Publications by authors named "Glenn M Mills"

34 Publications

Plasmablastic Lymphoma, a Rare Entity in Bone Marrow with Unusual Immunophenotype and Challenging Differential Diagnosis.

Case Rep Hematol 2019 2;2019:1586328. Epub 2019 Sep 2.

Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.

Plasmablastic lymphoma (PBL) is an aggressive malignancy that usually occurs in the setting of immunosuppression. The immunohistochemical profile of PBL is that of terminally differentiated B lymphocytes. CD138, CD38, and MUM1 are usually immunopositive. However, pan B-cell markers such as CD20 and PAX-5 are usually negative. rearrangement is the most commonly encountered genetic alteration, with immunoglobulin (), especially immunoglobulin heavy () chain, being the most frequent partner. We report a case of PBL in a 48-year-old human immunodeficiency virus- (HIV-) positive male who was admitted to the hospital with signs and symptoms suspicious for tumor lysis syndrome. Bone marrow examination revealed hypercellular marrow with trilineage hypoplasia and sheets of intermediate to large neoplastic cells with basophilic vacuolated cytoplasm comprising the majority of cellular elements of the bone marrow. The neoplastic cells were negative for conventional B-cell, T-cell, plasma cell, and myeloid markers, while flow cytometric analysis revealed an abnormal CD45-dim population that was partially weakly positive for CD71 and CD79b. The diagnosis was initially thought to be a high-grade primitive hematopoietic neoplasm, possibly an acute undifferentiated leukemia. BOB-1, however, was immunopositive in the neoplastic cells, confirming its B-cell origin. MYC was positive by immunohistochemistry and break-apart FISH, as were CD45, MUM-1, and EMA immunostains. There was immunoglobulin kappa () light chain gene rearrangement by polymerase chain reaction (PCR). Additionally, Epstein-Barr virus- (EBV-) encoded small RNAs (EBER) were positive by in situ hybridization (ISH). The tumor proliferation index by Ki-67 immunostaining approached 95%. Although the tumor cells were negative for CD38 and CD138, the diagnosis of PBL was still rendered. We recommend using a broad spectrum of B-cell markers, including BOB-1 and OCT-2, in such challenging cases of B-cell lymphomas with no expression of conventional B-cell markers. We also emphasize that the negative CD38 and CD138 should not exclude PBL from the differential diagnosis.
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http://dx.doi.org/10.1155/2019/1586328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745100PMC
September 2019

Autologous transplantation as consolidation for high risk aggressive T-cell non-Hodgkin lymphoma: a SWOG 9704 intergroup trial subgroup analysis.

Leuk Lymphoma 2019 08 10;60(8):1934-1941. Epub 2019 Jan 10.

a Cardinal Bernardin Cancer Center, Loyola University Medical Center , Maywood , IL , USA.

Phase II data suggest a benefit to autotransplantation for aggressive T-cell non-Hodgkin lymphoma (T-NHL) in first remission; randomized trials have yet to validate this. We performed a retrospective analysis of aggressive T-NHL patients in the intergroup randomized consolidative autotransplant trial (SWOG 9704). Of the 370 enrolled, 40 had T-NHL: 12 were not randomized due to ineligibility ( = 1), choice ( = 2), or progression ( = 9), leaving 13 randomized to control and 15 to autologous stem cell transplantation (ASCT). Two ASCT patients refused transplant and one failed mobilization. The 5-year landmark PFS/OS estimates for ASCT vs. control groups were 40% vs. 38% ( = .56), and 40% vs. 45% ( = .98), respectively. No difference was seen based on IPI, or histologic subtype. Only 1/7 receiving BCNU-based therapy survived vs. 4/5 receiving TBI. Aggressive T-NHL autotransplanted in first remission did not appear to benefit from consolidative ASCT. This and the 30% who dropped out pre-randomization mostly to progression, suggests that improved induction regimens be developed.
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http://dx.doi.org/10.1080/10428194.2018.1563691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620162PMC
August 2019

Use of Eltrombopag in Improving Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation.

Case Rep Oncol 2018 Jan-Apr;11(1):191-195. Epub 2018 Mar 27.

Division of Hematology and Oncology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.

Eltrombopag is a thrombopoietin agonist and has been used in aplastic anemia and post-transplantation thrombocytopenia. The c-MPL receptor is present on hematopoietic stem cells. There are no reports of eltrombopag utilization for improving poor graft function in the post-transplant setting. Here were report a case of a young female with post-transplant poor graft function as evident from the low absolute neutrophil count, anemia, and thrombocytopenia on day 60. Eltrombopag was started on day 72 and resulted in improvement in all 3 cell lines. The counts continued to be stable even after eltrombopag was discontinued. The patient tolerated the drug without significant side effects for 1 year.
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http://dx.doi.org/10.1159/000487229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903126PMC
March 2018

Successful Treatment of Richter Transformation with Ibrutinib in a Patient with Chronic Lymphocytic Leukemia following Allogeneic Hematopoietic Stem Cell Transplant.

Case Rep Oncol 2017 May-Aug;10(2):534-541. Epub 2017 Jun 19.

Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.

Patients with chronic lymphocytic leukemia (CLL) who progress to Richter transformation (RT) have a poor prognosis. Multi-agent chemotherapy regimens do not have good response rates. There are few case reports on the use of ibrutinib in RT. Here, we present a patient who was heavily pretreated for CLL, including allogeneic stem cell transplant, and progressed to RT. She had a mixed response to multi-agent chemotherapy and was started on ibrutinib. She had a complete response for 16 months on single-agent ibrutinib with minimal toxicity.
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http://dx.doi.org/10.1159/000477338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498945PMC
June 2017

Immune checkpoint inhibitors: the new frontier in non-small-cell lung cancer treatment.

