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)

Thirty-three patients with multiple myeloma (11 untreated, 15 refractory and seven relapsed patients) have received vincristine and adriamycin infusion therapy with oral dexamethasone (VAD). The median number of course received was five. In addition 16 patients with lymphoid malignancy have received a median of four courses of VAD. Three patients who relapsed after VAD have received further VAD therapy making 52 patient treatments assessable for toxicity. Ten per cent had nausea, 4 per cent vomiting, 4 per cent total alopecia, 25 per cent constipation, 33 per cent paraesthesiae, 8 per cent proximal myopathy, 33 per cent dyspepsia, 23 per cent proven bacteraemia, and 19 per cent chest infections. Infections were not usually associated with neutropenia. Shingles was seen in four patients with myeloma, but none of the patients with lymphoid malignancy. The response rate in myeloma was 9/11, for previously untreated patients, 3/7 for relapsed, and 8/15 for refractory patients. Responses have been seen in other lymphoid malignancies-1/2 patients with relapsed acute lymphoblastic leukaemia had a complete remission. Two out of seven patients with chronic lymphocytic leukaemia achieved a partial remission, and a further three had a clinical improvement. Three out of six patients with non-Hodgkin lymphoma and one patient with macroglobulinaemia achieved a partial remission.
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PMID:VAD chemotherapy--toxicity and efficacy--in patients with multiple myeloma and other lymphoid malignancies. 311 84

Vindesine, a newer vinca alkaloid derivative, underwent a phase I clinical evaluation in 68 humans with advanced, refractory malignancies. Patients received single total doses ranging from 2 to 12.5 mg, repeated every 1-2 weeks. Dose-limiting myelosuppressive, gastrointestinal, and neurologic toxic effects were observed at higher doses. They consisted predominantly of neutropenia, constipation leading, on occasion, to paralytic ileus, and peripheral neuropathy. Total doses of 7.5-10 mg (equivalent to 4-5 mg/m2), repeated every 2 weeks, well-tolerated. There were two partial remissions in patients with acute leukemia and prior vincristine therapy, two minor responses in patients with renal cell carcinoma, one minor response in a patient with squamous cell carcinoma of the esophagus, and one minor response in a patient with squamous cell carcinoma of the lung. Vindesine is well-tolerated by man, although it shares some of the toxic manifestations of vinblastine and vincristine. Its efficacy in some patients who were no longer responsive to vincristine therapy suggests a lack of clinical cross-resistance between these compounds.
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PMID:Initial clinical studies of vindesine. 626 96

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.
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PMID:Thalidomide as salvage therapy for chronic graft-versus-host disease. 757 70

A phase I-II clinical trial was conducted to determine the maximum-tolerated dose (MTD) of oral cyclosporine (CsA) and vinblastine in patients with metastatic renal cell cancer (RCC) as well as to estimate the response rate. Sixteen patients received a 5 mg/kg oral loading dose of CsA followed by 3 days of CsA in 4 divided daily doses escalating from 10 mg/kg per day up to 17 mg/kg per day. Vinblastine (Vbl) was administered as an intravenous bolus on the morning of the 3rd day with dose escalation from 6 to 10 mg/m2. Cycles were repeated every 4 weeks until tumor progression. Forty-nine cycles of CsA with vinblastine were administered. The maximum tolerated dose of Vbl was 10 mg/m2, with neutropenia as the dose-limiting toxicity resulting in one death. CsA could not be escalated above 17 mg/kg per day because of nausea and vomiting. Other toxicities included constipation (100%), malaise (100%), temporary increase in pain (36%), and one seizure that may have been drug-related. There were no clinically significant changes in renal function or serum bilirubin. Mean peak whole-blood CsA level at the highest CsA dose level was 919 ng/ml (range: 414-1,827) with a trough prior to Vbl injection of 451 ng/ml (range: 128-1,229). There were no tumor responses. The combination of oral CsA and Vbl is not nephrotoxic but is poorly tolerated. In most patients optimal blood levels of CsA for reversal of MDR cannot be reliably achieved, and vinblastine dose intensity must be compromised because of the significant toxicity of this regimen.
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PMID:Phase I-II study of vinblastine and oral cyclosporin A in metastatic renal cell carcinoma. 774 14

