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PubMed1980

Effect of bleomycin, neocarzinostatin, and hydroxyurea on the preformed carrageenin granuloma in rats: mechanism of hyaluronic acid accumulation by bleomycin.

In order to elucidate whether the effects of bleomycin on the production or accumulation of intercellular substances by rat carrageenin granuloma are specific to bleomycin or a general response of the granulomatous tissue to the substances interfering with DNA synthesis, we examined the wet (or dry) weight and various components (DNA and glycosaminoglycans) in the granulomatous tissue of rats treated with bleomycin, neocarzinostatin, or hydroxyurea. The changes in various parameters of the granuloma after withdrawal of the inhibitors of DNA synthesis were different with different inhibitors tested. The highest recovery rate of DNA contents in the granulomatous tissue observed after withdrawal of bleomycin. It was also found that bleomycin caused much higher accumulation of hyaluronic acid in rat carrageenin granuloma than neocarzinostatin or hydroxyurea. This accumulation mechanism was indicated to be the results of the inhibition of mucopolysaccharidase activities via cells rather than those of the stimulation of glycosaminoglycan synthesis. These findings obtained in our experimental granuloma-system are of particular importance in considering the mechanism of the side effects of bleomycin.

Animals↗

PubMed2002

N-substituted hydroxyureas as urease inhibitors.

In order to seek a urease inhibitor more potent than hydroxyurea (1), its alkyl- or phenyl-substituted derivatives were synthesized and evaluated for their effect on the jack bean urease. Of 16 compounds tested, m-methyl- (10) and m-methoxy-phenyl substituted hydroxyurea (13) showed the most potent inhibitory activities against the enzyme.

Chemical Phenomena↗

PubMed2000

Oral ulcers caused by hydroxyurea.

We present a case of oral ulceration in a patient with essential thrombocythaemia, that proved to be secondary to treatment with hydroxyurea. This complication has not yet been reported in the ENT literature. Hydroxyurea should be considered as a possible cause of persistent oral ulceration in patients with haematological conditions. It should be noted that the onset of this complication is not related to the dose and duration of therapy.

Aged↗

PubMed1997

Minimal doses of hydroxyurea for sickle cell disease.

The use of hydroxyurea (HU) can improve the clinical course of sickle cell disease. However, several features of HU treatment remain unclear, including the predictability of drug response and determination of adequate doses, considering positive responses and minimal side effects. In order to identify adequate doses of HU for treatment of sickle cell disease, 10 patients, 8 with sickle cell anemia and 2 with S beta thalassemia (8SS, 2S beta), were studied for a period of 6 to 19 months in an open label dose escalation trial (10 to 20 mg kg-1 day-1). Hemoglobin (Hb), fetal hemoglobin (Hb F) and mean corpuscular volume (MCV) values and reticulocyte, neutrophil and platelet counts were performed every two weeks during the increase of the HU dose and every 4 weeks when the maximum HU dose was established. Reduction in the number of vasoocclusive episodes was also considered in order to evaluate the efficiency of the treatment. The final Hb and Hb F concentrations, and MCV values were significantly higher than the initial values, while the final reticulocyte and neutrophil counts were significantly lower. There was an improvement in the concentration of Hb (range: 0.7-2.0 g/dl) at 15 mg HU kg-1 day-1, but this concentration did not increase significantly when the HU dose was raised to 20 mg kg-1 day-1. The concentration of Hb F increased significantly (range: 1.0-18.1%) when 15 mg HU was used, and continued to increase when the dose was raised to 20 mg kg-1 day-1. The final MCV values increased 11-28 fl (femtoliters). However, reticulocyte (range: 51-205 x 10(9)/l) and neutrophil counts (range: 9.5-1.3 x 10(9)/l) obtained at this dose were significantly lower than those obtained with 15 mg kg-1 day-1. All patients reported a decrease in frequency or severity of vasoocclusive episodes. These results suggest that a hydroxyurea dose of 15 mg kg-1 day-1 seems to be adequate for treatment of sickle cell disease in view of the minimal side effects observed and the improvement in laboratory and clinical parameters.

Adolescent↗

PubMed1999

Hydroxyurea to inhibit human immunodeficiency virus-1 replication.