Onco Targets Ther 2016 16;9:5101-16. Epub 2016 Aug 16.

Department of Medicine, Division of Hematology-Oncology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.

Lung cancer is the major cause for cancer-related death in the US. Although advances in chemotherapy and targeted therapy have improved the outcome of metastatic non-small-cell lung cancer, its prognosis remains dismal. A deeper understanding of the complex interaction between the immune system and tumor microenvironment has identified immune checkpoint inhibitors as new avenue of immunotherapy. Rather than acting directly on the tumor, these therapies work by removing the inhibition exerted by tumor cell or other immune cells on the immune system, promoting antitumoral immune response. To date, two programmed death-1 inhibitors, namely nivolumab and pembrolizumab, have received the US Food and Drug Administration approval for the treatment of advanced non-small-cell lung cancer that failed platinum-based chemotherapy. This manuscript provides a brief overview of the pathophysiology of cancer immune evasion, summarizes pertinent data on completed and ongoing clinical trials involving checkpoint inhibitors, discusses the different strategies to optimize their function, and outlines various challenges that are faced in this promising yet evolving field.
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http://dx.doi.org/10.2147/OTT.S111209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993420PMC
August 2016

Effect of Payer Status on Relative Survival of Patients with Laryngeal Cancer.

Anticancer Res 2016 Jan;36(1):327-33

Department of Medicine & Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA, U.S.A.

Background: Relative survival (RS) for patients with laryngeal cancer in the US population has yet to be described. Additionally, survival of patients with laryngeal cancer has demonstrated socioeconomic and racial disparities which have not been previously examined through the lens of RS.

Materials And Methods: Data on 58,814 patients with laryngeal cancer were obtained from the National Cancer Database. Patients were diagnosed between 1998 and 2006, and had at least 5 years of follow-up. Birth-, year-, age-, sex- and race-specific matched life expectancies were used to estimate expected survival. Stage-stratified RS rates were calculated with multiple factors assessed for significance. Excess mortality ratios were estimated in multivariate analysis utilizing Poisson regression.

Results: Younger age, African-American race, uninsured or Medicaid insurance, and treatment at an academic center were all significantly associated with stage IV disease. Uninsured and Medicaid patients demonstrated decreased RS when compared to privately insured individuals. Excess mortality was markedly pronounced in the first year for patients over 50 years old with stage II-IV disease, especially for the over 75-year-old cohort.

Conclusion: Survival disparities for uninsured and Medicaid populations were found, with these patients exhibiting increased excess mortality. Additionally, RS calculations highlight the negative effects of increasing age on survival of patients with laryngeal cancer.
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January 2016

The Shreveport Myeloma Experience: Survival, Risk Factors and Other Malignancies in the Age of Stem Cell Transplantation.

Acta Haematol 2016 21;135(3):146-55. Epub 2015 Nov 21.

Feist Weiller Cancer Center, Shreveport, La., USA.

Background: The overall prognosis of multiple myeloma has improved significantly over the last 15 years. We wondered whether the overall improvement would also be seen in unselected patients in an academic center in Northwest Louisiana with a high proportion of minority patients, and if second malignant neoplasms are relevant for our patients.

Materials And Methods: Between 1998 and 2009, 215 patients were treated for multiple myeloma at our center and had complete follow-up until May 2013.

Results: The mean survival of patients with multiple myeloma increased from 3.25 to 5.34 years, which is comparable to patients treated at larger centers. No prognostic difference was observed in the subgroups of myeloma patients. Among 215 patients followed for the development of secondary cancers, 16 already had a preexisting or concomitant malignancy (7.4%) and 10 developed secondary cancers. Our data indicate a significant background of histologically unrelated cancers and a cumulative incidence of new cancers of about 20% after 10 years of follow-up. Based on SEER data, preexisting or secondary cancers were not statistically increased in our population.

Conclusions: The use of autologous transplantation and the introduction of new agents resulted in a significant improvement in the prognosis of multiple myeloma. Other cancers are not statistically increased before or after multiple myeloma is diagnosed and are not prognostically relevant.
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http://dx.doi.org/10.1159/000440970DOI Listing
June 2016

Effect of ArginMax on sexual functioning and quality of life among female cancer survivors: results of the WFU CCOP Research Base Protocol 97106.

J Community Support Oncol 2015 Mar;13(3):87-94

Comprehensive Cancer Center of Wake Forest University CCOP Research Base, Winston-Salem, North Carolina, USA.

Background: Problems with sexual functioning are common following therapy for breast and gynecologic cancers, although there are few effective treatments.

Objective: To assess the impact of ArginMax, a nutritional supplement comprised of extracts of L-arginine, ginseng, gingko, and damiana, as well as multivitamins and minerals, on sexual functioning and quality of life in female cancer survivors.

Methods: This was a 12-week, randomized, placebo-controlled trial of eligible patients who were 6 months or more from active treatment and reporting problems with sexual interest, satisfaction, and functioning after therapy. The participants took 3 capsules of Arginmax or placebo twice daily. Outcome measures were the Female Sexual Function Inventory (FSFI) and the Functional Assessment of Cancer Therapy - General (FACT-G). Assessments were done at baseline, 4, 8, and 12 weeks.

