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)

During the phase I study of maytansine at our institution, some activity was observed against breast carcinoma and melanoma. A phase II study was thus initiated to more thoroughly investigate the activity of this drug against these two tumors. In 33 evaluable patients with melanoma, no complete or partial responses were observed. Twenty-one evaluable patients with breast cancer were entered and only one response (partial) was seen. The toxicity was similar to that observed in the phase I study and consisted mainly of diarrhea, paresthesias, phlebitis, and flu-like symptoms. Myelosuppression was infrequent and was short-lived when it occurred.
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PMID:Results of a phase II study of maytansine in patients with breast carcinoma and melanoma. 37 3

Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a polypeptide hormone produced through recombinant DNA technologies in glycosylated (yeast or mammalian expression systems) or nonglycosylated (Escherichia coli expression system) form. It is a multilineage haematopoietin which stimulates proliferation and differentiation of bone marrow myeloid progenitors and increases peripheral white blood cell counts when administered systemically. Treatment is generally well tolerated, although mild to moderate flu-like symptoms are common and rGM-CSF-induced fever and fluid retention may be problematic in occasional patients. rGM-CSF accelerates recovery of peripheral neutrophil counts after bone marrow transplantation, and results of a placebo-controlled randomised trial correlate this with reduced infectious episodes and shortened length of hospitalisation in patients with lymphoid malignancies. A substantial number of patients with graft failure after bone marrow transplantation also respond to rGM-CSF. The duration of myelosuppression secondary to cancer chemotherapy can be significantly reduced by rGM-CSF which has permitted investigation of antineoplastic dose-intensity escalation. In some haematopoietic disorders (e.g. aplastic anaemia, myelodysplasia and neutropenia secondary to HIV infection and antiviral therapy), rGM-CSF produces clinically useful increases in peripheral blood granulocyte counts, although the effect is generally not sustained after drug withdrawal. The potential for rGM-CSF to stimulate proliferation of the abnormal clone in myelodysplasia and in acute myelogenous leukaemia following induction therapy is of concern. Available data suggest, however, that with appropriate monitoring and exclusion of high-risk patients this serious potential risk can be avoided, and that myelopoiesis is enhanced in such patients by rGM-CSF treatment. Recombinant colony-stimulating factors are a new therapeutic modality; hence many aspects of their use remain to be clarified. Nonetheless, as one of a small group of novel agents rGM-CSF has major potential in the management of myelosuppression secondary to cytoreductive therapy with or without bone marrow transplantation, and in amelioration of disturbed myelopoiesis. It represents an important application of biotechnology to a difficult area of therapeutics.
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PMID:Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). A review of its pharmacological properties and prospective role in the management of myelosuppression. 137 18

ImuVert, a new biological response modifier, was evaluated for toxicity and potential efficacy in patients with advanced cancer. This agent consists of sized, labile, natural membrane vesicles associated with ribosomes derived from Serratia marcescens. ImuVert induces enhanced in vitro macrophage and natural-killer-cell-mediated cytotoxicity, and has demonstrated antitumor activity in palpable animal tumor systems. A group of 39 patients with a variety of tumors, 25 men, 14 women, with a mean performance status (Karnofsky) of 80% and median age of 57 years were entered into this trial. ImuVert was administered subcutaneously weekly for a minimum of 3 weeks. A total of 183 treatments were evaluated. Flu-like systemic toxicities, including fever, chills, nausea, vomiting, diarrhea and hypotension were observed. Erythema, induration and tenderness developed at the injection sites. Myelosuppression, thrombocytopenia, anaphylaxis, rental and hepatic toxicities did not occur. All symptoms resolved within 24 h. Two patients with nodular lymphoma achieved a partial response and two minor responses were seen in patients with glioblastoma and melanoma. On the basis of ImuVert's biological activity, and tolerable toxicity it warrants further clinical investigation.
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PMID:Phase I trial of ImuVert (natural membrane vesicles associated with ribosomes) in patients with advanced cancer. 139 37

