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Biomedical subjects

Joseph M Connors

Publications and source records attributed to Joseph M Connors.

At least 37 records · Page 2Linked to original sources
PubMed2005

Primary paranasal sinus lymphoma: natural history and improved outcome with central nervous system chemoprophylaxis.

Non-Hodgkin's lymphoma of the paranasal sinus is an uncommon presentation of extranodal lymphoma. Its natural history, treatment and prognosis have been infrequently characterized in the medical literature; however, a tendency to involve the central nervous system (CNS) has been noted. In British Columbia (population 4 million), a central database for lymphomas has allowed us to accurately track cases of paranasal sinus lymphoma diagnosed since 1980. A retrospective review was performed on the 44 patients who presented with primary paranasal sinus lymphoma (stage I or II) between 1980 and 1999. Histologic features were identified and immunophenotypic classification performed. Complete diagnostic and follow-up data including stage, treatment, response rates, sites of relapse and survival data were available for all patients. There were 26 men and 18 women. The types of lymphoma found were: diffuse large B cell (including immunoblastic), n = 37 (84%); T/NK nasal type, n = 3 (8%); peripheral T cell, not otherwise classified, n = 2 (4%); and others, n = 2 (4%). The median age at presentation was 66 years (range 27-97 years). The median follow-up for living patients was 114 months. For all 44 patients, the 5- and 10-year overall survivals were 48% and 41% and the disease-specific survivals 62% and 62%, respectively. Beginning in May 1985, intrathecal chemotherapy was added to our standard treatment plan of multi-agent chemotherapy and local irradiation. Before 1985, 2 of 5 patients developed leptomeningeal metastasis. Following the institution of intrathecal chemotherapy, only 8% (3 of 39) of patients have developed CNS disease. Introduction of intrathecal chemoprophylaxis was also associated with an improvement in overall survival from 20% to 51% and disease-specific survival from 40% to 65%. Primary paranasal sinus lymphoma is an uncommon presentation of lymphoma that carries the potential risk of spreading to the leptomeninges. Treatment with combined modality chemotherapy and irradiation can cure many patients and the addition of intrathecal chemotherapy may reduce the risk of CNS relapse.

Adult↗
PubMed2005

Allogeneic haematopoietic stem-cell transplantation for relapsed and refractory aggressive histology non-Hodgkin lymphoma.

Forty-four patients with relapsed or refractory aggressive histology non-Hodgkin lymphoma (NHL) (diffuse large B cell, n = 23; peripheral T cell, n = 5; transformed B cell, n = 16) proceeded to allogeneic stem cell transplant (allo-SCT) between 1987 and 2003. Median age at transplant was 40 years (range 19-56 years). At the time of transplant, 35 were chemosensitive and nine were chemorefractory. Thirty-three patients had matched sibling donors and 11 had unrelated donors. Forty-two patients (95%) received radiation-based conditioning regimens. Event-free survival (EFS) and overall survival (OS) at 5 years was 43% [95% confidence interval (CI): 27-58%] and 48% (95% CI: 32-63%) respectively. Treatment-related mortality was 25% at 1 year. Grade III-IV acute graft-versus-host disease (GVHD) was the only significant variable affecting OS and EFS, and had a negative impact. Chronic GVHD did not influence survival. Lymphoma relapse <12 months after initial therapy predicted for increased risk of relapse post-transplant (P = 0.02). Patients with chemorefractory lymphoma were not at increased risk of relapse (P = 0.20) with four of nine patients remaining alive without disease 12-103 months post-transplant. In conclusion, allo-SCT for relapsed or refractory aggressive histology NHL results in long-term EFS and OS of 40-50%. Patients with chemorefractory disease can have a durable remission post-transplant.

Adolescent↗
PubMed2005

Evolving approaches to primary treatment of Hodgkin lymphoma.