Results: 186 patients with a median age of 50 years were accrued between May 10, 2007 and March 24, 2010. 76% of the patients were non-Hispanic white. Most had breast or a gynecologic cancer (78% and 12%, respectively). At 12 weeks, there were no differences between the ArginMax group (n = 96) and placebo (n = 92) group in sexual desire, arousal, lubrication, orgasm,satisfaction or pain. However, FACT-G total scores were significantly better for participants who took ArginMax compared with those who took placebo (least squares [LS] means, 87.5 vs 82.9, respectively; P = .009). The Fact-G subscales that were most affected were Physical (25.37 vs. 23.51, P = .001) and Functional Well-Being (22.46 vs. 20.72, P = .007). Toxicities were similar for both groups.

Limitations: Study results are limited by a lack of data on the participants' psychological and physical symptoms and sexual partner variables.

Conclusions: ArginMax had no significant impact on sexual functioning, but patient quality of life was significantly better at 12 weeks in participants who received ArginMax.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544777PMC
http://dx.doi.org/10.12788/jcso.0114DOI Listing
March 2015

Tolosa-hunt syndrome in double-hit lymphoma.

Case Rep Oncol Med 2015 30;2015:249891. Epub 2015 Mar 30.

Department of Medicine, Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY 10065, USA.

Tolosa-Hunt syndrome (THS) is a painful condition characterized by hemicranial pain, retroorbital pain, loss of vision, oculomotor nerve paralysis, and sensory loss in distribution of ophthalmic and maxillary division of trigeminal nerve. Lymphomas rarely involve cavernous sinus and simulate Tolosa-Hunt syndrome. Here we present a first case of double-hit B cell lymphoma (DHL) relapsing and masquerading as Tolosa-Hunt syndrome. The neurological findings were explained by a lymphomatous infiltration of the right Gasserian ganglion which preceded systemic relapse. As part of this report, the diagnostic criteria for Tolosa-Hunt syndrome and double-hit lymphoma are reviewed and updated treatment recommendations are presented.
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http://dx.doi.org/10.1155/2015/249891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396905PMC
April 2015

Development and validation of a clinical score for predicting risk of adenoma at screening colonoscopy.

Cancer Epidemiol Biomarkers Prev 2015 Jun 23;24(6):913-20. Epub 2015 Mar 23.

Department of Gastroenterology and Nutrition Service, Memorial Sloan-Kettering Cancer Center, New York, New York.

Background: Currently, no clinical tools use demographic and risk factor information to predict the risk of finding an adenoma in individuals undergoing colon cancer screening. Such a tool would be valuable for identifying those who would most benefit from screening colonoscopy.

Methods: We used baseline data from men and women who underwent screening colonoscopy from the randomized, multicenter National Colonoscopy Study (NCS) to develop and validate an adenoma risk model. The study, conducted at three sites in the United States (Minneapolis, MN; Seattle, WA; and Shreveport, LA) asked all participants to complete baseline questionnaires on clinical risk factors and family history. Model parameters estimated from logistic regression yielded an area under the receiver operating characteristic curve (AUROCC) used to assess prediction.

Results: Five hundred forty-one subjects were included in the development model, and 1,334 in the validation of the risk score. Variables in the prediction of adenoma risk for colonoscopy screening were age (likelihood ratio test for overall contribution to model, P < 0.001), male sex (P < 0.001), body mass index (P < 0.001), family history of at least one first-degree relative with colorectal cancer (P = 0.036), and smoking history (P < 0.001). The adjusted AUROCC of 0.67 [95% confidence interval (CI), 0.61-0.74] for the derivation cohort was not statistically significantly different from that in the validation cohort. The adjusted AUROCC for the entire cohort was 0.64 (95% CI, 0.60-0.67).

Conclusion: We developed and validated a simple well-calibrated risk score.

Impact: This tool may be useful for estimating risk of adenomas in screening eligible men and women.
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http://dx.doi.org/10.1158/1055-9965.EPI-14-1321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452431PMC
June 2015

Cisplatin, cetuximab, and radiation in locally advanced head and neck squamous cell cancer: a retrospective review.

Clin Med Insights Oncol 2015 4;9:1-7. Epub 2015 Jan 4.

Department of Internal Medicine, Division of Oncology, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Efficacy of cisplatin versus cetuximab with radiation in locally advanced head and neck cancer (LAHNC) was evaluated. A total of 96 patients with newly diagnosed LAHNC treated at our institution between 2006 and 2011 with concurrent radiation and cisplatin (group A, n = 45), cetuximab (group B, n = 24), or started with cisplatin but switched to cetuximab because of toxicity (group C, n = 27) were reviewed. Chi-square test, analysis of variance, and log-rank test were used for analysis. The three groups had similar baseline characteristics, except for median age, T stage, albumin levels, hemoglobin levels, performance status, and comorbidities. A complete response (CR) was seen in 77%, 17%, and 67% of patients (P < 0.001), respectively. There was no significant difference in median overall survival (OS) between groups A and C. The median OS for groups A and C was not reached (>65 months), even though it was significantly longer than median OS for group B (11.6 months; P ≤ 0.001). The 2-year OS in groups A and C is significantly higher than that in group B (70% for groups A and C, 22% for group B). There is no significant difference in progression-free survival (PFS) between groups A and C. The median PFS for these groups was not reached (>62 months), and is significantly longer than that for group B (4.3 months; P ≤ 0.001). The 2-year PFS of group A (67%) and group C (76%) was significantly longer than that of group B (20%). Cisplatin with radiation appears to be more efficacious even in suboptimal dosing than cetuximab with radiation in LAHNC but the two groups were not well matched.
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http://dx.doi.org/10.4137/CMO.S18682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283547PMC
January 2015

Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma.

