Biomedical subjects

Vicki A Morrison

Publications and source records attributed to Vicki A Morrison.

13 recordsLinked to original sources

PubMed2006

Telephone monitoring of distress in patients aged 65 years or older with advanced stage cancer: a cancer and leukemia group B study.

BACKGROUND: Significant barriers to cancer patients receiving mental health treatment for distress have been reported in the literature. The objective of the current study was to determine whether distress in older patients (aged 65 years and older) would be reduced with educational materials (EM) supplemented by monthly telephone monitoring (TM) (TM + EM) compared with the use of EM alone because of more timely referrals to appropriate health professionals. METHODS: One hundred ninety-two older patients with breast, prostate, and colorectal cancers who had advanced disease and currently were receiving treatment were randomized to receive either TM + EM or EM alone. One hundred thirty-one patients were evaluated by telephone interview for psychologic and physical distress and for social support at baseline and at 6 months using the Hospital Anxiety and Depression Scale (HADS), the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C30 quality-of-life questionnaire, and the Medical Outcomes Study (MOS) Social Support Survey. Patients who in the TM + EM group were called monthly for 6 months to monitor their distress using the HADS and EORTC physical symptom items and the MOS Social Support Survey items, with cutoff levels were established to indicate which patients were in greater distress. Those patients who scored above the cutoff levels were referred to their oncology nurse for referral to the appropriate professional. Patients in the EM group received written materials regarding cancer-related psychosocial issues and available resources. RESULTS: At 6 months, patients in the TM + EM group reported significantly less anxiety (HADS; P < .0001), depression (HADS; P = .0004), and overall distress (HADS; P < .0001) compared with patients in the EM group. CONCLUSIONS: Monthly monitoring of older patients' distress with TM and EM along with referral for appropriate help was found to be an efficient means of reducing patients' anxiety and depression compared with patients who received only EM.

Adaptation, Psychological↗

PubMed2006

Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma.

PURPOSE: To address early and late treatment failures in older patients with diffuse large B-cell lymphoma (DLBCL), we designed a two-stage randomized trial of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus rituximab plus CHOP (R-CHOP), with a second random assignment to maintenance rituximab (MR) or observation in responding patients. PATIENTS AND METHODS: Untreated DLBCL patients who were 60 years or older were randomly assigned to R-CHOP (n = 318) or CHOP (n = 314); 415 responders were randomly assigned to MR (n = 207) or observation (n = 208). The primary end point was failure-free survival (FFS). All P values were two sided. RESULTS: Three-year FFS rate was 53% for R-CHOP patients and 46% for CHOP patients (P = .04) at a median follow-up time of 3.5 years. Two-year FFS rate from second random assignment was 76% for MR compared with 61% for observation (P = .009). No significant differences in survival were seen according to induction or maintenance therapy. FFS was prolonged with MR after CHOP (P = .0004) but not after R-CHOP (P = .81) with 2-year FFS rates from second random assignment of 77%, 79%, 74%, and 45% for R-CHOP, R-CHOP + MR, CHOP + MR, and CHOP, respectively. In a secondary analysis excluding MR patients, R-CHOP alone reduced the risks of treatment failure (P = .003) and death (P = .05) compared with CHOP alone. CONCLUSION: Rituximab administered as induction or maintenance with CHOP chemotherapy significantly prolonged FFS in older DLBCL patients. After R-CHOP, no benefit was provided by MR. These results, which are consistent with an additive effect of rituximab, suggest that future studies could focus on maintenance strategies with novel agents as well as new induction therapies.

Age Factors↗

PubMed2006

Infectious complications of chronic lymphocytic leukemia.

Infectious complications continue to be one of the major causes of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). The pathogenesis of infections in these patients is multifactorial. Hypogammaglobulinemia is an important predisposing factor for infection in patients with early-stage disease and for those treated with conventional alkylating agents. However, the proportion of patients treated with purine analogs and monoclonal antibodies such as rituximab and alemtuzumab is increasing. As a result of this therapy, these patients often experience profound and sustained T-cell immunodeficiency. Consequently, the spectrum of organisms causing infections in these patients is changing from common bacterial organisms to less common opportunistic pathogens such as Pneumocystis, Listeria, mycobacteria, herpesviruses, and Candida. This review focuses on the pathogenesis and risk factors for infections in patients with CLL, the spectrum of infectious organisms associated with the newer agents, and the management of these infections with an emphasis on prophylaxis and vaccination strategies.

Antineoplastic Agents↗

PubMed2006

Echinocandin antifungals: review and update.