Two challenges confront the clinician treating Hodgkin lymphoma today: achieving a high level of effectiveness while minimizing toxicity. At least 80% of patients can be cured with currently available chemotherapy regimens, augmented in selected patients with the addition of involved field radiation or intensified chemotherapy assisted by granulocyte growth factors or stem cell transplantation. Major late toxicity including infertility, premature menopause, cardiovascular disease and second neoplasms can be avoided in most patients if the treatment program is chosen carefully. The extent of disease (stage) and, for advanced stage lymphoma, the presence of well-characterized prognostic factors can be established with readily available clinical, laboratory and imaging techniques. Results from carefully designed and analyzed clinical trials have identified optimal treatment approaches for patients with limited and advanced stage disease. Those with limited stage Hodgkin lymphoma should be treated with brief chemotherapy, only augmented with involved field irradiation if an early complete remission is not achieved. Most patients with advanced stage lymphoma can be cured with an extended course of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). The small minority under the age of 60 years with an International Prognostic Factors Project score of 5 or greater should be considered for intensified chemotherapy. Patients known to have bulky tumor(s) (> 10 cm) at diagnosis may require adjuvant irradiation at the conclusion of chemotherapy, but its utility has not been unequivocally established and radiation should be avoided in those who achieve a complete remission, where it is known to be ineffective. With careful selection of treatment program most patients found to have Hodgkin lymphoma today can be offered a high probability of cure and a low likelihood of major late toxicity. However, without detailed attention to the extent of lymphoma and other prognostic factors, there is as much danger of over-treatment as under-treatment. Only by thoughtfully adjusting the treatment program to the extent of disease and response to treatment can the clinician determine the optimal approach, maximizing likelihood of cure and minimizing late toxicity.

Adult↗
PubMed2005

Treatment of aggressive non-Hodgkin's lymphoma: a north American perspective.

The most common subtype of aggressive non-Hodgkin's lymphoma is diffuse large B-cell lymphoma (DLBCL). Diffuse large B-cell lymphoma represents a heterogeneous entity, with 5-year overall survival rates ranging from 26% to 73%. Microarray gene expression studies have confirmed that biologically distinct subgroups exist within DLBCL, and can be correlated with outcome. Initial management is usually guided by stage of disease at presentation. Approximately 25% of patients with DLBCL present with limited-stage disease and are treated with combined-modality therapy (brief chemotherapy and involved-field radiation). Most patients present with advanced-stage disease and require treatment with an extended course of chemotherapy. The CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone) chemotherapy regimen has been the mainstay of therapy since its development in the 1970s, as more intensive chemotherapy regimens failed to show additional benefit. The era of monoclonal antibodies has transformed treatment practices for aggressive lymphoma and has led to a significant improvement in outcome. A randomized trial comparing the use of rituximab (Rituxan), a chimeric anti-CD20 IgG1 monoclonal antibody, combined with CHOP chemotherapy vs CHOP chemotherapy alone for elderly patients with advanced-stage DLBCL demonstrated a significant benefitfor the combination approach. This finding has now been confirmed in two additional randomized, controlled trials and a population-based analysis, making CHOP and rituximab the standard of care for all newly diagnosed patients with DLBCL. Despite this advance, newer therapies are needed and many are under active investigation. The insights gained from molecular techniques such as gene expression profiling should permit identification of additional lymphoma-specific therapeutic targets and the development of novel agents that take into account underlying biology and allow for greater tailoring of therapy.

Antibodies, Monoclonal↗
PubMed2005

Vaccine therapy for non-Hodgkin's lymphoma and other B-cell malignancies.

Immunity against tumor antigens, including the passive transfer of humoral (antibody-based) immunity or cellular immunity in the form of cytotoxic T-lymphocyte clones, has been exploited for the treatment of non-Hodgkin's lymphoma and other B-cell malignancies in recent years. In many strategies, the idiotype expressed on B-cell malignancies is the antigen used to induce active immunity. Early studies using purified idiotype, immune adjuvant and cytokines to induce anti-idiotype immunity have demonstrated that these methods are safe and potentially effective, and they are now being tested in prospective, randomized clinical trials. Methods for improvement include recombinant sources of idiotype, DNA vectors, enhancement of antigen delivery and presentation by using dendritic cells, boosting immune help through the use of cytokine delivery or foreign antigens, and blocking negative regulators. The goal of this approach is to induce lasting and individualized immunity against B-cell malignancies that is readily available and cost-effective.

Animals↗
PubMed2004

Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells.

BACKGROUND: Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. METHODS: Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. RESULTS: Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. CONCLUSIONS: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.

Adult↗
PubMed2004

Identification of cytogenetic subgroups and karyotypic pathways of clonal evolution in follicular lymphomas.

