Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because recombinant interleukin 2 (rIL-2) and recombinant alpha-interferon (rIFN-alpha) exhibit synergistic antitumor activity in C3HMT1820 T-cell lymphoma and B16 melanoma tumor systems, we have performed a Phase I study of this combination in 55 patients with advanced malignancies for whom no standard therapy exists. Successive groups of greater than or equal to 4 patients have been entered into 12 dose levels (1A-3D), with dose levels 1-3 referring to doses of rIL-2 of 0.1, 0.5, and 2.0 x 10(6) units/m2, respectively, and dose levels A-D referring to doses of recombinant human alpha 2a-interferon (rHuIFN-alpha 2a) of 0, 0.1, 1.0, and 10.0 x 10(6) units/m2. Both agents were given on Mondays, Wednesdays, and Fridays, with rIL-2 being given as i.v. bolus injections and rHuIFN-alpha 2a being given intramuscularly. Myelosuppression was dose-limiting and was related primarily to the dose of rHuIFN-alpha 2a. The maximum-tolerated dose level was reached at a dose of rIL-2 of 2.0 x 10(6) units/m2 and of rHuIFN-alpha 2a of 10.0 x 10(6) units/m2 (dose level 3D). At this dose level, 3/6 patients developed grade 3 neutropenia (absolute granulocyte count less than 1 x 10(9)/liter). Myelosuppression was transient, with no documented infections being associated with neutropenia. Hypotension was mild; a single patient was treated with a vasopressor, but all other cases of hypotension responded to fluid administration. No significant pulmonary toxicity was produced. Fever, chills, and malaise were universal but not dose-limiting. Three partial responses and one minor response were observed in patients with malignant melanoma, renal cell carcinoma, and breast cancer. Immunological studies suggested that natural killer activity was related to both the dose of rIL-2 and the dose of rHuIFN-alpha 2a, with natural killer activity being positively related to the dose of rIL-2 and maximal at the lowest dose of rHuIFN-alpha 2a of 0.1 x 10(6) units/m2.
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PMID:Phase I clinical trial of interleukin 2 and alpha-interferon: toxicity and immunologic effects. 280 86

Sixty cats with hematologic abnormalities indicative of non-lymphoid hematopoietic neoplasia were classified into two groups, myelodysplastic syndromes (MDS) and acute myelogenous leukemias (AML), using criteria developed for human patients with similar diseases. Cats with myeloblast counts in bone marrow of less than 30% were classed as MDS and cats with myeloblast counts of 30% or greater were classed as AML. The clinical, laboratory, and postmortem findings in each group were described and compared. Clinical signs of disease were similar in both groups, the most common being inappetance, lethargy, and weakness. Non-regenerative anemia, macrocytosis, neutropenia, and thrombocytopenia were frequent hemogram abnormalities in both groups. Diagnostically useful differences in physical and peripheral blood findings were a higher prevalence of splenomegaly and/or hepatomegaly, thrombocytopenia, and severe anemia in the AML group. Circulating myeloblasts were found only in cats in the AML group. Outcome of disease was similar in both groups; 85% of the cats in each group died or were euthanatized within one week of diagnosis. In cats that were necropsied, extramedullary leukemic infiltrates were found in all cats in the AML group and in none of the cats in the MDS group.
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PMID:Non-lymphoid hematopoietic neoplasia in cats: a retrospective study of 60 cases. 282 80

To assess the efficacy and safety of Adriamycin (Adria Laboratories, Columbus, OH) in inoperable hepatocellular carcinoma (HCC), 60 patients were randomized to receive Adriamycin 60 to 75 mg/m2 at 3-week intervals and 46 patients to receive no antitumor therapy. The median survival rate of the Adriamycin group was 10.6 weeks; that of the group receiving no antitumor therapy was 7.5 weeks (P = 0.036). Adriamycin induced tumor regression of 25% to 50% in 5% of patients and of over 50% in only 3.3% of patients. It caused fatal complications (septicemia and cardiotoxicity) in 25% of patients. The severity of neutropenia leading to septicemia for a particular dose was unpredictable. Four of eight patients who developed cardiotoxicity received less than 500 mg/m2 of Adriamycin. We conclude that Adriamycin is not an ideal drug for the treatment of inoperable HCC.
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PMID:Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial. 283 80