Vinca alkaloids are widely used in the medical treatment of breast cancer. Our study aimed to evaluate the therapeutic activity of a new vinca alkaloid derivative, S12363 (vinfosiltine), which is 36 and 72 times more cytotoxic in vitro than vincristine and vinblastine, respectively. Because phase I studies did not allow a choice of the best treatment schedule, a randomization was performed between two schedules with the same dose intensity, that is, 0.3 mg/m2 given weekly or 0.6 mg/m2 given every 2 weeks. A total of 16 patients with advanced breast cancer who had failed a first-line treatment without any vinca alkaloid were entered in the study. Additionally, 6 women received the bimonthly regimen as first-line treatment of advanced breast cancer. Altogether, 17 patients received, prior to vinfosiltine, an anthracycline-based regimen given either as adjuvant (n = 4) or as first-line palliative treatment (n = 13). All 22 patients were evaluable for both toxicity and response. Neutropenia was the main toxic event (maximal toxicity per patient) with grade 3 (WHO) toxicity developing in 7/22 patients and grade 4, in 8/22. Other severe toxicities included leukopenia (n = 9), anemia (n = 1), diarrhea (n = 1), constipation (n = 1), and fatigue (n = 1). No patient achieved a complete or partial response. Vinfosiltine does not appear to have significant single-agent activity in advanced breast cancer at the doses and the schedules used in our study.
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PMID:Phase II study of a new vinca alkaloid derivative, S12363, in advanced breast cancer. 788 62

A multicenter early Phase II clinical study of KW-2307, a new vinca alkaloid derivative, in patients (pts) with lung cancer was conducted in 15 hospitals. Ninety-seven pts were enrolled, among whom 95 were eligible. Seventy of the eligible pts had non-small cell cancer (NSCLC) and 25 had small cell cancer (SCLC). PR was obtained in 13 (18.6%) of NSCLC pts and 3 (12%) of SCLC pts. Only those who had no previous chemotherapy showed PR in NSCLC pts, and the response rate in these pts was 29.5% (13/44). As to the correlation between dosage and tumor effect, a better effect was exhibited at higher doses, with response rates of 21.7% (5/23) and 38.1% (8/21) at 20 mg/m2 and 25 mg/m2, respectively. The major adverse effect of this drug was leukopenia (neutropenia), which was Grade 3 or 4 in many cases. Recovery from this complication, however, was rapid. Other adverse effects included mild hepatic dysfunction, anorexia, nausea/vomiting, fever, general fatigue, phlebitis and constipation. The incidence of peripheral nervous disorder such as the paresthesia commonly observed with vinca alkaloids, was as low as 10%, and the symptoms, if any, were mild.
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PMID:[Early phase II clinical study of KW-2307 in patients with lung cancer. Lung Cancer Section in KW-2307 Study Group]. 818 36

Vinorelbine tartrate (Navelbine, Burroughs Wellcome Company, Research Park, NC) is a semisynthetic analog of vinblastine that has been approved by the Food and Drug Administration for use in the treatment of advanced, unresectable non-small cell lung cancer. It has a favorable safety profile and can safely and easily be administered in the outpatient setting on a weekly basis. The major toxicity is severe, granulocytopenia (absolute neutrophil count < 500 cells/mm3), that occurs in approximately 40% of treated patients. This granulocytopenia is rapidly reversible, and does not increase in severity with subsequent cycles. Despite the high incidence of granulocytopenia, only about 8% of patients require hospitalization for the treatment of febrile neutropenia. This article also reviews information concerning the incidence and management of the other major side effects including constipation, paresthesias, decreased deep tendon reflexes, myalgia, and injection site reactions. Guidelines for the safe administration of this agent along with suggestions for patient education are also presented. The potential significance of the impact that this new agent may have in the treatment of advanced, unresectable non-small cell lung cancer and advanced breast cancer is stressed.
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PMID:Vinorelbine tartrate: a promising new chemotherapeutic agent. 870 38

