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Biomedical subjects

R Pelley

Publications and source records attributed to R Pelley.

8 recordsLinked to original sources
PubMed2000

A phase II pharmacodynamic study of pyrazoloacridine in patients with metastatic colorectal cancer.

PURPOSE: To perform a phase II trial of pyrazoloacridine (PZA), a novel DNA intercalator, in patients with metastatic colorectal carcinoma and no previous therapy. METHODS: PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 21 days. Pharmacokinetic studies to determine PZA plasma concentrations were performed. RESULTS: No responses were seen in 14 response-evaluable patients. Patients received a median of two cycles of PZA (range 1-6). Toxicity included neutropenia and neurologic side-effects, which were > or = grade III in 73% and 14%, respectively. High plasma concentrations of PZA (Cmax) correlated with low neutrophil counts (P = 0.04). CONCLUSIONS: PZA is inactive at this dose and schedule in colorectal cancer, and produces moderately severe toxicity.

Acridines↗
PubMed2000

Phase II trial of liposomal doxorubicin (Doxil) in advanced soft tissue sarcomas.

PURPOSE: To assess the objective response rate, toxicity experienced, progression-free survival, and overall survival of patients with previously untreated advanced soft tissue sarcomas treated with a liposomal doxorubicin formulation (Doxil). METHODS: Patients with metastatic or recurrent soft tissue sarcoma who had received no prior chemotherapy for advanced disease were treated with liposomal doxorubicin (Doxil) according to a two stage accrual design. Doxil was administered at 50 mg/m2 every 4 weeks. A total of 15 patients were treated and are evaluable for response and toxicity. RESULTS: The male/female ratio was 7/8, the median age was 60 years (34-75) and the ECOG performance status was 0-1 in >90% of patients. Leiomyosarcoma (7/15) and malignant fibrous histiocytoma (2/15) were the most common histologic diagnoses. No objective responses were observed in the 15 evaluable patients. No lethal toxicity occurred. Grade 3-4 leukopenia or neutropenia were reported in 3/15 (20%) patients. Grade 3 mucositis or hand-foot syndrome occurred in 2/15 (13%) and 1/15 (7%) patients respectively and seemed more severe in older patients. The median time to progression was 1.9 months (range 0.9-6.2). Twelve patients have now died. The Kaplan-Meier estimate of median overall survival is 12.3 months. As called for in the study design, accrual was terminated because no responses were obtained in the first 15 patients. CONCLUSION: Though well-tolerated, Doxil given according to this dose and schedule to patients with advanced soft tissue sarcoma had no significant therapeutic activity. A correlation between older age and skin/mucosal toxicity of Doxil is suggested in this study but needs confirmation. Future investigations of Doxil in soft tissue sarcomas should use a different schedule and dose.

Adult↗
PubMed1997

Randomized trial of carboplatin plus amifostine versus carboplatin alone in patients with advanced solid tumors.

BACKGROUND: To test the hypothesis that the cytoprotectant amifostine attenuates the thrombocytopenia produced by carboplatin, the authors performed a randomized trial comparing treatment with carboplatin alone versus the combination of amifostine and carboplatin. METHODS: Patients with refractory or carboplatin-sensitive malignancies were randomized to receive either carboplatin, 500 mg/m2 alone or carboplatin, 500 mg/m2 in conjunction with 2 doses of amifostine of 910 mg/m2 each. RESULTS: Fifty-five patients with a variety of malignancies were entered on this study. One patient withdrew from each arm prior to the administration of any therapy, leaving 30 evaluable patients treated with carboplatin alone and 23 treated with the combination of amifostine and carboplatin. For 82 cycles of therapy with amifostine plus carboplatin, the median platelet nadir was 127 x 10(9)/L while the median platelet nadir was 88 x 10(9)/L over the 80 courses of therapy with carboplatin alone (P = 0.023). The median platelet nadir after the first cycle of therapy was 144 x 10(9)/L for patients treated with amifostine plus carboplatin and 85 x 10(9)/L for patients treated with carboplatin alone (P = 0.24). The median survival for 9 patients with advanced nonsmall cell lung carcinoma treated with carboplatin alone was 39 weeks whereas the median survival for 12 such patients treated with amifostine plus carboplatin was 52 weeks (P = 0.116). CONCLUSIONS: These data support the hypothesis that amifostine attenuates the myelosuppression of carboplatin. Additional studies of amifostine in combination with carboplatin-containing chemotherapy regimens are warranted.

