyowa Kirin Pharmaceutical Development, Inc.

Trial Registered: ClinicalTrials.gov identifier, NCT00775502.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40487-016-0034-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315068PMC
November 2016

A comparison of salvage infusional chemotherapy regimens for recurrent/refractory multiple myeloma.

Cancer 2015 Oct 6;121(20):3622-30. Epub 2015 Jul 6.

Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Background: Despite the impact of proteasome inhibitors and immunomodulatory agents, infusional chemotherapy regimens continue to be used for patients with multiple myeloma. To the authors' knowledge, contemporary data regarding salvage chemotherapy regimens are sparse, with no direct comparisons.

Methods: The authors performed a single-institution study comparing 3 salvage chemotherapy regimens in 107 patients with recurrent/refractory multiple myeloma: dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) in 52 patients; bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide (VTD-PACE) in 22 patients; and cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) in 33 patients.

Results: Differences between treatment groups existed, including higher baseline creatinine for patients treated with CVAD (P<.001) and greater prior use of infusional chemotherapy for those receiving VTD-PACE (P<.001). There was no significant difference in response noted among the 3 regimens: 55% overall (P = .18). For the intent-to-transplant population, a similar percentage were successfully bridged to transplant without further therapy (62%; P = .9). There was no difference in survival observed across the 3 regimens, with an overall median progression-free survival of 4.5 months (95% confidence interval, 3.6-5.5 months [P = .8]) and a median overall survival of 8.5 months (95% confidence interval, 6.1-11 months [P = .8]). Furthermore, there was no statistically significant difference noted among clinically relevant adverse events, although there was a suggestion of fewer adverse events with DCEP. Patients treated with the intent to transplant had superior outcomes for response (odds ratio, 3.40; P = .01), progression-free survival (hazard ratio, 0.28; P<.001), and overall survival (hazard ratio, 0.19; P<.001).

Conclusions: The 3 salvage regimens demonstrated similar responses, survival, and adverse events. Given the short response durations observed in the recurrent/refractory disease setting, infusional chemotherapy is best suited for cytoreduction before more definitive therapy is administered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.29533DOI Listing
October 2015

Phase I trial of bortezomib (PS-341; NSC 681239) and "nonhybrid" (bolus) infusion schedule of alvocidib (flavopiridol; NSC 649890) in patients with recurrent or refractory indolent B-cell neoplasms.

Clin Cancer Res 2014 Nov 23;20(22):5652-62. Epub 2014 Sep 23.

Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and Massey Cancer Center and.

Purpose: This phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, Waldenstrom macroglobulinemia, and mantle cell lymphoma).

Experimental Design: Patients received bortezomib (intravenous push), followed by alvocidib (1-hour infusion), on days 1, 4, 8, and 11 of a 21-day treatment cycle. Patients experiencing responses or stable disease continued on treatment at the investigator's discretion. A standard 3+3 dose-escalation design was used to identify the MTD based on DLTs, and pharmacokinetic and pharmacodynamic studies were conducted.

Results: A total of 44 patients were enrolled, with 39 patients assessed for response. The MTD was established as 1.3 mg/m(2) for bortezomib and 40 mg/m(2) for alvocidib. The most common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common nonhematologic toxicities included diarrhea, fatigue, and sensory neuropathy. Three complete remissions (8%) and 10 partial remissions (26%) were observed for a total response rate of 33%. Pharmacokinetic findings with the current dosing regimen were consistent with the comparable literature and the hybrid dosing regimen. Pharmacodynamic study results did not correlate with clinical responses.

Conclusions: The combination of bortezomib and alvocidib is tolerable, and an MTD has been established for this schedule. The regimen appears to be efficacious in patients with relapsed/refractory multiple myeloma or indolent non-Hodgkin lymphoma. As the nonhybrid regimen is less cumbersome than the previous hybrid dosing schedule regimen, the current schedule is recommended for successor studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-14-0805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233160PMC
November 2014

Quantification of peptides from immunoglobulin constant and variable regions by LC-MRM MS for assessment of multiple myeloma patients.