N Engl J Med 2013 Oct;369(18):1681-90

From Loyola University Medical Center, Maywood, IL (P.J.S., K.P.B.); Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle (J.M.U., M.L.); Cleveland Clinic, Cleveland (J.R.C., R.R.T.); University of Rochester, Rochester, NY (L.S.C., J.W.F., R.I.F.); Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, NS (S.C.), University of Calgary-Tom Baker Cancer Centre, Calgary, AB (D.A.S.), and Margaret and Charles Juravinski Cancer Centre, Hamilton, ON (D.M.) - all in Canada; University of North Carolina at Chapel Hill, Chapel Hill (T.C.S.); Ohio State University Medical Center, Columbus (P.P.); Northwestern University, Chicago (J.N.W.); University of Wisconsin, Madison (B.S.K.); University of Arizona, Tucson (T.P.M., L.M.R.); Louisiana State University Health Sciences Center, Shreveport (G.M.M.); City of Hope Medical Center, Duarte, CA (S.J.F.); and Fox Chase Cancer Center-Temple Health, Temple University School of Medicine, Philadelphia (R.I.F.).

Background: The efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse, aggressive non-Hodgkin's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era.

Methods: We treated 397 patients who had disease with an age-adjusted classification of high risk or high-intermediate risk with five cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus rituximab. Patients with a response were randomly assigned to receive three additional cycles of induction chemotherapy (control group) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation (transplantation group). The primary efficacy end points were 2-year progression-free survival and overall survival.

Results: Of 370 induction-eligible patients, 253 were randomly assigned to the transplantation group (125) or the control group (128). Forty-six patients in the transplantation group and 68 in the control group had disease progression or died, with 2-year progression-free survival rates of 69 and 55%, respectively (hazard ratio in the control group vs. the transplantation group, 1.72; 95% confidence interval [CI], 1.18 to 2.51; P=0.005). Thirty-seven patients in the transplantation group and 47 in the control group died, with 2-year overall survival rates of 74 and 71%, respectively (hazard ratio, 1.26; 95% CI, 0.82 to 1.94; P=0.30). Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (P=0.04 for interaction) and overall survival (P=0.01 for interaction). Among high-risk patients, the 2-year overall survival rate was 82% in the transplantation group and 64% in the control group.

Conclusions: Early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy. Overall survival after transplantation was not improved, probably because of the effectiveness of salvage transplantation. (Funded by the National Cancer Institute, Department of Health and Human Services, and others; SWOG-9704 ClinicalTrials.gov number, NCT00004031.).
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http://dx.doi.org/10.1056/NEJMoa1301077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418PMC
October 2013

Superwarfarin intoxication: two case reports and review of pathophysiology and patient management.

J La State Med Soc 2012 Mar-Apr;164(2):70-2

Louisiana State University Health Sciences Center, Shreveport School of Medicine, USA.

Superwarfarin vitamin K antagonists are found in rat poisons and are readily available. Pediatric exposures are common but are usually asymptomatic without significant coagulopathy. Superwarfarin intoxication must be considered in any adult who presents with an unexplained coagulopathy with extreme elevation of prothrombin time and partial thromboplastin time with associated depletion of vitamin K dependent factors. If superwarfarin toxicity is confirmed, intentional ingestion should be considered, as a large quantity of ingested rat poison is necessary to induce a coagulopathy. Patients with superwarfin induced coagulopathy require several months of high dose oral and parenteral vitamin K supplementation. We describe two patients with superwarfarin toxicity treated at Louisiana State University Health in Shreveport and review pathophysiology and patient management.
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August 2012

Colorectal Chemoprevention Pilot Study (SWOG-9041), randomized and placebo controlled: the importance of multiple luminal lesions.

Clin Colorectal Cancer 2011 Dec 22;10(4):310-6. Epub 2011 Jul 22.

City of Hope Medical Center, Duarte, CA, USA.

Background: Colorectal cancer is common worldwide and chemoprevention has the potential of reducing the number of individuals who may suffer and perish from this disease.

Methods: A randomized placebo controlled pilot study in colorectal cancer patients was performed using calcium carbonate as the test agent in a multi-institutional oncology study group.

Results: Two hundred twenty volunteers were randomized in the study. The primary goals of compliance, accrual, and toxicity monitoring are presented. Presence of multiple adenomas at study entry and subsequent development of metachronous adenomas were recorded and found to be associated with synchronous adenomas. The secondary endpoint of recurrent adenomas indicated lower rates of new adenoma in the volunteers randomized to the calcium group.

Conclusion: This pilot study indicates the feasibility of enrolling survivors of colorectal cancer as study volunteers in a colorectal neoplasm chemoprevention clinical trial and oral calcium continues to be a potentially effective drug in reducing colorectal adenomas.
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http://dx.doi.org/10.1016/j.clcc.2011.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286321PMC
December 2011

Phase II evaluation of early oral estramustine, oral etoposide, and intravenous paclitaxel combined with hormonal therapy in patients with high-risk metastatic prostate adenocarcinoma: Southwest Oncology Group S0032.

Urology 2011 May 21;77(5):1172-6. Epub 2011 Feb 21.

University of Michigan, Ann Arbor, Michigan 48109-5948, USA.