Adult↗
PubMed1994

Amifostine: potential for clinically useful cytoprotection.

The ability to target malignant cells for cytotoxicity while sparing normal host tissues has proven to be limited. These limitations have resulted in unacceptable toxicity or insufficiently effective therapy. Continuing investigation of new, potentially useful cytotoxic agents must continue. An alternative approach, also worthy of study, is the selective protection of normal tissues. This approach, used in conjunction with available therapeutic agents, may open the therapeutic window and incrementally enhance the effectiveness of cytotoxic therapy. A variety of methods have been used to protect normal tissues selectively. Regional protection can be used for certain organ systems, such as the oral mucosa. Selective protection on a systemic level is more difficult but agents that seem to protect normal but not malignant tissues selectively are being developed. Among these is amifostine, which was originally selected by the U.S. defense department for study as a radioprotectant. Pre-clinical studies have suggested that amifostine is differentially concentrated in normal tissues but not in malignant tissues. Tissue-specific differences in the activity of alkaline phosphatase, which dephosphorylates amifostine to its active metabolite WR-1065, and in pH are thought to be involved in this relative specificity. Clinical studies indicate that amifostine can reduce the myelosuppression produced by cyclosphosphamide, the combination of cyclophosphamide and cisplatin, and, perhaps, carboplatin. The protective effects of amifostine on nonhematopoietic toxicities are being investigated. Future trials will investigate the integration of amifostine with cytokine-based supportive care in order to define the role of this potentially clinically useful cytoprotectant agent.

Amifostine↗
PubMed1985

Eradication of neuroblastoma cells in vitro by monoclonal antibody and human complement: method for purging autologous bone marrow.

We describe an in vitro method which is useful for purging autologous bone marrow of neuroblastoma cells. The method utilizes a single murine monoclonal antibody 3G6 (an immunoglobulin MK) which we have previously developed against the ganglioside GD2; undiluted human complement; and unfractionated whole bone marrow at 1 X 10(7) nucleated cells/ml. Tumor cell clonogenic assays, Hoechst 33342 fluorescent nuclear stain, and trypan blue viability stain methods were used to assay cytotoxicity. This complement-mediated cytotoxicity technique killed 99.9-100% of neuroblastoma cell lines NMB-7, LAN-1, LAN-5, and IMR-6, while normal marrow precursor cells were not detectably damaged. The presence of normal bone marrow did not inhibit the human complement-mediated cytotoxicity. Applying the cytotoxicity method to whole unseparated bone marrow demonstrated killing of seeded neuroblastoma cells, with no gross hemolysis or cell clumping. The method did not require expensive special equipment, use of animal complement sera, or prior fractionation of the bone marrow. The average marrow nucleated cell recovery was 95%. These studies indicate that in vitro purging of autologous marrow infiltrated with neuroblastoma with monoclonal antibody 3G6 and human complement is both technically feasible and effective in eradicating residual tumor while preserving bone marrow stem cells.

Animals↗
PubMed1976

Fluorimetric studies of tryptophyl exposure in concanavalin A.

Studies of the iodide ion quenching of the intrinsic fluorescence of Concanavalin A indicate that 50% of the tryptophyl fluorescence originates from exposed residues. This agrees with the X-ray crystallographic determination that two of the four tryptophan residues in a Concanavalin A monomer are on the surface. Previous studies have indicated that conformational changes induced by sugar binding alter the environment of aromatic residues. The present investigation finds that neither the specific binding of alpha-methyl-D-mannoside nor alteration of the Concanavalin A quaternary structure changes the number or accessibility of the solvent-exposed tryptophan residues. It therefore appears that the major conformational transitions in Concanavalin A do not affect steric access to the surface tryptophans and the effects previously observed may be ascribed to structurally internal tryptophan residues.

Binding Sites↗