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James L Murray

Publications and source records attributed to James L Murray.

23 records · Page 2Linked to original sources
PubMed2002

Phase I study of vinorelbine and docetaxel with granulocyte colony-stimulating factor support in the treatment of metastatic breast cancer.

PURPOSE: Vinorelbine and docetaxel are two active agents in the treatment of metastatic breast cancer. When given together, these drugs exhibit synergistic antitumor activity without significant pharmacokinetic interaction. The dose-limiting toxicities of this combination are neutropenic fever and mucositis. Adding granulocyte colony-stimulating factor (G-CSF) might lessen the toxicity and increase the maximum tolerated dose (MTD) of this combination. The aim of this study was to determine the MTD of vinorelbine and docetaxel given in combination with G-CSF. PATIENTS AND METHODS: Between August 1997 and December 1998, 14 patients with metastatic breast cancer were enrolled in this study. All patients had received doxorubicin-based therapy, and 46% had received paclitaxel in the adjuvant or neoadjuvant setting. Patients were treated with vinorelbine at a starting dose of 20 mg/m2 intravenously over 10 min on days 1 and 5 and docetaxel at a starting dose of 85 mg/m2 intravenously over 1 hr on day 1, following the vinorelbine. Treatments were repeated every 21 days. Prophylactic G-CSF 5 mcg/kg was given subcutaneously on days 3-10. Toxicity was graded according to the National Cancer Institute's grading system. RESULTS: A total of 65 cycles was administered at dose levels 0, -1, -2, and -3. The median absolute granulocyte count nadir for all courses was 200 mm(-3) (range, 0.1-7700 mm(-3)), and the median time to this nadir was 9 days (range, 7-30). The median platelet nadir was 163 (range, 27-401 k), and the median time to this nadir was 8 days (range, 7-30). The most common grade 3 nonhematologic toxicities for all courses were fatigue and myalgia, which occurred in 32 and 10 cycles, respectively. Neutropenic fever was encountered in 11 cycles. Three patients developed colitis-like pictures, two of whom died as a result. Consequently, the protocol was closed to accrual before a MTD was reached. CONCLUSION: The combination of vinorelbine, docetaxel, and G-CSF in our hands has proven to be a toxic regimen, even when relatively low doses of vinorelbine and docetaxel are given. Meticulous observation of patients receiving this combination is warranted since the combination resulted in two deaths in this study.

Adult↗
PubMed2002

Axillary lymph node cellular immune response to HER-2/neu peptides in patients with carcinoma of the breast.

HER-2/neu peptides have recently been shown to induce a proliferative response by peripheral CD4(+) T cells in breast cancer patients. To investigate potential differences in the local cellular immune response between breast cancer patients with and without nodal metastases, lymphocytes were isolated from axillary lymph nodes from patients with breast cancer, and proliferative and cytokine responses to HER-2/neu peptides were determined. Freshly isolated lymphocytes from lymph nodes of 7 women undergoing surgery for invasive breast cancer were plated at 20 x 10(5) cells per well in triplicate. Cells were stimulated with HER-2/neu peptides at 50 microg/ml and with control antigens. Incorporation of tritium-labeled thymidine was determined 4 days later. The levels of the cytokines interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-10 were determined at priming and at restimulation with HER-2/neu peptides using a cytokine-specific, double-sandwich, enzyme-linked immunosorbent assay (ELISA). Lymphocytes isolated from the axillary lymph nodes of the patients mounted significant cellular immune response to HER-2/neu peptides, manifested by proliferation and specific cytokine elaboration. Proliferative responses to HER-2/neu peptides were seen in lymphocytes of patients with and without overexpression of HER-2/neu in the primary tumor. In some patients, the proliferative response to HER-2/neu peptides in lymphocytes from lymph nodes with metastases was absent or blunted compared with the response in lymphocytes from lymph nodes without metastases from the same patient (p < 0.05). HER-2/neu peptides induced a predominantly T helper type 1 (Th1) pattern of cytokine response in nodal lymphocytes isolated from breast cancer patients. A Th1-specific cytokine production pattern was maintained at priming and restimulation with HER-2/neu peptides and was amplified with IL-12 costimulation. These results indicate that HER-2/neu peptides can activate T cells in draining lymph nodes from women with invasive breast cancer. This activation is associated with a predominantly Th1 cytokine response, which suggests that conditioning with HER-2/neu peptides may be of value in the development of breast cancer vaccines.

