Pincer complexes of the type [2,6-(R(2)PO)(2)C(6)H(3)]NiSC(6)H(4)Z (R = Ph and i-Pr; Z = p-OCH(3), p-CH(3), H, p-Cl, and p-CF(3)) have been synthesized from [2,6-(R(2)PO)(2)C(6)H(3)]NiCl and sodium arylthiolate. X-ray structure determinations of these thiolate complexes have shown a somewhat constant Ni-S bond length (approx. 2.20 Å) but an almost unpredictable orientation of the thiolate ligand. Equilibrium constants for various thiolate exchange (between a nickel thiolate complex and a free thiol, or between two different nickel thiolate complexes) reactions have been measured. Evidently, the thiolate ligand with an electron-withdrawing substituent prefers to bond with "[2,6-(Ph(2)PO)(2)C(6)H(3)]Ni" rather than "[2,6-(i-Pr(2)PO)(2)C(6)H(3)]Ni", and bonds least favourably with hydrogen. The reactions of the thiolate complexes with halogenated compounds such as PhCH(2)Br, CH(3)I, CCl(4), and Ph(3)CCl have been examined and several mechanistic pathways have been explored.

Rituximab (Rituxan) was the first monoclonal antibody approved for cancer therapy and the first single-agent approved for therapy of lymphoma. When combined with CHOP, rituximab is the only drug that has been shown to improve survival of a subpopulation of patients with diffuse large cell lymphoma during the last three decades. It was approved by the FDA for the treatment of patients with relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma in 1997. Rituximab is also being studied in many other B-cell malignancies alone and in combination with other agents. Furthermore, it is currently being evaluated in several nonmalignant diseases, such as autoimmune disorders. This review will focus on the role of rituximab in patients with non-Hodgkin's lymphoma.

PURPOSE: Methotrexate (MTX) is active against lymphomas, but transport or polyglutamylation mutations confer MTX resistance. Because trimetrexate (TMTX) enters cells by passive diffusion and is not polyglutamylated, its activity in relapsed T-cell lymphoma was investigated. PATIENTS AND METHODS: Eligible patients had histologically confirmed relapsed T-cell lymphoma involving the skin, had received more than one previous regimen, were older than 16 years, had normal organ function, and had no CNS disease or serious infections, including human immunodeficiency virus. TMTX (200 mg/m2) was given intravenously every 14 days without topical or systemic corticosteroids. Patients who responded received up to 12 doses. RESULTS: Twenty patients were assessable for response. Median age was 59 years (range, 45 to 87 years); 13 patients were men. Three patients had anaplastic large-cell lymphoma, 15 had mycosis fungoides or Sézary syndrome (14 with large-cell transformation), and two had peripheral T-cell lymphoma. Serum lactate dehydrogenase was high in 35%, and beta-2 microglobulin was more than 3.0 mg/L in 35% of patients. The median number of previous regimens was three (range, two to 15) and included MTX in five patients. Disease was refractory to the regimen immediately preceding TMTX in 85% of patients. Responses were complete in one and partial in eight patients (overall response rate, 45%). Two of five patients previously treated with MTX responded. Grade 3 or 4 mucositis was observed after 4%, infection after 3%, neutropenic fever after 6%, neutrophils less than 100/μL after 4%, and platelets less than 10,000/μL after 3% of TMTX doses. CONCLUSION: TMTX is active with acceptable toxicity in this population and merits further investigation.

Intrathecal administration of methotrexate sodium and cytarabine with or without hydrocortisone sodium succinate is commonly used to treat metastatic spread of malignancies to the leptomeninges. The existing stability information on these drug combinations is inadequate due to the clinical use of increased doses of the drugs, as well as a change in the formulation of Elliott’s B Solution. The purpose of this study was to evaluate the physical and chemical stability of simulated high intrathecal doses of the subject drugs in the current formulation of Elliott’s B Solution. Methotrexate sodium 6, 12, and 15 mg was combined with cytarabine 100 mg with and without hydrocortisone sodium succinate 100 mg using Elliott’s B Solution as the intrathecal vehicle. Samples were stored at 4 and 23°C and evaluated for physical and chemical stability over 48 h. No precipitation or other evidence of physical instability was observed in any sample. Measured pH was 7.2- 7.5 in the samples and was sufficient to prevent methotrexate precipitation. High-performance liquid chromatography analysis found little or no loss of methotrexate and cytarabine in any sample and hydrocortisone at 4°C. At room temperature, hydrocortisone losses of 6-8% occurred in 48 h. The high doses of methotrexate sodium and cytarabine with or without hydrocortisone sodium succinate evaluated in this study are physically and chemically stable for 48 h at 4 and 23°C in Elliott’s B Solution.

Healthcare costs in the USA continue to rise faster than the consumer price index. Nothing demonstrates this more vividly than the double-digit increases posted for the cost of the drug treatment of the oncology patient. A factor that will compound this cost is the expansion in the oncology patient population that will occur as the population ages. Pharmacoeconomics is a discipline that evaluates the relationship between clinical, economic and humanistic outcomes to determine the products and services that maximize the value for each dollar spent. Research in this area is evolving to meet the needs of the individual patient and decision-makers within a payer group, healthcare system, or society. Healthcare interests in countries in Europe, Canada and Australia have already adopted analytical tools and incorporated them into guidelines for drug use. The USA is also moving in this direction now that the Food and Drug Administration is considering requiring studies in pharmacoeconomics in addition to the standard studies of the safety and efficacy of drugs. The importance of this approach to oncology will be seen as policy-makers apply research findings to practice decisions.