Objectives: To assess the efficacy of a multiagent taxane-based chemotherapy combined with hormonal therapy in men with metastatic androgen-dependent prostate cancer in a multicenter, cooperative group, single-arm trial.

Methods: A total of 41 patients with newly diagnosed metastatic prostate cancer involving both the axial and the appendicular skeletons or viscera were enrolled. Of the 41 patients, 35 were treated with combined androgen blockade and ≤4 cycles of oral estramustine (280 mg orally 3 times daily) and etoposide (50 mg/m(2) daily) for 14 days of each 21-day cycle, with paclitaxel (135 mg/m(2) intravenously within 1 hour) on day 2 of each cycle. Chemotherapy was started within 30 days of the initiation of hormonal therapy. The patients were followed up to determine the progression-free survival.

Results: The 35 patients received a total of 126 cycles of chemotherapy, with 30 receiving all 4 cycles. The median progression-free survival for the evaluable population was 13 months (95% confidence interval 10-16), with a median overall survival of 38 months (95% confidence interval 28-49). The main toxicities were myelosuppression, with 9 patients experiencing grade 3 or greater neutropenia and 1 developing grade 4 thrombocytopenia. One patient died of neutropenic infection. Thrombosis embolism occurred 4 times (3 of grade 4 and 1 of grade 3), with 1 episode of grade 4 cardiac ischemia.

Conclusions: The results of our study have shown that the administration of chemotherapy to this population is feasible, with moderate toxicity. Taxane-based chemotherapy did not demonstrate significant efficacy in this high-risk population of patients with a poor prognosis.
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http://dx.doi.org/10.1016/j.urology.2010.12.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528346PMC
May 2011

Metastatic malignant melanoma in a patient with Hodgkin's lymphoma in remission.

J La State Med Soc 2010 Jan-Feb;162(1):47-50

Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.

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June 2010

Pharmacodynamic evaluation of temsirolimus in patients with newly diagnosed advanced-stage head and neck squamous cell carcinoma.

Head Neck 2010 Dec;32(12):1619-28

Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, LA, USA.

Background: Activation of the mammalian target of rapamycin (mTOR) pathway in surgical margins of head and neck squamous cell carcinoma (HNSCC) is a predictor of recurrence and patients with minimal residual disease may benefit from adjuvant therapy with temsirolimus, an mTOR inhibitor.

Methods: The effects of 3 weekly doses of 25 mg of temsirolimus on Akt/mTOR pathway biomarkers were evaluated in tumor and peripheral blood mononuclear cells (PBMCs) of patients with HNSCC. Adverse events were assessed.

Results: Temsirolimus significantly decreased pS6 and p4E-BP1 in tumors, and pS6 and pAkt in PBMCs (p < .05). There was no significant upregulation of pAkt(Ser(473)) in tumor tissue. Side effects were minimal and reversible.

Conclusion: Significant inhibition of the mTOR pathway was noted in both tumors and PBMCs of HNSCC with minimal side effects. The mTOR inhibitors can potentially be used as adjuvant therapy for patients with minimal residual disease and PBMCs are potential surrogate markers in this setting.
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http://dx.doi.org/10.1002/hed.21374DOI Listing
December 2010

Phase 1-2a multicenter dose-ranging study of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy for patients with advanced non-small cell lung cancer.

J Thorac Oncol 2009 Nov;4(11):1389-96

Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA.

Introduction: We aimed to evaluate the safety and efficacy of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer.

Methods: This was a phase 1-2a, multicenter, dose-ranging trial that enrolled patients with stage IIIB or IV non-small cell lung cancer with measurable disease. Patients received canfosfamide in doses ranging from 400 to 1000 mg/m2 intravenously (IV) with carboplatin at area under the curve 6 IV and paclitaxel at 200 mg/m2 IV day 1 every 3 weeks. The primary end point was objective response rate, and the secondary endpoints were safety and progression-free survival.

Results: One hundred twenty-nine patients were treated with canfosfamide at dose levels of 400 (n = 3), 500 (n = 51), 750 (n = 54), and 1000 mg/m2 (n = 21). Objective tumor responses by RECIST were observed in 40 patients [34% (95% confidence interval [CI], 26-44)], the median progression-free survival was 4.3 months (95% CI, 3.7-5.2) and the median survival 9.9 months (95% CI, 7.7-11.9). The percent of patients alive at 1 year was 43.1%. The overall safety profile of the combination was acceptable and consistent with the profiles of the individual agents. In an exploratory analysis, patients receiving the optional maintenance canfosfamide therapy had a prolonged median survival of 16.8 months compared with those eligible for but not receiving maintenance therapy at 8.8 months (hazard ratio = 0.38, p < 0.001).

Conclusions: The combination of canfosfamide with carboplatin and paclitaxel chemotherapy is well tolerated and active. Maintenance canfosfamide may further improve outcomes. This regimen is worthy of additional study.
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http://dx.doi.org/10.1097/JTO.0b013e3181b6b84bDOI Listing
November 2009

Docetaxel, cisplatin, and fluorouracil induction chemotherapy followed by accelerated fractionation/concomitant boost radiation and concurrent cisplatin in patients with advanced squamous cell head and neck cancer: A Southwest Oncology Group phase II trial (S0216).

Head Neck 2010 Feb;32(2):221-8

Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA.

Background: In an effort to optimize nonoperative therapy in patients with locoregionally advanced head and neck squamous cell cancer, the Southwest Oncology Group conducted a phase II trial combining 3-drug taxane-containing induction chemotherapy with accelerated fractionation/concomitant boost radiation and concomitant single-agent cisplatin.