Treatment of human immunodeficiency virus (HIV) infection continues to be a challenge. Drug regimens that include two nucleoside reverse transcriptase inhibitors and a protease inhibitor are now the standard of care. These regimens require strict patient adherence and have numerous adverse effects at a high cost, so clinicians must continue to explore other therapeutic options. Hydroxyurea is a ribonucleotide reductase inhibitor that may have efficacy against HIV. We conducted a critical review of the literature to examine the utility of hydroxyurea-based drug combinations.

Anti-HIV Agents↗

PubMed2003

Intensive concurrent chemoradiotherapy for head and neck cancer with 5-Fluorouracil- and hydroxyurea-based regimens: reversing a pattern of failure.

Combined modality programs that were developed over the past two decades demonstrated that the nonsurgical therapy of locoregionally advanced head and neck cancer is feasible and produces survival outcomes that are at least comparable with surgery. The systemic therapy of head and neck cancer has gained momentum in recent years. Several randomized studies have shown that the concurrent administration of chemotherapy and radiation therapy is superior to radiation therapy alone. In consecutive clinical studies since 1986, we have developed multiagent chemoradiotherapy regimens based on initial observations with the 5-fluorouracil (5-FU), hydroxyurea, and concomitant radiotherapy combination. Three consecutive multicenter phase II trials reported that the combination of 5-FU and hydroxyurea with either cisplatin or paclitaxel along with twice daily radiation therapy administered every other week is a highly effective regimen with local control rates that approach 90% and 3-year survival rates of approximately 60% in patients with stage IV disease. The vast majority of patients in these studies achieved anatomical organ preservation. A reversal of the historical pattern of failure was evident, with distant sites becoming the predominant site of failure in each trial. The paclitaxel-containing regimen was better tolerated than the cisplatin-containing regimen and was advanced to further clinical testing. The incorporation of induction chemotherapy may improve the results of treatment by targeting systemic micrometastatic disease.

Aged↗

PubMed1997

Clinical and hematological response to hydroxyurea in a patient with Hb Lepore/beta-thalassemia.

The possibility of increasing Hb F in vivo using drugs like 5-azacytidine, hydroxyurea, and butyrate has been established. However, in many cases this does not entail an increase in total hemoglobin. We report on a patient with Hb Lepore/beta-thalassemia being treated with hydroxyurea (30 mg/Kg/day) because of the presence of erythroid extramedullary masses with severe neurological abnormalities. During therapy the patient showed a remarkable improvement in neurological signs due to the reduction in extra-medullary masses, a significant increase in both total hemoglobin (from 5.8 to 9.7 g/dl) and Hb F (from 4.9 g/dl to 9.1 g/dl). The marked improvement in hemoglobin level in our patient with Hb Lepore/beta-thalassemia suggests gamma-globin gene activation due to the DNA structure determined by the crossover event.

Adult↗

PubMed1997

Mobilisation and reinfusion of Philadelphia negative peripheral blood mononuclear cells in chronic myeloid leukaemia with hydroxyurea and G-CSF.

Unmanipulated autologous transplantation of marrow of peripheral blood stem cells has been performed in small numbers of patients with CML for many years. More recently there has been interest in attempting to 'purge' the autograft of clonal cells as defined by the presence of the Philadelphia chromosome or BCR-ABL rearrangement. One method by which this might be achieved in vivo has been developed in Genoa and involves the administration of high dose chemotherapy and G-CSF followed by peripheral blood stem cell collection. These collections are frequently devoid of Philadelphia positive cells and the hope is that this will enhance the effects of subsequent autograft. We have investigated the use of a less toxic regimen for this procedure using oral hydroxyurea and G-CSF. In this review we describe the background to autografting in CML and the development of strategies to mobilise Philadelphia negative cells into the peripheral blood. We go on to present an update of our data using hydroxyurea and discuss some of the practical and theoretical issues behind the procedure.

Adult↗

PubMed1999

Cutaneous ulcers associated with hydroxyurea therapy in myeloproliferative disorders.

