Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since July 1984, eight patients with advanced hairy cell leukemia have received treatment with recombinant alpha A interferon. At commencement of interferon, seven patients had progressive cytopenia, and one was in leukemic phase (greater than 20 x 10(9)/L circulating hairy cells). All patients had had previous splenectomy. Interferon was administered subcutaneously. The initial dose was 3 x 10(6) U/day, continued until peripheral counts stabilised. Subsequently, patients received 6 x 10(6) U/day, 9 x 10(6) U/day, and finally 12 x 10(6) U/day. The dose increases proceeded every 8-12 weeks, as tolerated. Seven patients had an objective response. There were four complete remissions, two partial remissions, and one minor response. Complete remission was documented only in patients on at least 6 x 10(6) U/day for 12 weeks. The median time to complete remission was 40 weeks (range 35-53). Normalisation of peripheral blood counts preceded histologic marrow improvement. The median times for response (platelets greater than or equal to 100 x 10(9)/L, hemaglobin greater than or equal to 12 gm/dL, neutrophils greater than or equal to 1.5 x 10(9)/L), were six to eight and 17 weeks, respectively. Toxicity included myelosuppression during the first four weeks of therapy. With increasing doses of interferon, myelosuppression did not recur. A transient, mild, flu-like syndrome affected all patients. Two patients developed asymptomatic transaminitis at doses greater than 6 X 10(6) U/day. This resolved with dose reduction. In one case impotence was reported during the first four weeks of each interferon level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of hairy cell leukemia with increasing doses of recombinant alpha A interferon. 319 42

Alpha-2-interferon (IFN) has demonstrable activity in advanced, relapsing, or refractory multiple myeloma. Because of the in vitro synergism between the IFNs and cytotoxic agents, we conducted a trial of 30 previously untreated patients with multiple myeloma utilizing various doses of alpha-2-IFN in combination with standard oral doses of melphalan and prednisone. The combination was well-tolerated without unusual or unexpected toxic effects. The limiting toxicity included dose-related myelosuppression, and alpha-2-IFN induced flu-like symptoms and fatigue. Response was seen in at least as many patients as would be expected with melphalan and prednisone alone. The maximal tolerated dose for a phase II-III trial was 5.0 X 10(6) IU/m2 of alpha-2-IFN in combination with standard doses of melphalan and prednisone. Future trials should utilize this dose of alpha-2-IFN with dose de-escalation according to tolerance.
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PMID:Alpha-2-interferon/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial. 369 41

Twenty previously treated patients with multiple myeloma were treated with rDNA human alpha-2 interferon (INTRON A) in a phase II trial. Patients received an induction phase of therapy consisting of 3-100 X 10(6) IU/m2 iv given every other day pending myelosuppression. Patients then received 10 X 10(6) IU/m2 three times a week sc. In patients not responding to the iv and sc protocol, prednisone (20 mg orally) was given with each dose of INTRON A to determine whether additional responses could be produced and whether toxicity could be reduced. During the sc phases of therapy, INTRON A was escalated pending hematologic and nonhematologic toxicity. Three partial remissions were achieved in patients receiving the initial iv/sc therapy, and one additional patient responded when prednisone was added (durations of remission, 5, 6, 8, and 9 months). Myelosuppression was the dose-limiting toxic effect in both the iv and sc phases of therapy. Constitutional symptoms (flu-like) were seen in the majority of patients, but were tolerable. With the utilization of prednisone, flu-like symptoms were reduced in frequency and degree. Escalation of the dose of INTRON A was possible in the majority of patients when prednisone was added; however, only one patient (of seven) responded to combination therapy. INTRON A can produce remissions in 20% of patients with previously treated multiple myeloma. No improvement in the response rate was achieved utilizing a high-dose induction program. Although the dose of INTRON A could be escalated when prednisone was added, the response rate was not enhanced.
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PMID:Phase II study of rDNA alpha-2 interferon (INTRON A) in patients with multiple myeloma utilizing an escalating induction phase. 376 70

Alpha interferons are biological response modifiers that regulate immune function, slow cell proliferation, and inhibit virus replication. Large supplies of purified preparations are now available for clinical trials. Common toxicity includes an influenza-like syndrome to which tolerance occurs after several doses, and chronic fatigue and anorexia that may be dose-limiting. Myelosuppression is mild. Alpha interferons have established clinical activity against several human cancers, including melanoma, Kaposi's sarcoma, multiple myeloma, non-Hodgkin's lymphoma, hairy cell leukemia, and renal cell carcinoma. These data and alpha interferon nomenclature are summarized in table form. Intranasal alpha interferon is effective in prophylaxis of common viral upper respiratory tract infections, although toxicity in long-term use is prohibitive. Short-term administration to high risk populations may be most useful. Optimal doses and schedules need to be determined for all indications.
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PMID:The new alpha interferons. 391 Mar 84

This study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.
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PMID:A phase I toxicity study of human rDNA interferon in patients with solid tumours. 646 93