Methods: Two induction courses using docetaxel (75 mg/m(2) on day 1), cisplatin (100 mg/m(2) on day 1), and fluorouracil (1000 mg/m(2)/day continuous intravenous infusion days 1-4) were given, with an interval of 21 days. Patients who were stable or responded to the chemotherapy received definitive accelerated fractionation/concomitant boost radiation with concurrent cisplatin (100 mg/m(2)) on days 1 and 22 of radiation.

Results: There were 74 eligible and evaluable patients enrolled between March 1, 2003, and August 15, 2004; 52 (70%) had stage IV disease. At least 1 grade 3-4 toxicity was experienced by 63 patients (85%) during induction. A total of 61 patients completed induction and began concurrent chemoradiotherapy; 50 (68%) completed all planned treatment. At least 1 grade 3-4 toxicity was noted in 53 of the 58 patients (91%) evaluated for toxicity from concurrent chemoradiotherapy. Two patients died during induction, and 2 during chemoradiation. With a median follow-up of 36 months (range, 14-50), the 2-year and 3-year overall survival estimates were 70% and 64%, with 2-year and 3-year progression-free survival estimates of 66% and 61%, respectively.

Conclusions: Three-drug induction chemotherapy followed by accelerated fractionation/concomitant boost radiation and concurrent cisplatin is toxic but feasible within a cooperative group. In this patient cohort with advanced head and neck squamous cell cancer, overall and progression-free survivals were encouraging, justifying further study of this approach.
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http://dx.doi.org/10.1002/hed.21179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967367PMC
February 2010

Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426).

Cancer 2008 Jun;112(11):2393-400

Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Background: Antiandrogen withdrawal is a potential therapeutic maneuver for patients with progressive prostate cancer. This study was designed to examine antiandrogen withdrawal effects within the context of a large multi-institutional prospective trial.

Methods: Eligibility criteria included progressive prostate adenocarcinoma despite combined androgen blockade. Eligible patients received prior initial treatment with an antiandrogen plus orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist. Patients were stratified according to type of antiandrogen, type of progression (prostate-specific antigen [PSA] or radiographic), presence or absence of metastatic disease, and prior LHRH agonist versus surgical castration.

Results: A total of 210 eligible and evaluable patients had a median follow-up of 5.0 years; 64% of patients previously received flutamide, 32% bicalutamide, and 3% nilutamide. Of the 210 patients, 21% of patients had confirmed PSA decreases of >or=50% (95% CI, 16% to 27%). No radiographic responses were recorded. Median progression-free survival (PFS) was 3 months (95% CI, 2 months to 4 months); however, 19% had 12-month or greater progression-free intervals. Median overall survival (OS) after antiandrogen withdrawal was 22 months (20 and 40 months for those with and without radiographic evidence of metastatic disease, respectively). Multivariate analyses indicated that longer duration of antiandrogen use, lower PSA at baseline, and PSA-only progression at study entry were associated with both longer PFS and OS. Longer antiandrogen use was the only significant predictor of PSA response.

Conclusions: These data indicate a relatively modest rate of PSA response in patients who were undergoing antiandrogen withdrawal; however, PFS can be relatively prolonged (>or=1 year) in approximately 19% of patients.
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http://dx.doi.org/10.1002/cncr.23473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359896PMC
June 2008

Phase II study of gemcitabine and cisplatin in patients with previously untreated extensive stage small cell lung cancer: Southwest Oncology Group Study 9718.

J Thorac Oncol 2007 May;2(5):440-4

Caritas St. Elizabeth's Medical Center of Boston, Boston, Massachusetts 02135, USA.

Background: This phase II study (S9718) evaluated the antineoplastic activity and tolerability of the combination of gemcitabine and cisplatin in previously untreated patients with extensive stage small cell lung cancer (ES-SCLC).

Methods: Chemonaive patients with ES-SCLC, received gemcitabine 1250 mg/m intravenously (IV) over 30 minutes on days 1 and 8 and cisplatin 75 mg/m IV over 30 to 60 minutes on day 1. Treatments were repeated every 21 days for a maximum of six cycles.

Results: A total of 88 patients were enrolled in the study; seven patients were not eligible and one did not receive treatment; 80 patients were fully assessable for survival, response, and toxicity. Objective response was observed in 42 patients (53%; 95% confidence interval [CI]: 41%-64%) with two patients (3%; 95% CI: 0%-8%) achieving a complete response. Median PFS was 5 months (CI, 4.2-5.9 months), and median overall survival was 8.8 months (95% CI: 7.8-9.5 months). The 1- and 2-year survival rates were 27.5% (95% CI: 17.7%-37.3%) and 4% (95% CI: 0%-8%), respectively. The most common toxicity was neutropenia. Grade 3 and 4 neutropenia was noted in 17 (21%) and 17 (21%) patients, respectively. Two patients developed febrile neutropenia, with subsequent full recovery. Twenty-one patients (23%) developed grade 3 thrombocytopenia. Grade 4 thrombocytopenia was seen in only one patient. The most common nonhematologic toxicities included grade 3 and 4 vomiting in 12 (21%) patients and fatigue in nine (10%) patients. Two patients (3%) died of respiratory infections while on treatment.

Conclusion: The combination of gemcitabine and cisplatin is an active and reasonably well tolerated regimen for the treatment of ES-SCLC. It does not appear to offer any compelling advantages over other commonly used two drug regimens in this disease.
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http://dx.doi.org/10.1097/01.JTO.0000268678.25615.33DOI Listing
May 2007

Treatment of elderly non-small cell lung cancer patients with three different schedules of weekly paclitaxel in combination with carboplatin: subanalysis of a randomized trial.