Two hundred sixty-three patients with advanced breast cancer were randomized to two treatment regimens consisting of fluorouracil, 500 mg/m2; cyclophosphamide, 500 mg/m2; and either epirubicin (Farmorubicin, Farmitalia Carlo Erba SpA, Italy), 50 mg/m2 (FEC); or doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), 50 mg/m2 (FAC), administered intravenously (IV) every 3 weeks. Two hundred thirty patients (FAC, 113; FEC, 117) were evaluable for response, and 244 patients for toxicity (FAC, 120; FEC, 124). The two groups were comparable with respect to age, menopausal status, disease-free interval to first recurrence, time from initial diagnosis to protocol activation, indicator lesions, performance status, and prior adjuvant therapy. Of 117 evaluable patients treated with FEC, 59 (50.4%) had a partial response (PR) or complete response (CR), 40 showed no change (NC), and 18 had progressive disease. Of 113 evaluable patients treated with FAC, 54 (52%) showed a remission, 30 NC, and 18 progression. There was no statistical difference between the two regimens in overall response rate, response rate according to tumor site, time to response, or duration of response. Median survival was 15 months for FEC and 18.2 months for FAC (not significant). In the 120 patients evaluable for toxicity treated with FAC, three episodes of congestive heart failure (CHF) were observed after 225, 350, and 550 mg/m2 of doxorubicin, respectively. Of the 124 evaluable patients treated with FEC, 25 received greater than 600 mg/m2 of epirubicin and no CHF was recorded. FEC induced significantly less neutropenia (P = .01), less nausea and vomiting (P less than .01), and less complete alopecia (P less than 10(-3) than did FAC. The results of this study demonstrate that FEC is as effective a regimen as FAC for the therapy of advanced breast cancer. Moreover, FEC was better tolerated than FAC in this patient population.
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PMID:A prospective randomized phase III trial comparing combination chemotherapy with cyclophosphamide, fluorouracil, and either doxorubicin or epirubicin. French Epirubicin Study Group. 289 1

Morphologically distinct lymphoid cells with homogeneous, condensed chromatin and scant cytoplasm can be observed in large numbers in the bone marrow of children with a variety of hematologic and nonhematologic disorders. In some patients, these cells may account for greater than 50% of the bone marrow cells, creating a picture that can be confused with acute lymphoblastic leukemia (ALL) or metastatic tumor. Although originally called hematogones (HGs), a variety of other names have been proposed for these unique cells. The clinical significance of expanded HGs has not been resolved, and the biologic features of these cells are incompletely described. In this study, we correlate the clinical, morphologic, cytochemical, flow cytometric, molecular, and cytogenetic properties of bone marrow samples from 12 children with substantial numbers of HGs (range 8% to 55% of bone marrow cells). Diagnoses in these patients included anemia, four; neutropenia, one; anemia and neutropenia, one; idiopathic thrombocytopenic purpura, two; retinoblastoma, two; Ewing's sarcoma, one; and germ cell tumor, one. Flow cytometric analyses of bone marrow cells demonstrated a spectrum extending from early B-cell precursors (CD10+, CD19+, TdT+, HLA-Dr+) to mature surface immunoglobulin-bearing B cells in these patients, corroborating our morphologic impression of HGs, intermediate forms, and mature lymphocytes. DNA content was normal, and no clonal abnormality was identified by either cytogenetic or immunoglobulin and T-cell receptor (TCR) gene rearrangement studies. Follow-up ranged from 3 months to 3 years. None of the patients has developed acute leukemia or bone marrow involvement by solid tumor. The possible role of HGs in immune recovery and hematopoiesis is presented.
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PMID:Hematogones: a multiparameter analysis of bone marrow precursor cells. 291 89

In this phase I study, we administered etoposide (VP-16) orally for 21 consecutive days to patients with advanced refractory cancers. All patients had received previous chemotherapy, and 50% of patients had received more than one combination regimen. When given for 21 consecutive days, the maximum-tolerated dose of oral VP-16 was 50 mg/m2/d. Myelosuppression was the dose-limiting toxicity, and occurred between days 21 and 28. In most patients, blood counts had recovered sufficiently by day 35 to begin another 3-week course. WBC count nadirs of less than 1,000/microL occurred in four of 20 courses at this dose, and three patients required hospitalization for treatment of neutropenia and fever. Alopecia occurred in most patients; gastrointestinal (GI) and other toxicities were uncommon. Five of 16 patients with measurable tumor had partial responses of 3 to 4 months duration. Four of these five patients had malignancies that are usually unresponsive to VP-16 when administered by previously investigated schedules. This method of VP-16 administration is well tolerated, convenient, and may optimize antitumor efficacy by exploiting the schedule dependency of this drug. Phase II studies are necessary to define the level of activity of this schedule of VP-16.
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PMID:Chronic daily administration of oral etoposide--a phase I trial. 291 34

Nasopharyngeal carcinoma (NPC) is a human neoplasm closely associated with Epstein-Barr virus (EBV). Human leukocyte interferon (IFN) has known antiviral and antineoplastic properties. After initial IFN treatment in one NPC patient demonstrated acceptably low toxicity, 12 additional patients were treated on a protocol with IFN, 10 X 10(6) units intramuscularly (IM) daily for 30 days. IFN did not affect serum anti-EBV antibody titers (IgA and IgG antiviral capsid and early antigens). Of six patients tested, none was found to excrete EBV in saliva before, during, or after IFN. Four patients had measurable tumor regression (two partial responses and two minor responses), three had stable disease, and five patients plus the initial preprotocol patient had progressive disease. Toxicity included fever, fatigue, and myalgias in all patients, thrombocytopenia in two patients, and neutropenia in three patients. Three patients were withdrawn from the study, one each for severe fatigue, neutropenia, and hypotension. This study demonstrates that IFN has sufficient activity in advanced NPC to justify further investigation.
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PMID:Treatment of nasopharyngeal carcinoma with human leukocyte interferon. 298 45