In vitro and preclinical in vivo data have shown a synergistic antitumor activity between alpha-interferon and some antiproliferative agents. A phase I study of the concurrent administration of interferon-alpha 2 and mitoxantrone was initiated, to determine the maximum tolerated dose of mitoxantrone given i.v. every 3 weeks in escalating doses combined with a fixed dose of s.c. interferon alpha 2 (6 x 10(6) IU three times per week 3), in patients with advanced solid tumors resistant to conventional chemotherapy. At least three evaluable patients were entered in each dose level of mitoxantrone starting at 4 mg/m2, with no escalations allowed in the same patient. Twenty-seven patients received a total of 101 cycles and five dose-levels were explored (4-6-8-10-12 mg/m2 of mitoxantrone). The dose-limiting toxicities were leukopenia and granulocytopenia at 12 mg/m2 of mitoxantrone, at which dose hematological toxicity occurred in greater than 50% of cases, with one patient presenting grade 4 leuko-granulocytopenia. No severe thrombocytopenia occurred. In the majority of patients transient hepatic enzyme elevations and a flu-like syndrome due to interferon alpha 2 were observed in all dose-levels explored. These observations suggest that the hepatotoxic effects of interferon alpha 2 do not emphasize mitoxantrone side-effects if given simultaneously. When mitoxantrone is administered with 6 x 10(6) IU of interferon alpha 2, the recommended dose for future phase II studies is 10 mg/m2/weeks 3 with escalation up to 12 mg/m2 in selected patients if such a combination is well tolerated in terms of myelosuppression. Regarding therapeutic activity, four out of 25 (16%) cases evaluable for response achieved a partial response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of escalating dose mitoxantrone in combination with alpha-2-interferon in patients with advanced solid tumors. 178 24

Sixty-two patients with biopsy-proven, measurable disseminated malignant melanoma received either the combination IFN-alpha 2A with BCNU (30 patients) or the combination cimetidine with BCNU (32 patients) in parallel noncomparative Phase II trials. From patients receiving IFN-alpha 2A plus BCNU, we observed a 7% response rate: 1 complete response (CR) and 1 partial response (PR) (soft tissue disease with durations of 6.9 and 11.5+ months, respectively). Median time to progression (MTP) was 1.8 months and median survival time (MST) was 3.8 months. Myelosuppression and a flu-type illness were the most common toxicities. From patients receiving cimetidine plus BCNU, the response rate was 16%: 4 PRs (soft tissue disease, 3.8 months; visceral, 2.1, 4.0+, and 9.7 months) and 1 CR (soft tissue, 14.3+ months). MTP and MST were 1.9 and 5.5 months, respectively. Myelosuppression and nausea/vomiting were the most common side effects. Although each of these regimens had great conceptual allure, neither offered any durable impact on the natural history of disseminated malignant melanoma. Nevertheless, alternative combinations of biological response modifiers (BRMs) and BRMs with biochemical modulators or cytotoxic agents may provide some useful alternatives for further clinical investigations.
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PMID:Phase II trial of recombinant leukocyte A interferon (IFN-alpha 2A) plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the combination cimetidine with BCNU in patients with disseminated malignant melanoma. 202 22

Twenty-six patients with advanced cancer received monthly intramuscular recombinant leukocyte A interferon (IFN-alpha 2A), 12 X 10(6) U/m2 daily X 5 with escalating doses of doxorubicin, 25 to 40 mg/m2 on day 3. As anticipated, dose-limiting toxicities were an influenza-type syndrome and myelosuppression. A clinically meaningful and dramatic partial response of hepatocellular carcinoma persisted for 11.5 months associated with an alpha-fetoprotein reduction from 39,000 to 299 ng/ml. For Phase II investigations, the authors recommend the above IFN-alpha 2A dose with doxorubicin, 40 mg/m2, in patients with a performance score of 0 or 1 and no prior chemotherapy or significant radiation therapy which would enhance myelosuppression.
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PMID:Phase I study of recombinant leukocyte A interferon (IFN-alpha 2A, Roferon-A) with doxorubicin in advanced malignant disease. 247 65