The antineoplastic agent mitoxantrone in combination with a corticosteroid (either prednisone or hydrocortisone) has shown clinical efficacy as palliative treatment for a proportion of patients (about 35 to 40%) with hormone-resistant advanced prostate cancer, a disease which predominantly affects elderly men and for which few systemic treatment options are available. Palliative end-points including pain relief, decreased analgesic use and reduced prostate specific antigen levels (a marker of tumour response) are reached in a greater percentage of patients receiving combination therapy than corticosteroid alone. In addition, there are generally greater improvements in quality-of-life parameters in mitoxantrone recipients. However, combined treatment offers no survival advantage over corticosteroid monotherapy. Neutropenia is the most common toxicity associated with mitoxantone therapy and may necessitate dosage reduction in some patients. Otherwise, mitoxantrone generally has a more favourable tolerability profile than has been established for other cytotoxic agents such as doxorubicin with regard to acute adverse events (e.g. nausea/vomiting, anorexia, constipation, alopecia, malaise/ fatigue, oedema) and cardiac toxicity. In conclusion, administration of mitoxantrone plus a corticosteroid can provide palliation for some elderly patients with hormone-resistant advanced prostate cancer, and is thus a valuable first-line treatment for this indication.
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PMID:Mitoxantrone. A review of its pharmacology and clinical efficacy in the management of hormone-resistant advanced prostate cancer. 920 52

This nonblinded, multicenter, randomized phase III study compares the median time to progression (primary endpoint), response rate, and quality of life, safety, and survival of docetaxel (Taxotere) vs mitomycin (Mutamycin) plus vinblastine (Velban) in patients with metastatic breast cancer in whom previous anthracycline-containing chemotherapy has failed. Patients were randomized to receive an intravenous infusion of either 100 mg/m2 of docetaxel for 1 hour every 3 weeks, or 12 mg/m2 of mitomycin every 6 weeks plus 6 mg/m2 of vinblastine every 3 weeks. This preliminary analysis presents data on 200 patients among 392 patients recruited. Median time to progression was longer in the group treated with docetaxel compared with the mitomycin/vinblastine group (17 vs 9 weeks). The overall response rates were higher with docetaxel (28% vs 13%, respectively), and fewer patients in the docetaxel group had progressive disease as their best overall response (29% vs 48%). As expected, thrombocytopenia was more common in the mitomycin/vinblastine group, and neutropenia occurred more frequently in the docetaxel group. Severe fluid retention in the docetaxel group (8.7%) resulted in treatment discontinuation in 5 patients (5%). Severe thrombocytopenia (12%) and constipation (6%) led to treatment discontinuation in 7 and 3 patients, respectively, in the mitomycin/vinblastine group. Based on this preliminary analysis, docetaxel appears to be equally as safe as and more active than mitomycin/ vinblastine in patients with metastatic breast cancer in whom previous anthracycline-containing chemotherapy has failed. These results are subject to cautious interpretation because this analysis was conducted on the first 200 patients who finished the study treatments, and these preliminary results may underestimate response and overstate treatment discontinuation rates. Thus, the final analysis on the entire patient population is necessary to confirm these preliminary findings.
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PMID:Docetaxel vs mitomycin plus vinblastine in anthracycline-resistant metastatic breast cancer. 936 38

CI-980 is a synthetic mitotic inhibitor that binds to the colchicine binding site of tubulin. It demonstrates broad activity against human and murine tumor models and shows no cross resistance with tumor models whose mechanism of resistance is mediated by P-glycoprotein (MDR-1). A phase I study was completed in 25 patients with solid tumors using a 24-hour infusion schedule, with courses repeated every 3 weeks. Eight dose levels were tested between 1.2 and 15.6 mg/m2. The maximum tolerated dose was 14.4 mg/m2. Neutropenia was dose-related but not dose-limiting; thrombocytopenia was infrequent. CNS toxicities were dose-limiting and consisted of dizziness, headache, loss of coordination, loss of consciousness, nervousness, and other symptoms. These events occurred near the end of the infusion and were reversible, usually within 24 hours. One patient who was to be treated at dose level 8 (intended dose was 19.2 mg/m2; actual dose was 15.6 mg/m2) became encephalopathic prior to completion of the infusion. Other adverse events included gastrointestinal toxicities (nausea, vomiting, anorexia, constipation, stomatitis, dyspepsia, bleeding, cheilitis), IV site erythema, fever, and fatigue. A partial response was observed in one patient with colon cancer and reductions in CA-125 levels were observed in 2 patients with ovarian cancer. Pharmacokinetics were linear and dose-proportional. Results indicate high systemic clearance and wide tissue distribution. Mean pharmacokinetic parameter values: T1/2 = 5.52 hours, plasma clearance 1163 mL/min/m2, and Vdss 376 L/m2.
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PMID:A phase I trial and pharmacokinetic evaluation of CI-980 in patients with advanced solid tumors. 938 46


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