Four patients with adult T-cell leukemia (ATL) and 4 patients with non-Hodgkin's lymphoma were treated with alpha-type interferon (Human Lymphoblastoid Interferon: HLBI). Treatment regimen consisted of 3 to 12 million units (MU) of HLBI given intramuscularly once daily. The total dose varied from 36 to 520 MU. Complete remissions were obtained in one of 4 patients with ATL and one of 3 patients with B-cell lymphoma. A partial remission was yielded in one patient with B-cell lymphoma. An overall response rate (CR + PR) was 37.5%. Toxicity included flu-like symptoms, myelosuppression, G-I tract symptoms, fatigue, high fever and hepatic disturbance. On the basis of this study, we have concluded that HLBI is effective for the treatment of ATL and B-cell lymphoma.
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PMID:[Effect of human lymphoblast interferon in adult T-cell leukemia and non-Hodgkin's lymphoma]. 660 14

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical toxicity of the interferons. 751 63

Fourteen patients with diffuse malignant pleural mesothelioma (DMPM) were enrolled in a Phase II study to assess activity and toxicity of the systemic administration of recombinant (r)-alpha-interferon (IFN)-2b. The IFN schedule was: 3 x 10(6) IU i.m. days 1-4, 6 x 10(6) IU days 5-8, 10 x 10(6) IU days 9-12; then IFN was administered at 10 x 10(6) IU 3 days/week. If grades II-III toxicity occurred, IFN dose was reduced and drug continued at the previous dose level. All patients were evaluated by CT scan. Only one patient was not evaluable for response and toxicity because of inadequate follow-up. Of 13 evaluable patients, we observed 1 objective response, 6 stable disease, and 6 failures (3 progressive disease and 3 early interruptions due to subjective toxicity). The median time to progression was 19 weeks, and the median overall survival was 62 weeks. Toxicity was mild: of 13 patients evaluable for toxicity we observed fever (9 patients), flu-like syndrome (3 patients), fatigue (4 patients), anorexia (2 patients), myelosuppression (3 patients), and muscle pain (1 patient). The results of this study indicate only marginal activity of r-alpha-IFN in the treatment of DMPM.
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PMID:Recombinant interferon alpha-2b in the treatment of diffuse malignant pleural mesothelioma. 831 Oct 14

Extensive data generated from early phase I trials have demonstrated important schedule-dependent differences in gemcitabine's toxicity profile and activity. Frequent drug administration produced a high incidence of toxicities: in the daily schedule, flu-like symptoms (fever, malaise, and headache) were experienced and in some patients idiosyncratic episodes of severe hypotension; in the twice-a-week schedule the dose-limiting toxicity was thrombocytopenia. Less frequent drug administration was better tolerated (dose-limiting toxicity was myelosuppression), but little efficacy was observed. These three schedules were not followed up in phase II studies. Instead, a weekly schedule was selected in which gemcitabine was given as a 30-minute infusion once a week for 3 weeks followed by a week of rest. In this schedule, gemcitabine provided a combination of activity and acceptable tolerability, with dose-limiting toxicity being thrombocytopenia at doses of 790 to 1,500 mg/m2. An understanding of the clinical pharmacology of this novel agent has resulted in a second generation of phase I trials that attempt to increase dose intensity, maintain an acceptable toxicity profile, and improve the efficacy in minimally pre-treated or untreated patients. Most of the studies used the weekly schedule of drug administration. Strategies include escalating dose and increasing infusion duration. At present, the gemcitabine dose with the best balance of activity and tolerability is weekly doses of 1,000 mg/m2 administered over 30 minutes. However, additional studies will be needed to explore completely the newer strategies for dose intensification described in this overview.
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PMID:Phase I studies with the novel nucleoside analog gemcitabine. 889 78

The novel nucleoside analog, gemcitabine, appears to be exceptionally well tolerated. To examine gemcitabine's toxicity profile in detail, an analysis of safety data from 18 single-agent gemcitabine studies has been performed. The studies were across a range of tumor types, but all used a dose regimen of 800 to 1,250 mg/ m2 once a week for 3 weeks followed by a week of rest. Seven hundred ninety patients were included in the analysis. Myelosuppression was found to be mild and short-lived: World Health Organization grades 3 and 4, respectively, were recorded in 6.4% and 0.9% of patients for hemoglobin, in 8.1% and 0.5% for leukocytes, in 18.7% and 5.7% for neutrophils, and in 3.7% and 1.0% for platelets. There was little associated infection or hemorrhage. Mild transaminase increases were common but were rarely dose limiting. In general, renal toxicity was mild, but a few cases of renal failure of uncertain etiology were reported. There was little symptomatic toxicity, with low incidences of the gastrointestinal and hair toxicities normally associated with cytotoxic drugs. However, there was a higher incidence than expected of flu-like symptoms and edema, although these were rarely serious. When the safety data from non-small cell lung cancer studies were analyzed separately, the toxicity findings were similar. Therefore, these analyses in large numbers of patients confirm gemcitabine's favorable safety profile.
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PMID:Gemcitabine safety overview. 889 79


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