The echinocandins are a new and unique class of antifungal agents that act on the fungal cell wall by way of noncompetitive inhibition of the synthesis of 1,3-beta-glucans. All agents of this class are of parenteral formulation, with no oral preparations available. Caspofungin (Cancidas) was the first approved echinocandin, followed recently by micafungin (Mycamine) and anidulafungin (Eraxis). The precise role of the echinocandins in the antifungal armamentarium is still unfolding. Caspofungin is approved for the treatment of candidal esophagitis and candidemia, salvage therapy of Aspergillus infections and for empirical therapy of febrile neutropenia. Micafungin is likewise approved for candidal esophagitis, in addition to antifungal prophylaxis for hematopoietic stem cell transplant recipients. Anidulafungin is also approved for treatment of candidal esophagitis, as well as therapy of candidemia. There has been anecdotal use of these agents to treat less common fungal pathogens, as well as limited use as a component of combination antifungal therapy. The echinocandins are an important addition to the antifungal armamentarium in the treatment of fungal infections in both immunocompromised patients and those with normal immunity.

Anidulafungin↗

PubMed2005

Rituximab therapy is effective for posttransplant lymphoproliferative disorders after solid organ transplantation: results of a phase II trial.

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLD) remain an uncommon complication of solid organ transplantation with a high mortality rate reported after conventional therapies. Alternative treatments such as rituximab have been explored. METHODS: Eleven patients with PTLD, who were CD20 positive, received an intravenous dose of rituximab, 375 mg/m2, weekly x 4 weeks, repeated every 6 months for 2 years in responding patients. The median age of the patients was 56 years (range, 43-68 yrs), and 9 patients were male. The type of solid organ transplantation that these patients received included lung (five patients), kidney (four patients), heart (one patient), and kidney/pancreas (one patient). The median time from transplantation to a PTLD diagnosis was 9 months (range, 1-122 mos). Diagnostic B-cell histology was diffuse large cell lymphoma or polymorphous process. No patient had bone marrow or central nervous system involvement. Primary extranodal disease was noted in 82% of patients. Immunosuppressive therapy was decreased at the time of diagnosis. RESULTS: Rituximab was well tolerated, with mild infusional blood pressure alterations noted in two patients. The median follow-up period was 10 months (range, 1-32 mos). The overall response rate was 64%, with 6 complete responses (CR), 1 partial response, 2 cases of progressive disease, and 2 deaths. The median duration of CR was 8 months (range, 2-19+ mos). The median time to treatment failure was 10 months (range, 5-25+ mos). The median survival was 14 months (range, < 1-32+ mos). Four patients were alive at the time of last follow-up. CONCLUSIONS: Single-agent rituximab may offer a response and survival advantage in patients with PTLD. Further evaluation of rituximab in these disorders, potentially in combination with other therapies, is warranted.

Adult↗

PubMed2005

Caspofungin: an overview.

The echinocandins are a novel class of antifungal agents that have come into use over the past 10 years. The mechanism of action of these lipopeptide agents is via noncompetitive inhibition of the synthesis of 1,3-beta-glucans, which are fungal cell wall constituents. All agents of this class are only available in an intravenous formulation. The first approved agent of this class was caspofungin (Cancidas). Caspofungin is a therapeutic option for patients with candidal esophagitis and deep-seated candidal infections, and is an alternative therapy for Aspergillus infections, especially in the salvage setting. In addition, it is a therapeutic option for the empiric therapy of febrile neutropenia. The usefulness of this agent in treating less common fungal infections has been cited in anecdotal reports. One major limitation of this drug is the lack of an oral formulation. Caspofungin may be considered as a component of combination antifungal regimens. Caspofungin represents a significant advance in the care of patients with serious fungal infections.

Animals↗

PubMed2004

Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011.

Fludarabine and rituximab combination therapies in chronic lymphocytic leukemia (CLL) have yielded promising early results, but no comparative efficacy data relative to standard fludarabine treatment regimens have been reported. To assess the effect of the addition of rituximab to fludarabine therapy, we retrospectively compared the treatment outcome of patients with similar clinical characteristics enrolled on 2 multicenter clinical trials performed by the Cancer and Leukemia Group B and the US Intergroup that used fludarabine and rituximab (CALGB 9712, n = 104) or fludarabine (CALGB 9011, n = 178). In multivariate analyses controlling for pretreatment characteristics, the patients receiving fludarabine and rituximab had a significantly better progression-free survival (PFS; P < .0001) and overall survival (OS; P = .0006) than patients receiving fludarabine therapy. Two-year PFS probabilities were 0.67 versus 0.45, and 2-year OS probabilities were 0.93 versus 0.81. Infectious toxicity was similar between the 2 treatment approaches. These comparative data are retrospective and could be confounded by differences in supportive care or dissimilar enrollment of genetic subsets on each trial. Confirmation of these findings will require a prospective randomized trial comparing fludarabine and rituximab to fludarabine.