J Thorac Oncol 2006 Mar;1(3):240-4

University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, USA.

Background: Administration of paclitaxel on a weekly schedule in combination with carboplatin is associated with a lower incidence of neuropathy and myelosuppression. The authors conducted subgroup analysis of their randomized phase II study of three different schedules of weekly paclitaxel with carboplatin to determine the efficacy of each regimen in elderly patients (aged > or = 70 years) with advanced non-small-cell lung cancer (NSCLC).

Methods: Patients with advanced NSCLC were randomized to one of three different weekly paclitaxel/carboplatin regimens. After four cycles of chemotherapy, those with objective response or stable disease were randomized to weekly paclitaxel or observation as maintenance therapy. Four hundred three patients were enrolled in the study, of whom 111 (28%) were aged 70 years or older.

Results: The treatment regimen of weekly paclitaxel (100 mg/m for 3 of 4 weeks) and carboplatin (area under the curve = 6 mg/ml/min once every 4 weeks) (arm 1) was associated with the best therapeutic index overall. The median survival and 1-year survival rates were 11.3 months and 50% for patients in the > or =70 years cohort versus 11.2 months and 46% for the <70 years cohort in arm 1. Efficacy results were comparable between the two groups in the other arms as well. Grade 4 neutropenia and febrile neutropenia occurred in 13.6% and 2.3% in the > or =70 years cohort compared with 4.5% and 1.1% in the <70 years cohort in arm 1.

Conclusion: The weekly regimen of paclitaxel administered in combination with carboplatin is tolerated well by elderly NSCLC patients and has comparable efficacy with younger patients.
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http://dx.doi.org/10.1016/s1556-0864(15)31574-4DOI Listing
March 2006

A gut reaction?

Am J Med 2007 Feb;120(2):143-5

Department of Internal Medicine, Louisiana State University Health Sciences Center, Shreveport, USA.

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http://dx.doi.org/10.1016/j.amjmed.2006.12.008DOI Listing
February 2007

Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003.

J Clin Oncol 2005 Dec;23(36):9097-104

University of Kansas Medical Center, Kansas City, KS, USA.

Purpose: Tumor hypoxia confers chemotherapy resistance. Tirapazamine is a cytotoxin that selectively targets hypoxic cells. We conducted a phase III clinical trial to determine whether the addition of tirapazamine to paclitaxel and carboplatin offered a survival advantage when used in the treatment of patients with advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Of 396 patients registered, 367 eligible patients were randomly assigned to either arm 1 (n = 181), which consisted of treatment every 21 days with paclitaxel 225 mg/m2/3 h, carboplatin (area under the curve = 6), and tirapazamine 260 mg/m2 in cycle 1 (which was escalated, if tolerable, to 330 mg/m(2) in cycle 2), or arm 2 (n = 186), which consisted of paclitaxel and carboplatin as in arm 1 with no tirapazamine.

Results: Patient characteristics were similar between the two arms. There were no statistically significant differences in response rates, progression-free survival, or overall survival. Patients on arm 1 had significantly (P < .05) more abdominal cramps, fatigue, transient hearing loss, febrile neutropenia, hypotension, myalgias, and skin rash and were removed from treatment more often as a result of toxicity than patients in arm 2 (26% v 13%, respectively; P = .003). More than 40% of patients did not have the tirapazamine dose escalated, primarily because of toxicity. The trial was closed early after an interim analysis demonstrated that the projected 37.5% improvement in survival (8 v 11 months median survival) in arm 1 was unachievable (P = .003).

Conclusion: The addition of tirapazamine to paclitaxel and carboplatin does not result in improved survival in advanced NSCLC compared with paclitaxel and carboplatin alone but substantially increases toxicity.
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http://dx.doi.org/10.1200/JCO.2005.01.3771DOI Listing
December 2005

Head and neck cancer with simultaneous lung cancer.

J La State Med Soc 2004 Jul-Aug;156(4):193-5

Division of Therapeutic Radiology, Louisiana State University Health Sciences Center, Shreveport, USA.

The simultaneous occurrence of a primary malignant tumor of the lung or pulmonary metastasis in patients with head and neck cancer is uncommon. In response to the question, "Are efforts toward management of cancer in the head and neck region in a person with simultaneous malignant tumor of the lung an exercise in futility?" we present six cases evaluated at the Louisiana State University Health Sciences Center in Shreveport during a 19-year period. Men with squamous cell cancers at both locations and locally advanced malignant tumors of the lung were predominant in this series of patients. Chemoradiation was applied because of extensive disease at one or both neoplastic sites. Long-term survival was not observed in most patients (including the aggressively treated individuals) whose malignant neoplasms were concurrently managed by non-operative means.
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December 2004

Adenoma recurrences after resection of colorectal carcinoma: results from the Southwest Oncology Group 9041 calcium chemoprevention pilot study.

Ann Surg Oncol 2003 Oct;10(8):870-5

City of Hope National Medical Center, Duarte, California, USA.

Background: Colorectal adenomas are the usual precursors to carcinoma in sporadic and hereditary colorectal cancers (CRC).

Methods: A total of 220 CRC patients (stages 0, I, and II) were randomized prospectively in a double-blind pilot study of calcium chemoprevention by using recurrent colorectal adenomas as a surrogate end point. This trial is still in progress, and we report the preliminary findings on adenoma recurrence rates.

