Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
1.
Med Oncol ; 37(10): 95, 2020 Sep 26.
Article in English | MEDLINE | ID: mdl-32979106

ABSTRACT

Taxanes and anthracyclines have been among the best-studied chemotherapy classes in castration-resistant prostate cancer (CRPC). Docetaxel (D) 75 mg/m2 every 3 weeks has been the standard first line chemotherapy for CRPC. Encapsulation of doxorubicin in polyethylene glycol-coated liposomes (PLD) was developed to enhance the safety and efficacy of conventional doxorubicin. We hypothesize that the combination of weekly low dose-D and PLD would result in a high response rate and low toxicity. Eligibility criteria included metastatic progressive CRPC, no prior D or PLD and good organ function. After a short phase I with no dose-limiting toxicity, D 30 mg/m2 was administered on days 1, 8 and 15; and PLD 30 mg/m2 on day 1 only, every 28 days. Thirty-seven patients were enrolled. The PSA response rate was 53%. Twenty-two subjects had measurable disease; one (5%) achieved complete response, five (23%) partial response, and twelve (54%) stable disease. Twenty-seven patients (73%) manifested pain relief. The median time to progression was 3.7 months for all patients and 7.9 months for responders. Median overall survival was 16.3 months. Grade 4 neutropenia without infection and anemia occurred in 1 patient each. Grade 3 treatment-related toxicities included: 15% fatigue; 9% neutropenia, anemia and nausea; 6% dehydration and hand-foot syndrome; and 3% infection, febrile neutropenia, thrombosis, stomatitis, headache, vomiting, weight loss and weakness. In this non-comparative study D-PLD demonstrated a higher activity than previously reported with single agent D with favorable side effect profile. A phase 3 study would be needed to evaluate the true benefit of this combination.ClinicalTrials.gov Identifier: NCT00456989.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Docetaxel/administration & dosage , Doxorubicin/analogs & derivatives , Prostatic Neoplasms, Castration-Resistant/drug therapy , Aged , Aged, 80 and over , Doxorubicin/administration & dosage , Humans , Male , Middle Aged , Polyethylene Glycols/administration & dosage , Treatment Outcome
2.
J Pediatr Hematol Oncol ; 42(5): 350-358, 2020 07.
Article in English | MEDLINE | ID: mdl-32576782

ABSTRACT

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and is also seen in adults. Currently, no plasma-based test for the detection of ALL is available. We have cultured the home of a patient with ALL and isolated a mycovirus containing Aspergillus flavus. This culture was subjected to electron microscopy, purification, and mass spectrometry. Using enzyme-linked immunosorbent assay technique, plasma of patients with ALL and long-term survivors of this disease were tested for antibodies, utilizing supernatant of the culture of this organism. The results were compared with 3 groups of controls, including healthy individuals, patients with sickle cell disease, and solid tumors. Using electron microscopy, the isolated A. flavus contained mycovirus particles. In chemical analysis, this organism did not produce any aflatoxin. Using an enzyme-linked immunosorbent assay technique, the supernatant of the culture of the mycovirus containing A. flavus could differentiate ALL patients from each group of controls (P<0.001). These studies provide a new technique for the detection of ALL and may add information for future research regarding leukemogenesis.


Subject(s)
Aspergillosis/complications , Aspergillus flavus/virology , Fungal Viruses/physiology , Plasma/microbiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Adolescent , Adult , Aspergillosis/microbiology , Aspergillosis/virology , Case-Control Studies , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Prognosis , Young Adult
3.
Indian J Hematol Blood Transfus ; 34(3): 530-534, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30127566

ABSTRACT

Venous thromboembolism (VTE) is a complication of malignancy that is associated with significant mortality. The CLOT trial showed superiority of dalteparin in comparison to warfarin in preventing VTE recurrence. Rivaroxaban has been approved for treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE). In the absence of large randomized trials in the oncology population, the efficacy and safety of rivaroxaban for the treatment of VTE in cancer patients needs to be assessed. A single-center retrospective chart review was conducted to assess the efficacy and safety of rivaroxaban compared with dalteparin in cancer-associated thrombosis. Out of 671 patients identified, 286 patients (107 in the rivaroxaban group and 179 in the dalteparin group) were eligible for analysis. The rivaroxaban group had a rate of VTE recurrence at 6 months of 4.9 versus 11.1% with dalteparin (p = 0.252). The incidence of recurrent DVT at 6 months was lower in patients treated with rivaroxaban (0%) compared with dalteparin (8.2%) at 6 months (p = 0.025). Incidence of recurrent PE in the rivaroxaban group (5%) versus dalteparin group (3.1%) at 6 months was not statistically significant (p = 0.675). No significant difference was identified between the rivaroxaban group and dalteparin group in the rate of major bleeding (2.8 vs. 1.1%, respectively). Rivaroxaban was comparable to dalteparin in prevention of VTE recurrence while having no significant differences with major or minor bleeding.

