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)

A phase I study of human lymphoblastoid interferon (IFN-alpha) was undertaken in patients with acute leukaemia and other malignancies. The pharmacokinetics of intravenous IFN-alpha were also investigated. IFN-alpha was administered to two patients by intravenous (IV) bolus injection at a dose of 5 X 10(6) U/m2; and to a further 37 patients (40 cycles) by continuous intravenous infusion (IVI) for 5, 7, or 10 days at doses ranging from 5 to 200 X 10(6) U/m2/day. Pyrexia, general malaise, anorexia, and rigors were observed at all dose levels; three patients became hypotensive. Myelosuppression occurred in all patients, including seven without bone marrow infiltration. Transient rises in alkaline phosphatase and transaminases (SGOT) were observed in patients receiving daily doses greater than 30 X 10(6) U/m2. Dose-limiting central nervous system toxicity, hyperkalaemia, and hypocalcaemia were encountered at 200 X 10(6) U/m2. In six patients with acute leukaemia there was a fall in the number of circulating leukaemic blasts and in one patient with acute myelogenous leukaemia (AML) the degree of bone marrow infiltration decreased from 99% to less than 5% with cellularity returning to normal. Serum levels of IFN above 1,000 U/ml were achieved with daily doses above 30 X 10(6) U/m2 given by IVI. The maximum safely tolerated daily dose, 100 X 10(6) U/m2 administered for 7 days, is appreciably higher than that used in most previous studies, although even at this level considerable toxicity may be encountered.
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PMID:A phase I study of human lymphoblastoid interferon administered by continuous intravenous infusion. 717 12

Human fibroblast interferon(HFIF) was used in 26 patients with various malignant diseases, most of whom had previous chemotherapy. The dosages used were 3 X 10(6) IU or 6 X 10(6) IU of HFIF i. v. daily. Out of 24 evaluable patients, there were 2 partial remissions (CLL 1 and multiple myeloma 1), and 7 stable diseases (multiple myeloma 2, stomach cancer 2, non-Hodgkin's lymphoma 1, CLL 1 and malignant melanoma 1). The majority of the patients experienced fever exceeding 38 degrees C and chills, which became uncommon within several days of treatment. Other side effects included myelosuppression, general malaise, anorexia, hepatic dysfunction and renal dysfunction, which were mild and tolerable.
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PMID:[Clinical effects of human fibroblast interferon on malignant tumors]. 718 62

Two clinical studies were undertaken to study the toxicity profile and effects of interleukin-3 (rhIL-3) on chemotherapy-induced myelosuppression. Fifteen patients with recurrent ovarian carcinoma were treated with high dose carboplatin (800 mg m-2). All patients received 5.0 micrograms/kg/d rhIL-3 subcutaneously but timing and duration of rhIL-3 treatment differed. Constitutional symptoms were the major toxicity and in addition to the carboplatin-induced nausea and vomiting the combination was poorly tolerated. In 5/15 patients receiving high dose carboplatin rhIL-3 administration was discontinued due to nephrotoxicity (2 x), hypotension, severe malaise and bone pain. In this study, rhIL-3 ameliorated chemotherapy-induced neutropenia as well as thrombocytopenia and reduced the requirement for platelet transfusions in the second cycle of chemotherapy. However, rhIL-3 failed to prevent cumulative platelet toxicity. In the second study 12 patients with small cell undifferentiated cancers were treated with carboplatin, etoposide and ifosfamide. Three dose levels of rhIL-3 were explored (0.125, 5.0 and 7.5 micrograms/kg/d). In this study, toxicity of the treatment was mild, however, no beneficial haematologic effects of rhIL-3 could be demonstrated. In conclusion, the haematological effects of rhIL-3 were modest and dependent on the chemotherapeutic regimen, timing and duration of rhIL-3 treatment (in relation to the expected nadir). In general rhIL-3-induced toxicity was mild, but combination with high dose carboplatin could be hazardous if rhIL-3 is initiated at 24 h after the cytostatic agent.
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PMID:Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours. 769 22

The dose limiting toxicities of the short infusion trial of the dacarbazine analog, CB10-277, were nausea and vomiting which appeared to be related to the peak plasma level of the parent drug. In addition, based on mouse studies, these dose limiting toxicities occurred at a less than optimal level of the monomethyl metabolite, the presumed species required for antitumour activity. An alternative schedule that would avoid the parent drug peak plasma levels of short infusion, while possibly allowing an increase in the amount of monomethyl metabolite produced was considered. Thus, a 24 h continuous infusion schedule, repeated every 21 days was explored. Twenty-two patients received 42 courses with a dose range of 4,700-15,000 mg m-2. The dose limiting toxicity was myelosuppression (leucopenia and thrombocytopenia). Although nausea and vomiting also occurred, it was manageable with routine antiemetic therapy. Other toxicities included diarrhoea, hallucinations, malaise, muscle ache, headache and flushing and all were < or = WHO grade 2. Pharmacokinetic studies were performed with 13 courses which included all dose levels. The mean t1/2 of the parent drug was 178 min. Area under the concentration x time curve (AUC) at the highest dose for the parent drug and the monomethyl metabolite were 2,350 and 9 mM x minutes, respectively. This monomethyl metabolite AUC and the associated myelosuppression showed a more favourable comparison to the preclinical data determined in mice than the results from the short infusion trial of CB10-277. Therefore, the recommended Phase II dose and schedule of this drug was 12,000 mg m-2 given by 24 h continuous infusion.
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PMID:Phase I trial with pharmacokinetics of CB10-277 given by 24 hours continuous infusion. 843 68