Results: Synchronous adenomas were present in 60% of patients, and cancer confined in a polyp was present in 23% of patients. The overall cumulative adenoma recurrence rate was 31% (19% in the first year, 29% for 2 years, and 35% for 3 years). The recurrence rates were greater for patients with synchronous adenomas: 38% at 3 years (P =.01). Lower stage was associated with higher adenoma recurrence rates (P =.04). Factors including age, sex, site of primary cancer, and whether the cancer was confined to a polyp were not significantly associated with differences in adenoma recurrence rates.

Conclusions: The substantial adenoma recurrence rate in patients resected of CRC justifies colonoscopic surveillance on a periodic basis. Patients with higher rates of adenoma recurrences, such as CRC with synchronous adenomas, are ideal subjects for chemoprevention trials.
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http://dx.doi.org/10.1245/aso.2003.03.037DOI Listing
October 2003

Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: a multicenter, randomized, double-blind, phase III study in North America.

Head Neck 2003 Sep;25(9):717-31

Division of Head and Neck Surgery, UCLA School of Medicine, 10833 LeConte Ave., 62-132 CHS, Los Angeles, California 90024, USA.

Background: The objective was to evaluate the efficacy and safety of a novel intratumoral cisplatin/epinephrine injectable gel (CDDP/epi gel) for local control and palliation of tumor-related symptoms in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Patients And Methods: Eighty-seven patients were randomly assigned to either CDDP/epi or placebo gel in this phase III, double-blind study. Tumors were < or =20 cm(3); most recurrences (88%) were in a previously irradiated field. The most symptomatic or threatening tumor was designated as the target tumor. DOSE: 0.25 mL CDDP/epi gel/cm(3) tumor volume.

Treatments: < or =6 weekly intratumoral injections in an 8-week period.

Primary Outcomes: target tumor response and symptom relief.

Results: During the blinded phase, 34% (21 of 62) of patients achieved an objective response (CR or PR) in the target tumor treated with CDDP/epi gel vs 0% (0 of 24) treated with placebo gel (p <.001). Responses occurred within a median of four treatments (range, 2-6) and were durable (median, 95 days; range, 34-168+ days). More patients treated with CDDP/epi gel achieved palliative benefit than did those treated with placebo gel (37% vs 12%, p =.036). Most frequent side effects were local pain and local cutaneous reactions, which resolved over 3-12 weeks. Renal and hematologic toxicities were rare.

Conclusions: This phase III trial showed that CDDP/epi gel significantly reduces tumor burden, palliates tumor-related symptoms, and is an effective local treatment for recurrent tumors.
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http://dx.doi.org/10.1002/hed.10261DOI Listing
September 2003

Multicenter, randomized trial for stage IIIB or IV non-small-cell lung cancer using weekly paclitaxel and carboplatin followed by maintenance weekly paclitaxel or observation.

J Clin Oncol 2003 Aug;21(15):2933-9

University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.

Purpose: To explore the efficacy and safety of three regimens of weekly paclitaxel plus carboplatin as initial therapy and the feasibility of subsequent maintenance therapy versus observation in patients with advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Four hundred one patients were randomly assigned to one of the following arms: arm 1, paclitaxel 100 mg/m2 weekly for 3 of 4 weeks with carboplatin (area under the curve [AUC] = 6) on day 1; arm 2, paclitaxel 100 mg/m2 and carboplatin (AUC = 2) weekly for 3 of 4 weeks; or arm 3, paclitaxel 150 mg/m2 cycle 1 and 100 mg/m2 cycle 2 and carboplatin (AUC = 2) weekly for 6 of 8 weeks. Patients who responded (n = 130) at week 16 were randomly assigned to either weekly paclitaxel therapy (70 mg/m2, 3 of 4 weeks; n = 65) or observation (n = 65).

Results: For the 390 assessable patients, the objective response rates observed with initial therapy were 32% for arm 1, 24% for arm 2, and 18% for arm 3. The median time to progression and median survival times were 30 and 49 weeks for arm 1, 21 and 31 weeks for arm 2, and 27 and 40 weeks for arm 3, respectively. The 1-year survival rates were 47% for arm 1, 31% for arm 2, and 41% for arm 3.

Conclusion: Arm 1, paclitaxel 100 mg/m2 weekly for 3 of 4 weeks with carboplatin (AUC = 6) administered on day 1, demonstrates the most favorable therapeutic index in patients with advanced NSCLC.
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http://dx.doi.org/10.1200/JCO.2003.02.563DOI Listing
August 2003

Is chemoradiation as effective as surgery with postoperative radiotherapy for locally advanced (operable) head and neck cancer? A retrospective observational study.

Radiat Med 2002 Jul-Aug;20(4):217-9

Objective: To determine whether chemoradiation (CX) is as effective as surgery with postoperative radiotherapy (SX) for operable, locally advanced head and neck cancer (LAHNC).

Methods: A retrospective review of 78 patients with operable stage III or IV cancer of the upper aerodigestive tract who were treated by CX (n = 25) or SX (n = 53) during a 20-year period was undertaken.

Results: Fewer patients relapsed regionally when treated by SX than by CX (p = 0.006). On the other hand, there was no significant difference in local recurrence, distant metastasis, 2-year survival rate, or 5-year survival rate between the two patient groups.

Conclusion: Our results suggesting that CX is not as effective as SX for patients with operable LAHNC calls for a randomized trial comparing CX to SX in such cases.
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January 2003
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