Barbara Grant

University of Vermont, Burlington, Vermont, United States

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Publications (2)35.76 Total impact

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    ABSTRACT: A multicenter phase II study was conducted to assess the efficacy of rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy (rdWBRT) and cytarabine in primary CNS lymphoma. Patients received induction chemotherapy with R-MPV (five to seven cycles); those achieving a complete response (CR) received rdWBRT (23.4 Gy), and otherwise, standard WBRT was offered (45 Gy). Consolidation cytarabine was given after the radiotherapy. The primary end point was 2-year progression-free survival (PFS) in patients receiving rdWBRT. Exploratory end points included prospective neuropsychological evaluation, analysis of magnetic resonance imaging (MRI) white matter changes using the Fazekas scale, and evaluation of the apparent diffusion coefficient (ADC) as a prognostic factor. Fifty-two patients were enrolled, with median age of 60 years (range, 30 to 79 years) and median Karnofsky performance score of 70 (range, 50 to 100). Thirty-one patients (60%) achieved a CR after R-MPV and received rdWBRT. The 2-year PFS for this group was 77%; median PFS was 7.7 years. Median overall survival (OS) was not reached (median follow-up for survivors, 5.9 years); 3-year OS was 87%. The overall (N = 52) median PFS was 3.3 years, and median OS was 6.6 years. Cognitive assessment showed improvement in executive function (P < .01) and verbal memory (P < .05) after chemotherapy, and follow-up scores remained relatively stable across the various domains (n = 12). All examined MRIs (n = 28) displayed a Fazekas score of ≤ 3, and no patient developed scores of 4 to 5; differences in ADC values did not predict response (P = .15), PFS (P = .27), or OS (P = .33). R-MPV combined with consolidation rdWBRT and cytarabine is associated with high response rates, long-term disease control, and minimal neurotoxicity.
    Journal of Clinical Oncology 10/2013; DOI:10.1200/JCO.2013.50.4910 · 17.88 Impact Factor
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    ABSTRACT: Our goals were to evaluate the safety of adding rituximab to methotrexate (MTX)-based chemotherapy for primary CNS lymphoma, determine whether additional cycles of induction chemotherapy improve the complete response (CR) rate, and examine effectiveness and toxicity of reduced-dose whole-brain radiotherapy (WBRT) after CR. Thirty patients (17 women; median age, 57 years; median Karnofsky performance score, 70) were treated with five to seven cycles of induction chemotherapy (rituximab, MTX, procarbazine, and vincristine [R-MPV]) as follows: day 1, rituximab 500 mg/m2; day 2, MTX 3.5 gm/m2 and vincristine 1.4 mg/m2. Procarbazine 100 mg/m2/d was administered for 7 days with odd-numbered cycles. Patients achieving CR received dose-reduced WBRT (23.4 Gy), and all others received standard WBRT (45 Gy). Two cycles of high-dose cytarabine were administered after WBRT. CSF levels of rituximab were assessed in selected patients, and prospective neurocognitive evaluations were performed. With a median follow-up of 37 months, 2-year overall and progression-free survival was 67% and 57%, respectively. Forty-four percent of patients achieved a CR after five or fewer cycles, and 78% after seven cycles. The overall response rate was 93%. Nineteen of 21 CR patients received the planned 23.4 Gy WBRT. The most commonly observed grade 3 to 4 toxicities included neutropenia (43%), thrombocytopenia (36%), and leukopenia (23%). No treatment-related neurotoxicity has been observed. The addition of rituximab to MPV increased the risk of significant neutropenia requiring routine growth factor support. Additional cycles of R-MPV nearly doubled the CR rate. Reduced-dose WBRT was not associated with neurocognitive decline, and disease control to date is excellent.
    Journal of Clinical Oncology 11/2007; 25(30):4730-5. DOI:10.1200/JCO.2007.12.5062 · 17.88 Impact Factor