Adult↗

PubMed2003

Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin's lymphoma receiving CHOP chemotherapy.

We sought to identify risk factors associated with the time to febrile neutropenia in patients with intermediate-grade, non-Hodgkin's lymphoma (NHL) who were receiving treatment with CHOP chemotherapy. Data were collected from 12 community and academic oncology practices participating in the Oncology Practice Pattern Study between 1991 and 1999. We reviewed the medical records of 577 intermediate-grade NHL patients who received initial CHOP chemotherapy and evaluated risk factors associated with time to first febrile neutropenic event. A febrile neutropenic event was defined as a body temperature of > 100.6 degrees F and an ANC nadir < 1000/mm3. A total of 160 patients experienced 224 febrile neutropenic events. The risk of febrile neutropenia was significantly associated with age > or = 65 years (p = 0.001), cardiovascular disease (p = 0.020), renal disease (p = 0.006), baseline hemoglobin < 12 g/dl (p = 0.018), > 80% planned average relative dose intensity (ARDI; p = 0.018), and no prophylactic colony-stimulating factor (CSF) use (p = 0.046). First febrile neutropenic events occurred by day 14 of cycle 1 in one-half of patients experiencing febrile neutropenia. In multivariate analysis, the risk of febrile neutropenia remained significantly associated with age > or = 65 years (HR = 1.65, 95% CI: 1.18-2.32), renal disease (HR = 1.91. 95% CI: 1.10-3.30), cardiovascular disease (HR = 1.54, 95% CI: 1.02-2.33), baseline hemoglobin < 12 g/dl (HR = 1.44, 95% CI: 1.04-2.00), > 80% planned CHOP ARDI (HR = 2.41, 95% CI: 1.30-4.47), and no CSF prophylaxis (HR = 2.13, 95% CI: 1.20-3.76). Such a model may permit the identification of patients at greatest risk of febrile neutropenia and, therefore, candidates for the selective prophylactic use of the hematopoietic growth factors.

Adult↗

PubMed2002

Therapy-related myeloid leukemias are observed in patients with chronic lymphocytic leukemia after treatment with fludarabine and chlorambucil: results of an intergroup study, cancer and leukemia group B 9011.

PURPOSE: Patients with chronic lymphocytic leukemia (CLL) may have disease transformation to non-Hodgkin's lymphoma or prolymphocytic leukemia; however, development of therapy-related acute myeloid leukemia (t-AML) is unusual. A series of patients enrolled onto an intergroup CLL trial were examined for this complication. PATIENTS AND METHODS: A total of 544 previously untreated B-cell CLL patients were enrolled onto a randomized intergroup study comparing treatment with chlorambucil, fludarabine, or fludarabine plus chlorambucil. Case report forms from 521 patients were reviewed for t-AML. RESULTS: With a median follow-up of 4.2 years, six patients (1.2%) to date have developed therapy-related myelodysplastic syndrome (t-MDS; n = 3), t-AML (n = 2), or t-MDS evolving to t-AML (n = 1), from 27 to 53 months (median, 34 months) after study entry. This included five (3.5%) of 142 patients treated with fludarabine plus chlorambucil and one (0.5%) of 188 receiving fludarabine; no chlorambucil-treated patients developed t-MDS or t-AML (P =.007). At study entry, the median age among these six patients was 56 years (range, 44 to 72 years); three were male; the CLL Rai stage was I/II (n = 4) or III/IV (n = 2). Response to CLL therapy was complete (n = 4) or partial remission (n = 1) and stable disease (n = 1). Marrow cytogenetics, obtained in three of six cases at diagnosis of t-MDS or t-AML, were complex, with abnormalities in either or both chromosomes 5 and 7. Other abnormalities involved chromosomes X, 1, 8, 12, 17, and 19. Median survival after diagnosis of t-MDS/AML was 3.5 months (range, 0.5 to 10.1 months). CONCLUSION: Our findings raise the possibility that alkylator-purine analog combination therapy may increase the risk of therapy-related myeloid malignancies, which is of particular relevance with regard to ongoing trials using these combination therapies.

Acute Disease↗

PubMed2002

Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712).