Nephrotoxicity of cisplatin can be ameliorated with intravenous (IV) hydration and forced diuresis with mannitol. Cisplatin has recently been used with hypertonic saline which allows administration of higher doses amounting to 40 mg/m2/d for 5 days, without significant nephrotoxicity. In this report we describe our experience with administration of cisplatin in a dose range of 30 to 40 mg/m2/d for 5 days, administered with IV hydration alone. Thirteen patients with recurrent carcinoma of the head and neck region were treated with high-dose cisplatin along with 5-fluorouracil (5-FU) used as a continuous infusion. Eight patients received a total of 21 courses of cisplatin with the higher dose range (40 mg/m2 for 5 days) and the remainder received 11 courses with the lower dose range. The renal toxicity was minimal but the myelo-suppression was intense, frequently requiring hospitalization for the treatment of infections associated with neutropenia. Furthermore, we encountered severe peripheral neuropathy in five patients, four of whom developed major difficulties with ambulation. Six patients achieved objective regression of their tumor, two had minor response, and five failed to respond to chemotherapy. The study was terminated because of serious nonrenal toxicity from the high-dose cisplatin. Based on our limited experience, we believe that IV hydration alone, without the use of hypertonic saline, allows administration of high-dose cisplatin without significant nephrotoxicity. However, cisplatin used in a dose schedule of 40 mg/m2 for 5 days for more than three courses resulted in a disabling form of peripheral neuropathy.
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PMID:High-dose cisplatin administration without hypertonic saline: observation of disabling neurotoxicity. 299

Treatment results remain very poor for some clinical and histopathologic subsets of patients with aggressive non-Hodgkin's lymphoma. We treated 21 such patients with a high-dose combination chemotherapy regimen [Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)] in an attempt to improve disease-free survival. Neoplasms were classified using the Lukes-Collins system. Eight patients had T-cell lymphomas (convoluted lymphocytic lymphoma, four patients; T-cell lymphoma/leukemia, one; and peripheral T-cell lymphoma, three), eight had B-cell lymphomas (immunoblastic sarcoma, five patients; small noncleaved follicular center cell, one; and large noncleaved follicular center cell, two), and five had nontypable large noncleaved cell lymphomas. All patients were previously untreated; 18 of 21 patients had clinical stage III or IV disease. Following induction therapy (4-8 weeks' duration), 16 patients (76%) achieved complete remission, while three had partial remission. Two patients died of sepsis during induction therapy. Eleven of 16 complete responders (69%) remain in complete remission after a median follow-up of 35 months. The actuarial 3-year survival rate is 51% for the entire group. Myelosuppression with this regimen was severe and prolonged, with a median duration of neutropenia (less than 500 cells/microliter) of 14 days. Seven patients (33%) developed severe neuropathy following induction treatment. High-dose induction therapy with this regimen resulted in a high complete remission rate with manageable toxicity. Survival results are encouraging when compared retrospectively to our patients with similar poor-prognosis histologies treated with standard combination chemotherapy. However, the value of this intensive therapy, relative to newer ("third-generation") regimens, can only be established by prospective randomized studies.
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PMID:Effects of Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in the treatment of lymphoid neoplasms with very poor prognosis. 301 6

In an attempt to circumvent innate or acquired tumor-cell resistance to chemotherapy, patients with small-cell lung cancer (SCLC) were treated with induction therapy that incorporated two active and potentially non-cross-resistant chemotherapy regimens on two National Cancer Institute of Canada (NCI-C) trials. Patients with limited disease (LD) SCLC were treated with cyclophosphamide, doxorubicin (Adriamycin [Adria Laboratories, Columbus, Ohio]) and vincristine (CAV) and VP-16 plus cisplatin in two different sequences. One arm was randomized to receive CAV alternating with VP-16 plus cisplatin for a total of six treatment cycles, and the other arm received three courses of CAV followed by three courses of VP-16 plus cisplatin. Both treatment strategies produced similar response rates and survival curves, and each treatment group has a projected 2-year survival of 20%. Patients with extensive disease (ED) were treated with either six cycles of CAV (standard regimen) or CAV alternating with VP-16 plus cisplatin for a total of six treatment cycles. In this study, the alternating regimen produced a higher complete response (CR) rate (40% v 27%) and overall response rate (61% v 39%; P less than .01). The progression-free survival was also superior for the alternating arm (P = .001), as was overall survival (P less than .05). The frequency of thrombocytopenia and severe gastrointestinal toxicity was slightly greater in the alternating arm, but the frequency of neutropenia and infection was less. The alternation of CAV and VP-16 plus cisplatin during induction therapy is an effective treatment strategy in the management of SCLC and superior to CAV alone in extensive SCLC.
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PMID:The use of VP-16 plus cisplatin during induction chemotherapy for small-cell lung cancer. 302 Jun 92


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