4.
Cancer ; 123(22): 4411-4418, 2017 11 15.
Article in English | MEDLINE | ID: mdl-28749548

ABSTRACT

BACKGROUND: The impact of MYC proto-oncogene, basic helix-loop-helix (MYC) translocations (with or without additional rearrangements involving the B-cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B-cell lymphoma (DLBCL) who experience primary treatment failure is not well defined. METHODS: This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy. RESULTS: The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC-negative (n = 120), MYC-positive single hit (SH) (n = 20), and MYC-positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2-year overall survival rate was 29.9% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 9.9% in the MYC-positive DH/TH cohort (P < .001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC-positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98-2.96; P = .06) and those with MYC-positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41-3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2-year overall survival rate was 55.4% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 19.4% in the MYC-positive DH/TH cohort (P < .001). All 4 MYC-positive patients who underwent allogeneic HCT relapsed in <4 months. CONCLUSIONS: Patients with MYC-positive DLBCL who experience primary treatment failure have response rates to similar to those achieved by salvage therapy compared with their MYC-negative counterparts, but their survival is dismal irrespective of additional "hits" and HCT, representing an unmet medical need. Cancer 2017;123:4411-8. © 2017 American Cancer Society.


Subject(s)
Genes, myc , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/therapy , Translocation, Genetic , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm/genetics , Female , Hematopoietic Stem Cell Transplantation , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Proto-Oncogene Mas , Recurrence , Retrospective Studies , Salvage Therapy , Treatment Outcome , Young Adult
5.
Leuk Res ; 38(4): 443-6, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24439565

ABSTRACT

For patients with acute myeloid leukemia from antecedent myelodysplastic syndrome particularly after azanucleoside treatment failure, outcome is poor. Here, we conducted a case-control study in these patients to compare the efficacy of CLAG-M induction (28 patients) versus standard 3+7 induction chemotherapy (24 patients). Response rates (P=0.014) and median overall survival (P=0.025) were 64% and 202 days (95% CI 37-367 days) versus 29% and 86 days (95% CI 36-136) in the CLAG-M and 3+7 cohorts, respectively. Median overall survival was 202 (95% CI 37-367 days) versus 86 days (95% CI 36-136) (P=0.025), respectively. CLAG-M has encouraging activity in this patient group.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Azacitidine/therapeutic use , Granulocyte Colony-Stimulating Factor/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Mitoxantrone/administration & dosage , Myelodysplastic Syndromes/drug therapy , Adult , Aged , Aged, 80 and over , Case-Control Studies , Chemotherapy, Adjuvant/adverse effects , Chemotherapy, Adjuvant/standards , Cladribine , Cytarabine , Disease Progression , Drug Resistance, Neoplasm/drug effects , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/adverse effects , Humans , Induction Chemotherapy/adverse effects , Induction Chemotherapy/standards , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Mitoxantrone/adverse effects , Myelodysplastic Syndromes/pathology , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Treatment Failure , Young Adult
6.
Leuk Res ; 37(3): 300-4, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23273539

ABSTRACT

Given evidence for the role of Src family kinases, especially Lyn kinase, in myeloblast proliferation and the in vitro inhibitory activity of dasatinib on Src and Lyn, we conducted a phase II study to assess overall response to 100mg/day dasatinib in patients with higher-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia, or acute myeloid leukemia arising from MDS and who had failed prior treatment with azanucleoside analogs. Among 18 patients treated, 3 responded, 4 had stable disease, and 10 experienced disease progression. Toxicities were limited and consistent with previous reports. Dasatinib appears to be safe but with limited efficacy.