Hydroxyurea (HU) is an established chemotherapeutic agent in the treatment of myeloproliferative disorders (MPD) including chronic myelogenous leukemia (CML), polycythemia vera and essential thrombocythemia (ET). It is well tolerated, has minimal toxicities, and produces hematological response in most patients treated. Side effects of hydroxyurea are few and include myelosuppression, oral ulcers and skin rashes. Cutaneous toxicity is rare. This study aims to describe the occurrence of cutaneous ulcerations attributed to HU therapy in patients with MPD, and familiarize the oncology community with this unusual but disturbing toxicity of HU. Five patients with MPD receiving HU therapy at doses of 0.5 to 4 g/day who developed skin ulceration were reviewed (median age was 53 years). Three patients had Philadelphia positive CML, and two had ET. Cutaneous ulcers developed after a long period of HU therapy (median 36 months, range 7 to 96 months). The time after discontinuation of HU to the healing of the ulcers was 1 to 4 months. Ulcers developed mainly in the lower extremities particularly adjacent to the malleoli, indicating a possible relation to trauma. In conclusion, cutaneous ulceration represents a poorly recognized and rare HU-related side effect. Discontinuation of HU usually leads to slow resolution of the ulcers over several months. The etiology of this rare side effect remains poorly understood.

Adult↗

PubMed1988

Treatment of medulloblastoma with procarbazine, hydroxyurea, and reduced radiation doses to whole brain and spine.

Forty-seven patients with medulloblastoma were treated postoperatively with procarbazine, followed by craniospinal radiation therapy in combination with hydroxyurea. The radiation dose to the posterior fossa was 55 Gy; the spinal cord received 25 Gy and the whole brain 25 to 35 Gy (mean 33 Gy). Seventeen tumors recurred. Only one initial recurrence was in the spinal subarachnoid space; 10 (59%) were in the posterior fossa, and four (24%) were supratentorial. The estimated 5-year disease-free survival probability was 55%; the 5-year overall survival rate was 66%. Myelotoxicity occurred in 38% of patients, but in only one case was it severe enough to warrant reducing the total dose of radiation. It was concluded that good-risk medulloblastoma patients may be treated with radiation dosages as low as 25 Gy to the spinal axis and to the whole brain without increasing the risk of recurrence outside the posterior fossa. Chemotherapy with procarbazine followed by radiation therapy and hydroxyurea during radiation therapy was well tolerated and may play a role in reducing radiation dosages outside the posterior fossa.

Adolescent↗

PubMedDate not supplied

Polycythemia vera in a cat and management with hydroxyurea.

Polycythemia vera (PV) was diagnosed in a four-year-old domestic shorthair evaluated for hind-limb ataxia, extension of all claws, and difficulty in jumping to elevated surfaces. Mild cardiac hypertrophy also was diagnosed. Initial laboratory evaluation revealed polycythemia (packed cell volume [PCV], 75%) and normal serum total protein (7.5 g/dl). Definitive diagnosis of PV was reached by excluding causes of relative and secondary absolute polycythemia using radiography, ultrasonography, and blood gases, and by measuring serum erythropoietin concentration by radioimmunoassay (13 mU/ml) and an enzyme-linked immunosorbent assay (ELISA) method (8.0 mU/ml). Bone-marrow biopsy revealed relative erythroid hyperplasia characteristic of myeloproliferative disease. Clinical signs were controlled with hydroxyurea (12.2 mg/kg body weight) and occasional phlebotomy. Polycythemia vera is an uncommon feline disease, and clinical reports on the use of hydroxyurea to manage the condition in the cat are lacking.

Animals↗

PubMed1980

Hydroxyurea induced hepatitis.

A case of hydroxyurea-induced self-limited hepatitis with an influenza-like reaction to hydroxyurea therapy is presented. The association was supported by recurrence of the symptoms on rechallenge with the drug.

Chemical and Drug Induced Liver Injury↗

PubMed1976

[Synchronization of cellular proliferation in mice with sarcoma 37 by using hydroxyurea].

The synchronizing effect of hydroxyurea on the passage of sarcoma 37 cells through the stage of the S-phase and mitosis was investigated in albino mice. The study was performed with consideration to the circadian variations in the mitotic activity and the labelled nuclei indices. The degree of synchronization was assessed by the changes in the cell count and the rate of changes in synchronicity. The tumour consisted of at least two cell populations in which the variations in the number of cells both at the S-period, and, possibly, in mitosis were shifted in respect to one another by phase. The rate of artificial cell synchronization in the mitosis proved to be much greater than the natural one in the tumour undivided into individual populations. However, the number of cells subjected to artificial synchronization showed no significant difference not only from the cell count in the tumour undivided into individual populations, but also from the number of cells synchronized naturally in one of the populations. This could be explained by the fact that hydroxyurea acted on one group of cells only since variations in the number of DNA-synthesizing cells were shifted in individual populations in respect to one another by phase.

Animals↗

PubMed1999

Use of hydroxyurea in psoriasis.