Follicular lymphoma (FL) is characterized by the activation of BCL2 through t(14;18)(q32;q21). Additional acquired mutations are necessary to generate a fully malignant clonal proliferation. Many of these secondary genetic alterations are visible in the clonal karyotype; however, the sequence by which they arise and their influence on clinical behavior have not been determined. The ability to address these issues has been hampered by the lack of computational methods to manipulate complex chromosomal data in a sufficiently large cohort of cases. In the present investigation, we analyzed secondary karyotypic alterations in 336 cases of FL with t(14;18) to identify the most common regions of recurrent chromosomal gain or loss. This revealed 29 recurrent changes present in more than 5% of the tumors. Each tumor karyotype was then assessed for the presence or absence of each of these 29 specific changes. By statistical means, we show that the chromosomal changes arise in an apparent temporal order, with distinct early and late changes. We identify, by principal-components analysis, four possible cytogenetic pathways that characterize the early stages of clonal evolution, which converge to a common route at later stages. We show that FLs with t(14;18) may be classified into cytogenetic subgroups determined by the presence or absence of 6q-, +7, or der(18)t(14;18). Correlation with clinical outcomes in a subset of cases with clinical data revealed del(17p) and +12 to be correlated with an adverse clinical outcome. The clinical implications of these pathways of clonal evolution need to be examined on a prospective basis in a large cohort of FLs.

Chromosome Aberrations↗
PubMed2004

Delineation of a minimal region of deletion at 6q16.3 in follicular lymphoma and construction of a bacterial artificial chromosome contig spanning a 6-megabase region of 6q16-q21.

Regional deletions of 6q are frequent karyotypic alterations in malignant lymphoma and are associated with an adverse clinical outcome. One such region of recurrent deletion is 6q16-q21; however, the specific genes affected have not been identified. Our objective in this study was to identify cases with deletion of 6q16-q21 in follicular lymphoma and to define a minimal region of deletion. A physical map of 6q16.2-q21 was constructed using map information from both sequence-based and bacterial artificial chromosome (BAC) fingerprint-based maps. Forty-three BAC clones spanning a 6-Mb region of 6q16.2-q21 were identified and obtained from the RP-11 library. Selected BACs were fluorescence-labeled and hybridized to a series of 34 follicular lymphomas with a regional 6q deletion detected by G banding. Twenty-four cases with deletion of the 6q16.3 region were detected. A minimal deletion of 2.3 Mb was defined. Our study has identified a limited region of deletion of 6q16.3 that may implicate four known genes in follicular lymphoma and possibly in other cancers. A BAC contig spanning a 6-Mb region has been anchored to the 6q16.2-q21 region. This map represents a useful resource for gene identification in this region, not only in lymphoma but also in other neoplasms with 6q alterations.

Chromosome Deletion↗
PubMed2004

BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma.

Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed prognostically important subgroups: germinal center B-cell-like (GCB) DLBCL, activated B cell-like (ABC) DLBCL, and primary mediastinal large B-cell lymphoma. The t(14;18)(q32;q21) has been reported previously to define a unique subset within the GCB-DLBCL. We evaluated for the translocation in 141 cases of DLBCL that were successfully gene expression profiled. Using a dual-probe fluorescence in situ hybridization assay, we detected the t(14;18) in 17% of DLBCLs and in 34% of the GCB subgroup which contained the vast majority of positive cases. In addition, 12 t(14;18)-positive cases detected by polymerase chain reaction assays on additional samples were added to the fluorescence in situ hybridization-positive cases for subsequent analysis. Immunohistochemical data indicated that BCL2, BCL6, and CD10 protein were preferentially expressed in the t(14;18)-positive cases as compared to t(14;18)-negative cases. Within the GCB subgroup, the expression of BCL2 and CD10, but not BCL6, differed significantly between cases with or without the t(14;18): 88% versus 24% for BCL2 and 72% versus 32% for CD10, respectively. In the GCB-DLBCL subgroup, a heterogeneous group of genes is overexpressed in the t(14;18)-positive subset, among which BCL2 is a significant discriminator. Interestingly, the t(14;18)-negative subset is dominated by overexpression of cell cycle-associated genes, indicating that these tumors are significantly more proliferative, suggesting distinctive pathogenetic mechanisms. However, despite this higher proliferative activity, there was no significant difference in overall or failure-free survival between the t(14;18)-positive and -negative subsets within the GCB subgroup.

Apoptosis Regulatory Proteins↗
PubMed2004

The spectrum of lymphoma with 8q24 aberrations: a clinical, pathological and cytogenetic study of 87 consecutive cases.