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)
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PMID:Gynecological malignancies. 863 1

A multi-institutional cooperative group trial was undertaken by the Cancer and Leukemia Group B (CALGB) to evaluate the efficacy of the combination of cisplatin and intravenous etoposide for the treatment of metastatic or recurrent non-small cell lung cancer (NSCLC). The doses used were those previously determined to be the maximally tolerated dose of this drug combination. Forty patients were entered into the trial, 37 of whom were eligible for evaluation. Cisplatin (35 mg/M2/day for 3 days) and etoposide (200 mg/M2/day for 3 days) were administered every 28 days for a planned 6 cycles of therapy. Sixteen of 37 evaluable patients (43%) responded to therapy. Myelosuppression was the dominant toxicity, with 89% of the patients experiencing grade 4 neutropenia, and nearly half grade 3 or 4 thrombocytopenia. Median survival was 8.5 months, with 30% of the patients alive at 1 year and 10% alive at 2 years. Malaise, fatigue, and peripheral neuropathy were the other major toxicities. The combination of etoposide at the dose of 200 mg/M2/day for 3 days and cisplatin at 35 mg/M2/day for 3 days is a highly potent combination against metastatic non-small cell carcinoma.
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PMID:Etoposide (VP-16) and cisplatin at maximum tolerated dose in non-small cell lung carcinoma: a Cancer and Leukemia Group B study. 871 68

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

Experimental data have suggested that the pineal hormone melatonin (MLT) may counteract chemotherapy-induced myelosuppression and immunosuppression. In addition, MLT has been shown to inhibit the production of free radicals, which play a part in mediating the toxicity of chemotherapy. A study was therefore performed in an attempt to evaluate the influence of MLT on chemotherapy toxicity. The study involved 80 patients with metastatic solid tumors who were in poor clinical condition (lung cancer: 35; breast cancer: 31; gastrointestinal tract tumors: 14). Lung cancer patients were treated with cisplatin and etoposide, breast cancer patients with mitoxantrone, and gastrointestinal tract tumor patients with 5-fluorouracil plus folates. Patients were randomised to receive chemotherapy alone or chemotherapy plus MLT (20 mg/day p.o. in the evening). Thrombocytopenia was significantly less frequent in patients concomitantly treated with MLT. Malaise and asthenia were also significantly less frequent in patients receiving MLT. Finally, stomatitis and neuropathy were less frequent in the MLT group, albeit without statistically significant differences. Alopecia and vomiting were not influenced by MLT. This pilot study seems to suggest that the concomitant administration of the pineal hormone MLT during chemotherapy may prevent some chemotherapy-induced side-effects, particularly myelosuppression and neuropathy. Evaluation of the impact of MLT on chemotherapy efficacy will be the aim of future clinical investigations.
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PMID:Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin. 906 12

Twenty-nine patients with persistent, recurrent and/or metastatic squamous cell carcinoma of the head and neck were treated daily for five days at three-week intervals with topotecan 1.5 mg/m2. Four patients received prior chemotherapy, 23 prior surgery and 29 prior radiation therapy. Of the 29 eligible patients, 8 patients were not evaluable for response and were assumed to be non-responders. Of the remaining 21 evaluable patients, there were zero responses (0%, 95% confidence interval [0,.12]). The most common toxicities were myelosuppression, dyspnea and malaise/fatigue/lethargy. Topotecan has limited activity in advanced head and neck cancer with this dose and schedule.
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PMID:Evaluation of topotecan in patients with recurrent for metastatic squamous cell carcinoma of the head and neck. A phase II Southwest Oncology Group study. 915 77

An early Phase II study with TUT-7 (menogaril), a new anthracycline antitumor antibiotic, was conducted in patients with various malignant tumors at 81 departments of 65 institutions nationwide. One course of TUT-7 treatment consisted of seven (7) or fourteen (14) consecutive days of administration at 75 or 100 mg/body/day with two-week drug withdrawal; at least two courses of treatment were given in principle. Among the 165 patients registered, 145 patients were eligible and 128 patients were evaluable for antitumor efficacy. In 11 patients with malignant lymphoma, one (1) had CR and five (5) had PR (54.5%); in three (3) patients with prostate cancer, one (1) had PR (33.3%); and in 12 patients with uterine cervical cancer, two (2) had PR (16.7%). Adverse drug reactions frequently observed were digestive organ disorders (anorexia and nausea/vomiting) and malaise. The abnormality in laboratory tests observed frequently was myelosuppression (leukopenia and neutropenia).
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PMID:[TUT-7 early phase II clinical study for various solid tumors and hematologic malignancies]. 927 44


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