Proteomics Clin Appl 2014 Oct 15;8(9-10):783-95. Epub 2014 Sep 15.

Molecular Oncology and Proteomics, Moffitt Cancer Center, Tampa, FL, USA.

Purpose: Quantitative MS assays for Igs are compared with existing clinical methods in samples from patients with plasma cell dyscrasias, for example, multiple myeloma (MM).

Experimental Design: Using LC-MS/MS data, Ig constant region peptides, and transitions were selected for LC-MRM MS. Quantitative assays were used to assess Igs in serum from 83 patients. RNA sequencing and peptide-based LC-MRM are used to define peptides for quantification of the disease-specific Ig.

Results: LC-MRM assays quantify serum levels of Igs and their isoforms (IgG1-4, IgA1-2, IgM, IgD, and IgE, as well as kappa (κ) and lambda (λ) light chains). LC-MRM quantification has been applied to single samples from a patient cohort and a longitudinal study of an IgE patient undergoing treatment, to enable comparison with existing clinical methods. Proof-of-concept data for defining and monitoring variable region peptides are provided using the H929 MM cell line and two MM patients.

Conclusions And Clinical Relevance: LC-MRM assays targeting constant region peptides determine the type and isoform of the involved Ig and quantify its expression; the LC-MRM approach has improved sensitivity compared with the current clinical method, but slightly higher inter-assay variability. Detection of variable region peptides is a promising way to improve Ig quantification, which could produce a dramatic increase in sensitivity over existing methods, and could further complement current clinical techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prca.201300077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302417PMC
October 2014

Phase II study of pegylated liposomal doxorubicin, low-dose dexamethasone, and lenalidomide in patients with newly diagnosed multiple myeloma.

Am J Hematol 2014 Jan;89(1):62-7

Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Our previous phase I/II trial of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone, and lenalidomide in patients with relapsed and refractory myeloma showed an overall response rate of 75%, with 29% achieving ≥ VGPR. Here, we investigated this combination (PLD 30 or 40 mg/m(2) intravenously, day 1; dexamethasone 40 mg orally, days 1-4; lenalidomide 25 mg orally, days 1-21; administered every 28 days) in a phase II study in patients with newly diagnosed symptomatic multiple myeloma to determine its efficacy and tolerability (ClinicalTrials.gov NCT00617591). At best response, patients could proceed with high-dose melphalan or with maintenance lenalidomide and dexamethasone. In 57 patients, we found that the overall response rate and rate of very good partial response and better on intent-to-treat, our primary endpoints, were 77.2% and 42.1%, respectively, with responses per the International Myeloma Working Group. Median progression-free survival was 28 months (95% CI 18.1-34.8), with 1- and 2-year overall survival rates of 98.1 and 79.6%. During induction, grade 3/4 toxicities were neutropenia (49.1%), anemia (15.8%), thrombocytopenia (7%), fatigue (14%), febrile neutropenia (8.8%), and venous thromboembolic events (8.8%). During maintenance, grade 3/4 toxicities were mainly hematologic. We found this combination to be active in patients with newly diagnosed myeloma, with results comparable to other lenalidomide-based induction strategies without proteasome inhibition. In addition, maintenance therapy with lenalidomide was well tolerated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.23587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522918PMC
January 2014

Effects of a brief multimedia psychoeducational intervention on the attitudes and interest of patients with cancer regarding clinical trial participation: a multicenter randomized controlled trial.

J Clin Oncol 2012 Jul 21;30(20):2516-21. Epub 2012 May 21.

Moffitt Cancer Centerand University of South Florida, Tampa, FL, USA.