To define the histologic, cytogenetic (CG) and clinical spectrum of non-Hodgkin lymphoma (NHL) carrying an 8q24 (c-myc) translocation, 87 patients with an 8q24 aberration were identified from 785 consecutive successfully analyzed cases. Aberrations involving 8q24 were found at diagnosis (n = 66) or at relapse/progression (n = 21). Histologically, Burkitt-like lymphoma (BLL) (32%) and Burkitt's leukemia/lymphoma (BL) (19%) with 8q24 changes at diagnosis, was the most common. Nevertheless, 46% of cytogenetically characterized BL and BLL cases do not show 8q24 aberrations. On the other hand, 8q24 aberration was also often found in follicular lymphoma (FL), mantle cell lymphoma (MCL) and low-grade NHL cases at progression. Cytogenetically, a de novo group is represented by classical t(8;14)(q24;q32) (n = 41), with isolated 8q24 changes, fewer secondary CG changes and represent mostly BL/BLL cases. In contrast, cases carrying variant 8q24 aberrations (n = 29) contain more CG events, carried primary 14q32 translocations, and included most FL, MCL and diffuse large B cell (DLBC) lymphoma cases. Clinically, the overall median follow-up was 8.6 months (range 0-192), with a median survival of 4.2 months from CG analysis. The presence of a 8q24 aberration give a statistically significant inferior prognosis than its absence in all histological groups, independent of clinical prognostic factors, when analyzed both at diagnosis and at relapse. We conclude that the finding of an 8q24 aberration is of marked negative prognostic significance, either at diagnosis or at disease progression, in a variety of NHL.

Adolescent↗
PubMed2004

Long-term disease-free survival of patients with advanced follicular lymphoma after allogeneic bone marrow transplantation.

Myeloablative allogeneic bone marrow transplantation (BMT) may be curative in patients with follicular non-Hodgkin's lymphoma, however, the impact of this therapy on long-term survival, disease progression and functional status is less clear. Twenty-nine patients (median age 42 years, range: 20-53) with advanced stage follicular lymphoma proceeded to allogeneic BMT a median of 25 (range: 8-154) months postdiagnosis, between 1985 and 2001, and have been followed for a minimum of 2 years. Eleven of 29 (38%) had refractory disease (n = 5 induction failure, n = 6 resistant relapse). Most (27 of 29, 93%) received total body irradiation-based conditioning; stem cell source was marrow from a related donor (n = 20) or unrelated donor (n = 9). Seventeen of 29 patients (59%) were alive a median of 5 years (range: 2-11) post-BMT with a median Karnofsky Performance Score of 100%. Death occurred because of transplant complications in seven patients (cumulative incidence of non-relapse mortality 24%), and progressive lymphoma in five patients (cumulative incidence of refractory/recurrent lymphoma 23%). The 5-year probability of overall and event-free survival was 58% and 53% respectively. Allogeneic BMT has resulted in long-term disease-free survival for approximately 50% of this cohort of patients with advanced follicular lymphoma and most of them now enjoy robust health.

Adult↗
PubMed2003

Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray.

Diffuse large B-cell lymphoma (DLBCL) can be divided into prognostically important subgroups with germinal center B-cell-like (GCB), activated B-cell-like (ABC), and type 3 gene expression profiles using a cDNA microarray. Tissue microarray (TMA) blocks were created from 152 cases of DLBCL, 142 of which had been successfully evaluated by cDNA microarray (75 GCB, 41 ABC, and 26 type 3). Sections were stained with antibodies to CD10, bcl-6, MUM1, FOXP1, cyclin D2, and bcl-2. Expression of bcl-6 (P <.001) or CD10 (P =.019) was associated with better overall survival (OS), whereas expression of MUM1 (P =.009) or cyclin D2 (P <.001) was associated with worse OS. Cases were subclassified using CD10, bcl-6, and MUM1 expression, and 64 cases (42%) were considered GCB and 88 cases (58%) non-GCB. The 5-year OS for the GCB group was 76% compared with only 34% for the non-GCB group (P <.001), which is similar to that reported using the cDNA microarray. Bcl-2 and cyclin D2 were adverse predictors in the non-GCB group. In multivariate analysis, a high International Prognostic Index score (3-5) and the non-GCB phenotype were independent adverse predictors (P <.0001). In summary, immunostains can be used to determine the GCB and non-GCB subtypes of DLBCL and predict survival similar to the cDNA microarray.

Adolescent↗
PubMed2003

Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma.

Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.

Adult↗
PubMed2003

Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients.

