Randomized trial comparing the tolerability of sargramostim (yeast-derived RhuGM-CSF) and filgrastim (bacteria-derived RhuG-CSF) in cancer patients receiving myelosuppressive chemotherapy.

A prospective, randomized, double-blind, multicenter study in cancer patients receiving myelosuppressive chemotherapy was undertaken to evaluate and compare the tolerability of sargramostim (yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor, RhuGM-CSF) and filgrastim (bacteria-derived recombinant human granulocyte colony-stimulating factor, RhuG-CSF) in the prophylaxis or treatment of chemotherapy-induced neutropenia. In all, 137 evaluable patients received sargramostim (300 micrograms; 193 mg/m2) or filgrastim (481 mg; 7 mg/kg) once daily by self-administered s.c. injection, usually beginning within 48 h after completion of chemotherapy. With the exception of a slightly higher incidence of grade 1 fever (< 38.1 degrees C) with sargramostim, there were no statistically significant differences in the incidence or severity of local or systemic adverse events possibly related to the growth factors. Although the study was not designed to evaluate efficacy directly, there also were no statistically significant differences between treatment groups in total days of growth factor therapy, days of hospitalization, or days of i.v. antibiotic therapy during the treatment period. Both sargramostim and filgrastim were comparably well tolerated when given by s.c. injection in this group of patients, and no clinically significant differences between the growth factors were demonstrated.

Practical approaches to the management of aggressive lymphomas in the community practice.

Because of the variety of pathologic classifications for non-Hodgkin's lymphomas, it became necessary to develop a new system that incorporated the biologic, immunologic, and morphologic characteristics of these lymphomas. The National Cancer Institute (NCI) developed the Working Formulation that now classifies lymphomas into low, intermediate, and high grade. Physicians should be aware of these changes so that they can communicate with expert pathologists who speak the same language. Staging procedures to evaluate non-Hodgkin's lymphoma are similar to those used to evaluate Hodgkin's disease. The major advance in the treatment of this condition in the past few years has been in diffuse large cell lymphoma. Primary treatment programs using first-generation chemotherapy include CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), which is easy to administer and has a high complete remission (CR) rate of 51% and a 2-year survival of 39%. CHOP is about equal in activity to other first-generation regimens and remains the most frequent regimen to treat diffuse large cell lymphomas. Second-generation regimens were devised to increase the remission rate. COP-BLAM (cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, procarbazine), M-BACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone), and ProMACE-MOPP (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, procarbazine, prednisone) have produced CRs in excess of 70% and have demonstrated an increase in survival that has been associated with a concomitant increase in toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical considerations of hormonal receptors in breast cancer.

PIP: Focus is on the current concepts of hormone receptors in breast cancer and their significance to the practicing physician. Hormone receptor assays have proven to be valuable to physicians treating patients with breast cancer. About 2/3 of patients with estrogen receptor (ER+) tumors experience palliation of their symptoms after some type of hormonal manipulation. At this time it is believed that estrogen exerts the most powerful effect on the cancer. There are several methods of testing for estrogen receptors. The 1st method involves injection of tritiated hexesterol prior to surgery and subsequent checking for radioactive estrogens in the mammary tissue. More recently, methods are used in which the receptors can be quantified. 1 method uses a sucrose density gradient. Another and less expensive method is the Dextran-coated charcoal test (DCC). Estrogen receptors have been found in 73% of primary and 58% of metastatic breast cancers using the DCC test. The treatment of choice is always dependent on the patient involved. If the lesion is ER+, some type of hormone manipulation may be considered, which type depending on the menopausal status of the women.^ieng

Immunosuppressive and cytotoxic chemotherapy: long-term complications.

PIP: Cytotoxic drugs, which are widely used as immunosuppressive and antiinflammatory agents in patients with neoplastic conditions, and cancer chemotherapy preparations, are of long-range concern due to the problem of cumulative organ toxicity which is not manifested until damage is extensive. These considerations have arisen because of their widespread use in recent years. Those involved in hepatic toxicity are the antimetabolites methotrexate and 6-mercaptopurine. Bisulfin, bleomycin, and methotrexate have been linked to pulmonary toxicity. Daunomycin and adriamycin, used as anticarcinogens, are examined for their cardiac toxicity. Cyclophosphamide and streptozotocin affect the urinary tract. These drugs have specific toxic effects on fertility in both males, through its disruption of the testicular function, and in females, for ovarian disruptions. Antifolics, 6-mercaptopurine, azathioprine, and alkylating agents, used for therapy in pregnant women, particularly in the first 4 months, are linked to the appearance of fetal abnormalities. The process of carcinogenesis is examined for clues to possible chemotherapy-related 2nd tumors, which appear during the course of treatment.^ieng