Purpose: The negative attitudes of patients with cancer regarding clinical trials are an important contributor to low participation rates. This study evaluated whether a brief psychoeducational intervention was effective in improving patients' attitudes as well as their knowledge, self-efficacy for decision making, receptivity to receiving more information, and general willingness to participate in clinical trials.

Patients And Methods: A total of 472 adults with cancer who had not been asked previously to participate in a clinical trial were randomly assigned to receive printed educational information about clinical trials or a psychoeducational intervention that provided similar information and also addressed misperceptions and concerns about clinical trials. The primary (attitudes) and secondary outcomes (knowledge, self-efficacy, receptivity, and willingness) were assessed via patient self-report before random assignment and 7 to 28 days later.

Results: Patients who received the psychoeducational intervention showed more positive attitudes toward clinical trials (P = .016) and greater willingness to participate (P = .011) at follow-up than patients who received printed educational information. Evidence of an indirect effect of intervention assignment on willingness to participate (estimated at 0.168; 95% CI, 0.088 to 0.248) suggested that the benefits of psychoeducation on willingness to participate were explained by the positive impact of psychoeducation on attitudes toward clinical trials.

Conclusion: A brief psychoeducational intervention can improve the attitudes of patients with cancer toward clinical trials and thereby increase their willingness to participate in clinical trials. Findings support conducting additional research to evaluate effects of this intervention on quality of decision making and rates of participation among patients asked to enroll onto therapeutic clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2011.39.5186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577714PMC
July 2012

Human immunodeficiency virus (HIV)-negative plasmablastic lymphoma: a single institutional experience and literature review.

Leuk Res 2011 Dec 12;35(12):1571-7. Epub 2011 Jul 12.

Department of Hematology and Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder. HIV-negative PBL has not been extensively reported. Nine HIV-negative PBL patients evaluated at Moffitt Cancer Center were studied. Eight patients had extranodal diseases. All patients were treated with CHOP or hyper-CVAD. Responses were observed in 8 cases (7 complete, 1 partial responses). Four patients underwent consolidation with autologous hematopoietic stem cell transplant (HSCT) in first complete remission (CR1). At median follow-up of 23.9 months, 7 patients were alive and 5 were disease-free. Aggressive induction chemotherapy and consolidation with autologous HSCT in CR1 might be considered for patients with HIV-negative PBL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2011.06.023DOI Listing
December 2011

Leptomeningeal myeloma as the sole manifestation of relapse: an unusual presentation.

Am J Med Sci 2010 Jan;339(1):81-2

Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.

We report a case of a 57-year-old African American male patient with standard risk (IIIA) IgA kappa multiple myeloma. This patient presented with neurologic complaints (manifesting as generalized muscle weakness and swallowing dysfunction associated with a poor cough reflex) 10 months after achieving a very good partial remission and without evidence of systemic progression. Examination of the cerebrospinal fluid revealed leptomeningeal involvement. Very little is known about the mechanisms of myelomatous spread to the leptomeninges, a very rare event, and the presentation of this case could raise awareness of this rare complication in those involved in caring for patients with multiple myeloma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAJ.0b013e3181b61145DOI Listing
January 2010

An association between renal cell carcinoma and multiple myeloma: a case series and clinical implications.

BJU Int 2008 Mar 26;101(6):712-5. Epub 2007 Oct 26.

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Objective: To describe an association between renal cell carcinoma (RCC) and multiple myeloma (MM) in patients with both disorders, and suggest possible explanations for the association.

Patients And Methods: We retrospectively reviewed the records of patients with MM and RCC at the Cleveland Clinic between 1990 and 2005, and identified 1100 with MM, 2704 with RCC and eight with concomitant MM and RCC. The medical records of these eight patients were reviewed.

Results: In four of the eight patients, RCC was diagnosed after the MM at 3, 8, 23 and 46 months, respectively; in the remaining four, the RCC was diagnosed before MM by 108, 35, 13 and 1 months, respectively. The number of cases of RCC expected in the present 1100 patients with MM over 15 years was lower than the four recorded (P < 0.001, Fisher's exact test). Similarly, the number of cases of MM expected in the 2704 patients with RCC was also lower than the four recorded (P < 0.001, Fisher's exact test).