Antigens, Neoplasm↗
PubMed2002

A detailed evaluation of cardiac toxicity: a phase II study of doxorubicin and one- or three-hour-infusion paclitaxel in patients with metastatic breast cancer.

PURPOSE: This Phase II study was designed to determine the efficacy and toxicity of combination doxorubicin and paclitaxel as front-line treatment for metastatic breast cancer. EXPERIMENTAL DESIGN: Eligible patients had no prior anthracycline or taxane therapy and normal cardiac function. They were treated with bolus doxorubicin 60 mg/m2, followed by paclitaxel 200 mg/m2, as either 1- or 3-h infusions for six to seven cycles. Single-agent paclitaxel was continued thereafter. Serial multiple gated acquisition scans were performed, and endomyocardial biopsies were performed for consenting patients. RESULTS: Eighty-two patients were enrolled with a median age of 53 years (range, 32-78 years). Of 79 evaluable patients, 58.2% had an objective response (3.8% complete response + 54.4% partial response), 34.2% had stable disease, and 7.6% had progressive disease. With median follow-up of 37.5 months, median time to progression was 7 months; median survival was 31 months. Multiple gated acquisition scans were performed in 82 of 82 patients at baseline, 75 of 82 patients at a total doxorubicin dose of 60-180 mg/m2, 62 of 68 patients at 200-300 mg/m2, 18 of 52 patients at 310-360 mg/m2, and 4 of 8 patients at 420 mg/m2. Median ejection fractions were 62.5, 60, 57.5, 52.5, and 32%, respectively. Fifteen of 82 (18.3%) patients had a decrease in ejection fraction > or = 15% to an absolute ejection fraction < or = 50%. Eight of these 15 patients (53%) developed clinical congestive heart failure: 4 of 8 (50%) who received a total doxorubicin dose of 420 mg/m2 versus 4 of 74 (5.4%) who received a dose < or = 360 mg/m2 (P = 0.002). CONCLUSIONS: When the doxorubicin dose exceeds 360 mg/m2, the combination of bolus doxorubicin and paclitaxel presents unacceptable cardiac risk.

Adult↗
PubMed2002

Toxicity, immunogenicity, and induction of E75-specific tumor-lytic CTLs by HER-2 peptide E75 (369-377) combined with granulocyte macrophage colony-stimulating factor in HLA-A2+ patients with metastatic breast and ovarian cancer.

To determine the toxicity and immunogenicity of the HER-2/neu, HLA-A2-restricted peptide E75 in patients with metastatic breast and ovarian cancer, 14 patients were vaccinated with escalating amounts of E75 (100, 500, and 1000 microg) mixed with 250 microg granulocyte macrophage colony-stimulating factor as adjuvant. Each vaccine dose was administered in a total volume of 1.5 ml divided into four intradermal injections and administered weekly for 4 weeks, followed by monthly boosts for a total of 10 injections. Vaccinations were well tolerated without significant toxicity. Blood was drawn before, at 8 weeks, and up to 13-16 months after vaccination for measurement of cellular immunity. Seven of 8 patients tested had significant delayed type hypersensitivity to E75 defined as >5 mm induration. Peripheral blood mononuclear cells from 5 of 9 patients tested proliferated to E75 with a stimulation index of > or = 2.0. Of 8 vaccinated patients tested for induction of a CTL response, 4 responded to stimulation by autologous dendritic cells plus cytokines by eliciting E75-specific lytic activity consistent with the presence of activated/memory cells, 2 others after in vitro stimulation with E75 + interleukin-12 +/- anti-CD152(33KD), whereas 2 others did not respond. Four patients with E75-specific CTLs present specifically recognized E75 on indicator tumors as demonstrated by cold-target inhibition of tumor lysis. These 4 patients showed E75-specific IFN-gamma production. peripheral blood mononuclear cell from 3 of these patients proliferated to E75, but stimulation indices were higher in the prevaccine samples. All 4 of the patients showed DTH responses to E75. These results demonstrate that vaccination with E75+ granulocyte macrophage colony-stimulating factor can induce both peptide-specific IFN-gamma and epitope specific CTLs, which lyse HER-2/neu+ tumors in stage IV patients.

Abatacept↗