Hydroxyurea is an effective treatment in chronic plaque psoriasis that is relatively simple to prescribe. Dose-related bone marrow toxicity is the principal side-effect of therapy although clinically significant complications are few, provided that blood counts are monitored carefully. In contrast with many other second-line agents, renal and liver disease do not necessarily preclude treatment, and there are few drug interactions likely to be of clinical relevance in dermatology. Recent studies on the use of hydroxyurea for sickle cell disease may provide more information on predicting the maximal tolerated dose and potential hazards of long-term therapy in nonmalignant disease and perhaps revive interest in the drug's use in dermatology.

Humans↗

PubMed1975

Skin changes secondary to hydroxyurea therapy.

Hydroxyurea is an effective agent in the treatment of chronic myelogenous leukemia. The toxic reactions have included myelosuppression and megaloblastosis. During long-term maintenance therapy, dermatologic alterations occurred in seven of 20 patients and consisted of partial alopecia, increased pigmentation, scalings, atrophy of the skin and subcutaneous tissues, nail changes, and erythema of the face and hands. The histologic changes were similar to those seen in lichen planus. These observations were a factor leading to the use of hydroxyurea in the treatment of psoriasis.

Administration, Oral↗

PubMed1975

Hydroxyurea in the management of the hematologic complications of chronic granulocytic leukemia.

The effect of hydroxyurea in 35 patients with chronic granulocytic leukemia (CGL), who either had entered an accelerated phase of the disease or had experienced excessive myelosuppression following alkylating agents, was studied. By either intravenous or oral administration, the drug was successful in reducing peripheral leukocyte and blast counts in all cases and in reducing splenomegaly in 13 of 17 patients. The median duration of disease control was 75 days in myeloproliferative acceleration and 27 days in frank blastic transformation. Mild nausea and vomiting were experienced by most patients, but reversible bone marrow suppression occured in only three patients. The drug proved useful in 19 patients who demonstrated myeloproliferative acceleration, especially in controlling excessive leukocytosis and/or thrombocytosis. Rapid reduction of an elevated blast cell count was achieved in nine patients who presented in blastic crisis, in an attempt to eliminate the associated risk of cerebral vascular leukostasis. Five patients who required treatment for their disease following splenectomy in the chronic phase were also well controlled. Hydroxyurea appears to have a definite role in the management of these hematologic complications of CGL.

Busulfan↗

PubMed1997

[The effects of hydroxyurea on cell-cycle distribution and the expression of human beta-globin gene in K 562 cells].

Although the hydroxyurea (HU) has been extensively studied, little is known of its molecular mechanism in controlling the expression of human globin gene and in modulating the progression of cell-cycle in K 562 cell. In the present study, the effect of hydroxyurea on proliferative kinetics of K 562 cells was examined by monitoring the number of cells during a period of 8 day's cell culture. Our results showed that there was a dose related decrease in cell growth when K562 cells were incubated with HU. Moreover, cell-cycle analysis demonstrated that HU had profound effect on cell-cycle distribution. In the case of the induced K 562 cells, there was an increased accumulation of cells in S phase and a decreased fraction of cells in G 1 and G 2 + M phase. Furthermore, HU could induce the expression of human beta-globin gene in the induced K 562 cells. Our results indicate that HU has a potential to inhibit the proliferation of K 562 cells and to stimulate the terminal differentiation of this cell.

Cell Cycle↗

PubMed1976

Relationship of colony-stimulating activity to apparent kill of human colony-forming cells by irradiation and hydroxyurea.

Suspensions of human bone marrow cells were subjected to 137Cs irradiation in vitro and then cultured in semisolid agar medium. Cultures of irradiated cells were stimulated with colony-stimulating activity (CSA) of different potencies, and it was found that the amount of stimulation applied to cultures influenced the apparent kill of colony-forming cells (CFC). It was also found that the effects of irradiation on colony formation were not confined to CFC kill since medium conditioned by cells during irradiation exhibited stimulatory and inhibitory properties after treatment by 600 and 1000 rads, respectively. Studies in which irradiated cells were pretreated with hydroxyurea indicated that CFC in the DNA synthetic phase of the cell cycle were particularly sensitive to low doses of irradiation. The proliferative capacity of CFC surviving 1000 rads was undiminished as judged by their ability to form large colonies. Estimates of CFC kill by hydroxyurea were also affected by the level of CSA.

Bone Marrow↗