Conclusions: RCC and MM can occur in the same patient at an incidence higher than the expected rate. Possible explanations include genetic abnormalities, environmental exposures or immune-related mechanisms predisposing to the second malignancy. These findings are particularly relevant in the management of patients with known RCC and lytic bone lesions, or those with known MM and subsequent or concomitant renal masses, especially those involving the right kidney.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1464-410X.2007.07268.xDOI Listing
March 2008

Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy.

Cancer 2007 Aug;110(3):543-50

Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio, USA.

Background: Therapy targeted against the vascular endothelial growth factor (VEGF) pathway is a standard of care for patients with metastatic renal cell carcinoma (RCC). The identification of patients who are more likely to benefit from these agents is warranted.

Methods: In total, 120 patients with metastatic clear-cell RCC received bevacizumab, sorafenib, sunitinib, or axitinib on 1 of 9 prospective clinical trials at the Cleveland Clinic. Clinical features associated with outcome were identified by univariate analysis; then, a stepwise modeling approach based on Cox proportional hazards regression was used to identify independent prognostic factors and to form a model for progression-free survival (PFS). A bootstrap algorithm was used to provide internal validation.

Results: The overall median PFS was 13.8 months, and the objective response according to the Response Criteria in Solid Tumors was 34%. Multivariate analysis identified time from diagnosis to current treatment <2 years; baseline platelet and neutrophil counts >300 K/microL and >4.5 K/microL, respectively; baseline corrected serum calcium <8.5 mg/dL or >10 mg/dL; and initial Eastern Cooperative Oncology Group performance status >0 as independent, adverse prognostic factors (PF) for PFS. Three prognostic subgroups were formed based on the number of adverse prognostic factors present. The median PFS in patients with 0 or 1 adverse prognostic factor was 20.1 months compared with 13 months in patients with 2 adverse prognostic factors and 3.9 months in patients with >2 adverse prognostic factors.

Conclusions: Five independent prognostic factors for predicting PFS were identified and were used to categorize patients with metastatic RCC who received VEGF-targeted therapies into 3 risk groups. These prognostic factors can be incorporated into patient care and clinical trials that use such novel, VEGF-targeted agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.22827DOI Listing
August 2007

Phase II study of lenalidomide in patients with metastatic renal cell carcinoma.

Cancer 2006 Dec;107(11):2609-16

Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio, USA.

Background: Lenalidomide (LEN) is a structural and functional analogue of thalidomide that has demonstrated enhanced immunomodulatory properties and a more favorable toxicity profile. A Phase II, open-label study of LEN in patients with metastatic renal cell carcinoma (RCC) was conducted to determine its safety and clinical activity.

Methods: Patients with metastatic RCC received LEN orally at a dose of 25 mg daily for the first 21 days of a 28-day cycle. The primary endpoint was the objective response rate. Time to treatment failure, safety, and survival were secondary endpoints.

Results: In total, 28 patients participated in the trial and were included in the current analysis. Three of 28 patients (11%) demonstrated partial responses and continued to be progression-free for >15 months. Eleven patients (39%) had stable disease that lasted >3 months, including 8 patients who had tumor shrinkage. In total, 6 patients (21%) remained on the trial, and 5 additional patients continued to be followed for survival. The median follow-up for those 11 patients was 13.5 months (range, 8.3-17.0 months). The median survival had not been reached at the time of the current report. Serious adverse events included fatigue (11%), skin toxicity (11%), and neutropenia (36%).

Conclusions: LEN demonstrated an antitumor effect in metastatic RCC, as evidenced by durable partial responses. LEN toxicities were manageable. Further studies will be required to assess the overall activity of LEN in patients with metastatic RCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.22290DOI Listing
December 2006
-->