Recent studies have suggested that rituximab has clinical activity and modulates antiapoptotic proteins associated with drug resistance in chronic lymphocytic leukemia (CLL). We performed a randomized phase 2 study to determine the efficacy, safety, and optimal administration schedule of rituximab with fludarabine in previously untreated CLL patients. Patients were randomized to receive either 6 monthly courses of fludarabine concurrently with rituximab followed 2 months later by 4 weekly doses of rituximab for consolidation therapy or sequential fludarabine alone followed 2 months later by rituximab consolidation therapy. A total of 104 patients were randomized to the concurrent (n = 51) and sequential (n = 53) regimens. During the induction portion of treatment, patients receiving the concurrent regimen experienced more grade 3 or 4 neutropenia (74% versus 41%) and grade 3 or 4 infusion-related toxicity (20% versus 0%) as compared with the sequential arm. The consolidation rituximab therapy was tolerated well in both arms. All other toxicities were similar in the 2 arms. The overall response rate with the concurrent regimen was 90% (47% complete response [CR], 43% partial response [PR]; 95% confidence interval [CI], 0.82-0.98) compared with 77% (28% CR, 49% PR; 95% CI, 0.66-0.99) with the sequential regimen. With a median follow-up time of 23 months, the median response duration and survival have not been reached for either regimen. Rituximab administered concurrently with fludarabine in previously untreated CLL patients demonstrates marked clinical efficacy and acceptable toxicity. Phase 3 studies using this combination approach for patients with CLL are warranted.

Adult↗

PubMed2002

Analysis of age, estimated creatinine clearance and pretreatment hematologic parameters as predictors of fludarabine toxicity in patients treated for chronic lymphocytic leukemia: a CALGB (9011) coordinated intergroup study.

PURPOSE: Fludarabine is a renally excreted agent that is an effective treatment for chronic lymphocytic leukemia (CLL), a disease predominantly of the elderly. We sought to determine whether age, renal function or pretreatment hematologic status predicted toxicity of fludarabine treatment for CLL. METHODS: We evaluated 192 patients with previously untreated B-cell CLL who were entered onto the fludarabine treatment arm (25 mg/m(2) daily for 5 days every 28 days) of CALGB study 9011, an intergroup study with participation from SWOG, CTG/NCI-C and ECOG. Patients were required to have serum creatinine within 1.5 times normal. Hematologic indices and infections were recorded during the first 28-day cycle of treatment. A time-to-toxicity endpoint was evaluated over the entire course of fludarabine treatment. Creatinine clearance (CrCl(est)) was estimated using serum creatinine, age and body mass index. RESULTS: The median age was 64 years (range 37-87 years) and median CrCl(est) was 62 ml/min (range 27-162 ml/min, interquartile range 52-79 ml/min). We found no association between age and incidence of hematologic toxicity or infection during the first cycle of treatment. There was a strong association between CrCl(est) and the time-to-toxicity endpoint. Patients with CrCl(est) below 80 ml/min had increased incidence of toxicity during their treatment course ( P<0.0001). Pretreatment anemia, thrombocytopenia and Rai stage were highly associated with the incidence of neutrophil toxicity and grade III/IV hematologic toxicities during the first cycle of treatment ( P<0.0001). CONCLUSIONS: Patient age was not an independent risk factor for fludarabine-related toxicity, but CrCl(est) was associated with time to toxicity.

Adult↗

PubMed2002

Emerging fungal pathogens in patients with hematologic malignancies and marrow/stem-cell transplant recipients.

Fungal infections are a major cause of morbidity and mortality among patients with hematologic malignancies and recipients of bone-marrow/hematopoietic stem-cell transplants. Although Candida and Aspergillus species remain the most common fungal pathogens, multiple unusual fungal pathogens are being increasingly recognized as a cause of infection in these patients. Many of these rare fungal infections have a characteristic clinical disease spectrum. Early diagnosis and prompt treatment of these infections is the key to a successful outcome. In this article, we summarize the epidemiology, pathogenesis, clinical features, and approach to the management of infections caused by Fusarium, Zygomycetes, Scedosporium, Trichosporon, Malassezia, Alternaria, Paecilomyces, and Penicillium.

Bone Marrow Transplantation↗

PubMed2002

The role of caspofungin and the echinocandins in the antifungal armamentarium.

The echinocandins are a recently-developed class of antifungal agents that interfere with fungal cell wall synthesis through the inhibition of glucan synthesis. Although several intravenous preparations are in various stages of development, caspofungin is the only currently approved agent and no oral echinocandin derivatives are presently available. Caspofungin is approved for the treatment of invasive aspergillosis in patients who are refractory to, or intolerant of, other antifungal therapies. This agent has activity against most Candida species, and in a prospective randomized trial, was as effective as, and better tolerated than amphotericin B in the treatment of candidal esophagitis. Activity against the cyst form of Pneumocystis carinii has also been demonstrated. Caspofungin is administered in a daily intravenous dose, and is well tolerated. Concomitant use of this agent with cyclosporine is presently not recommended. Other echinocandin derivatives presently in phase II/III clinical development include micafungin and anidulafungin.

Anti-Bacterial Agents↗