The effects and toxicities of interferon alfa are described, and the role of the pharmacist in making decisions and providing education about biologic response modifiers (BRMs) is discussed. Interferons have both direct antitumor activity and extensive effects on the immune system. Two recombinant interferon alfa products--interferon alfa-2a and interferon alfa-2b are available commercially. Indications in FDA-approved labeling for interferon alfa include the treatment of hairy-cell leukemia, acquired immunodeficiency syndrome-related Kaposi's sarcoma, and genital warts; however, it also is being used successfully against early chronic myelogenous leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and previously untreated multiple myeloma. Other malignancies that respond to treatment with interferon alfa are malignant melanoma, ovarian carcinoma, and renal cell carcinoma. The toxic pattern of interferon alfa consists of flu-like symptoms, which are seen at all doses, on all schedules, and in virtually all patients. After repeated dosing, the chronic toxicities of anorexia, weight loss, and malaise and fatigue may develop. Myelosuppression, central nervous system toxicity, increased hepatic enzyme concentrations, nausea and vomiting, and cardiovascular toxicity also are possible. Serum neutralizing antibodies may be formed during therapy; this phenomenon may affect the clinical outcome. Numerous BRMs are being investigated for clinical use, and pharmacists must become conversant in the issues that surround these agents. Areas in which pharmacist involvement and knowledge are important include overall cost, product similarities and differences, dosing and scheduling, drug delivery systems, ways to minimize waste, adverse effects and their management, drug interactions, storage requirements, differences in production and purification techniques among manufacturers, and education of patients and staff.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biologic response modifiers: the interferon alfa experience. 248 96

Based on the demonstration of in vitro and in vivo synergy between cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP), we designed a Phase II trial of Ara-C plus CDDP for patients with advanced squamous cancers of the head and neck and esophagus. Sixteen patients were treated on a unique schedule of continuous-infusion Ara-C, 30 mg/m2/day over 72 h, plus CDDP, 30 mg/m2/day at hours 12, 36, and 60 of the Ara-C infusion. The objective response rate was 38% (95% confidence limits 14-62%), with two patients achieving complete clinical and radiographic response (9 and 27+ months duration) and four partial responses (median duration 4 months, range 1-7 months). There was no CDDP-related nephro- or neurotoxicities, but a flu-like syndrome of anorexia and asthenia was common. Myelosuppression was the dose-limiting toxicity, necessitating Ara-C dose adjustments in 11 cycles of therapy and leading to fatal sepsis in one patient. We conclude that the activity of this combination, though comparable to that of other CDDP-containing regimens, offers no significant therapeutic advantage, and given the excessive hematologic toxicity, should not be investigated further.
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PMID:Combination chemotherapy with cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP) for squamous cancers of the upper aerodigestive tract. 258 30

Trimetrexate glucuronate (TMTX), a non-classic folate antagonist, has been evaluated clinically on several schedules. We studied TMTX given as an i.v. bolus over 5-30 min every 3 weeks in 44 patients with advanced solid tumors; it was given at doses ranging from 20 to 275 mg/m2. The maximal tolerated dose (MTD) on this schedule is 220 mg/m2, which we also recommend as a starting dose for phase II studies in patients without extensive prior therapy. Because of wide individual differences in drug tolerance, dose escalation in 25% increments is recommended for non-toxic patients. The principal dose-limiting toxicity was myelosuppression, although in some patients a flu-like syndrome precluded dose escalation. Significant rash and mucositis also frequently occurred in toxic patients. TMTX plasma concentrations were measured after the first dose and the data were fit by two- or three-compartment mammillary pharmacokinetic models. The TMTX clearance rate was 36.5 +/- 21 ml/min per m2 and did not change with dose; non-linearities with increasing dose were apparent in the steady-state volume of distribution (Vss) and in the terminal disposition half-life (t1/2). The difference between pre-treatment and nadir leucocyte counts was correlated with TMTX dose (r = 0.58; P = 0.0006) and with the area under the concentration vs time curve (AUC) (r = 0.41; P = 0.02). Pre-treatment plasma albumin concentrations correlated weakly with the nadir white blood count (r = -0.36; P = 0.047). Optimal schedules for the administration of TMTX have not been established and phase II trials using both bolus and daily X 5 schedules are under way.
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PMID:A phase I trial of trimetrexate glucuronate (NSC 352122) given every 3 weeks: clinical pharmacology and pharmacodynamics. 275 61

A Phase I study of recombinant gamma-interferon was conducted in 35 patients with advanced malignancy. The schedule was twice weekly administered intravenously. Patients were assigned to six dose levels. The major toxicities were flu-like symptoms and were unrelated to dose. Other adverse reactions, such as myelosuppression, were dose dependent. The addition of a nonsteroidal anti-inflammatory agent did not ameliorate the symptoms at the highest dose level. Antitumor effects occurred in patients with gastric, duodenal, and breast carcinoma.
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PMID:Phase I study of recombinant gamma-interferon (rIFN-gamma). 314 91


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