PURPOSE: Standard therapies for non-Hodgkin's lymphoma (NHL) are associated with an increased risk of developing treatment-related myelodysplastic syndrome or acute myelogenous leukemia (tMDS/AML). However, there is considerable debate over the incidence or risk of tMDS/AML in NHL patients treated with any particular modality and the factors that contribute to malignant transformation. DESIGN: Conclusions were based on thorough analysis of data reported in the peer-reviewed literature and careful examination of the statistical methodology and methods for identifying cases of tMDS/AML. Unless noted, data are reported only for NHL patients, excluding Hodgkin's disease patients. RESULTS: Despite differences in methods used to identify cases and to estimate the cumulative incidence over time (actuarial v cumulative calculations), up to 10% of NHL patients treated with either conventional-dose chemotherapy or high-dose therapy and autologous stem-cell transplantation may develop tMDS/AML within 10 years of primary therapy. Kaplan-Meier estimates of the actuarial incidence, which are based on censoring of patients who died without developing tMDS/AML, can lead to artificially high estimates with large confidence intervals at later time points. Although there is much debate about the cause(s) of tMDS/AML, there is compelling evidence that alkylating agents, certain other leukemogenic agents, and total-body irradiation (TBI) cause chromosomal damage that can lead to tMDS/AML. CONCLUSION: Limiting exposure to alkylating agents and eliminating TBI from transplantation conditioning regimens may reduce the relative risk of tMDS/AML.

Acute Disease↗
PubMed2003

Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial.

PURPOSE: In a series of trials, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV) have been identified as effective treatments for Hodgkin's disease. We compared these regimens as initial chemotherapy for Hodgkin's disease. PATIENTS AND METHODS: Adult patients (N = 856) with advanced Hodgkin's disease were randomly assigned to treatment with ABVD or MOPP/ABV. The major end points were failure-free and overall survival, life-threatening acute toxicities, and serious long-term toxicities, including cardiomyopathy, pulmonary toxicity, myelodysplastic syndromes (MDS), and secondary malignancies. RESULTS: The rates of complete remission (76% v 80%, P =.16), failure-free survival at 5 years (63% v 66%, P =.42), and overall survival at 5 years (82% v 81%, P =.82) were similar for ABVD and MOPP/ABV, respectively. Clinically significant acute pulmonary and hematologic toxicity were more common with MOPP/ABV (P =.060 and.001, respectively). There was no difference in cardiac toxicity. There were 24 deaths attributed to initial treatment: nine with ABVD and 15 with MOPP/ABV (P =.057). There have been 18 second malignancies associated with ABVD and 28 associated with MOPP/ABV (P =.13). Thirteen patients have developed MDS or acute leukemia: 11 were initially treated with MOPP/ABV, and two were initially treated with ABVD but subsequently received MOPP-containing regimens and radiotherapy before developing leukemia (P =.011). CONCLUSION: ABVD and the MOPP/ABV hybrid are effective therapies for Hodgkin's disease. MOPP/ABV is associated with a greater incidence of acute toxicity, MDS, and leukemia. ABVD should be considered the standard regimen for treatment of advanced Hodgkin's disease.

Adult↗
PubMed2003

Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy.

PURPOSE: A phase II trial was performed to evaluate the efficacy, tolerance, and pharmacokinetic profiles of oral vinorelbine (Navelbine). Oral Navelbine (NVB; Pierre Fabre Médicament, Boulogne, France) was given as first-line chemotherapy for locally advanced or metastatic breast carcinoma (ABC). PATIENTS AND METHODS: Sixty-four patients were entered to receive oral NVB on a weekly basis for a total of 8 weeks unless progression or toxicity occurred. Oral NVB was given at 60 mg/m(2) weekly for the first three administrations and was increased to 80 mg/m(2) for the subsequent administrations if there was no grade 4 neutropenia or no more than one episode of grade 3 neutropenia. Patients with objective response or stable disease continued treatment up to a total of 12 weeks or more. RESULTS: Fifty-eight evaluable patients were included in our study. Four patients (6.9%) had complete responses, and 14 (24.1%) had partial responses, for an overall response rate of 31% (95% CI, 19% to 43%). Median progression-free survival was 17.4 weeks. Median overall survival is not yet reached. There were no treatment-related deaths. The main toxicity was neutropenia: grade 4 in 17.2% of the patients, and 1.8% of administrations and associated clinical serious events in 4 patients (6.2%). Grade 3 and 4 nausea and/or vomiting were noted in 3.1% and 4.6% of the patients, respectively. Only one patient developed grade 3 neuroconstipation. An analysis of Quality of Life Questionnaire C30 forms revealed no significant alteration between baseline and weeks 8 and 16 in global quality of life. CONCLUSION: Oral NVB at this schedule is an effective and well-tolerated agent in the treatment of ABC and offers a promising alternative to the intravenous route. Combination studies are ongoing.

Administration, Oral↗