Subject(s)
Myelodysplastic Syndromes/drug therapy , Pyrimidines/administration & dosage , Thiazoles/administration & dosage , Administration, Oral , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Dasatinib , Female , Humans , Male , Middle Aged , Myelodysplastic Syndromes/mortality , Pilot Projects , Pyrimidines/adverse effects , Risk , Salvage Therapy , Severity of Illness Index , Standard of Care , Thiazoles/adverse effects , Treatment Failure
7.
Am J Clin Oncol ; 32(4): 429-31, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19451801

ABSTRACT

PURPOSE: To evaluate the usefulness of routine blood cultures in patients who develop temperatures of 38.5 degrees C or higher while treated with interleukin-2 (IL-2). METHODS: Retrospective chart review study. Charts of patients treated with high-dose IL-2 or biochemotherapy for metastatic melanoma were reviewed at the University of Louisville from 2005 to 2007. The study objective was to estimate the frequency of true and false positive blood cultures. RESULTS: A total of 205 blood cultures in 46 patients (27 male, 19 female) were reviewed. The average age was 53 years (25-71 years). The patients had an average of 3 cycles of therapy. The mean temperature of the febrile episodes was 38.7 degrees C. The mean absolute neutrophil count was 5.1 K/microL. Of these 205 febrile episodes, only 1 blood culture was true positive. The patient had methicillin sensitive staphylococcus aureus bacteremia. There were 5 false positive blood cultures. Four hundred thirty-four further febrile episodes were documented without blood cultures drawn. None of these patients were found to be infected. The yield of true positive blood cultures in this setting was 0.5% (0%-3%, CI). There was, however, a higher number of false positive blood cultures, 2.4% (0.5%-4.5%, CI). CONCLUSIONS: Blood cultures during IL-2 containing therapy are very inefficient to differentiate between infections versus IL-2-related fever.


Subject(s)
Bacteremia/blood , Blood/microbiology , Interleukin-2/adverse effects , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Unnecessary Procedures , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bacteremia/etiology , Cohort Studies , Confidence Intervals , Diagnostic Tests, Routine/statistics & numerical data , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Fever/blood , Fever/etiology , Follow-Up Studies , Humans , Interleukin-2/therapeutic use , Male , Melanoma/blood , Melanoma/pathology , Middle Aged , Neoplasm Staging , Probability , Retrospective Studies , Skin Neoplasms/blood , Skin Neoplasms/pathology
8.
Exp Mol Pathol ; 87(2): 94-8, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19393644

ABSTRACT

GOAL: Human Papillomavirus (HPV) is found to be increasingly implicated in head and neck cancers. The objective of this study was to determine the primary site of origin of HPV positive squamous carcinomas metastatic to lymph nodes of the neck. METHODS: Surgical pathology records from January 1, 2000 to July 31, 2007 were used to identify surgically removed neck lymph nodes with the diagnosis of metastatic squamous carcinoma. Specimens in formalin-fixed, paraffin-embedded blocks were examined for HPV (+) by analyzing sequencing data generated by PCR and immunostaining for the expression of the p16INK biomarker, which is overexpressed if Rb is not present. H & E stained slides were also reviewed for histological classification. The available retrospective demographics were extracted from the charts to determine trends of confounding factors. RESULTS: Of the 43 patient samples, 41 contained adequate DNA to test for HPV. The mean age of the 41 patients was 62 years. All of the patients smoked and 39/41 patients consumed alcohol. The overall HPV (+) incident rate was 27% (11/41) by PCR with strongly diffuse or strong focal p16 staining. 9 of the 34 males and 2 of the 7 females had HPV (+) carcinomas. The average age of the 2 HPV (+) females was 44, compared to the HPV (-) females who averaged 70. The average age of the HPV (+) males was 56 compared with the average age 55 of the HPV (-) males. HPV (+) carcinomas appeared to arise from multiple sites in the oropharynx, particularly the tonsils and tongues, including unknown primaries. By histological exam, most metastatic HPV(+) squamous carcinomas were poorly differentiated (basaloid) microscopically and grossly cystic. CONCLUSION: The 27% HPV (+) squamous cancers metastatic to neck lymph node originated from multiple sites in the oropharynx. The HPV (+) female population, although a total of only 2, tended to be much younger than the HPV (-) ones, whereas the HPV (+) male population was similar in age to the HPV (-) male population.


Subject(s)
Carcinoma, Squamous Cell/virology , Head and Neck Neoplasms/virology , Neoplasms, Unknown Primary/virology , Papillomavirus Infections/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , DNA, Viral/analysis , Female , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , Incidence , Lymphatic Metastasis/pathology , Male , Middle Aged , Neoplasms, Unknown Primary/pathology , Papillomavirus Infections/complications , Polymerase Chain Reaction , Retrospective Studies
SELECTION OF CITATIONS
SEARCH DETAIL
...