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)

Nineteen patients with a histologically confirmed diagnosis of small cell carcinoma (SCCL) of the lung were entered on trial with a new nitrosourea, 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea (PCNU). All patients had had prior chemotherapy and 42% had received a nitrosourea. No patient had a major response to treatment with PCNU and only one patient had a minor response of short duration. Myelosuppression, particularly thrombocytopenia, was the major dose-limiting side effect. PCNU did not appear to be of benefit in patients with recurrent SCCL.
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PMID:Phase II trial of 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea in small cell cancer of the lung. 609 39

Forty patients with extensive small cell lung cancer randomly received either high-dose or low-dose methotrexate with leucovorin rescue in combination with cycles of cyclophosphamide, doxorubicin, and vincristine alternating with cycles of VP-16, vincristine, and hexamethylmelamine. Nineteen patients were treated with the high-dose methotrexate regimen, and 21 received the low-dose methotrexate treatment protocol; both treatment groups were similar in median age, performance status and spread of disease. Response rates (74 percent for high-dose therapy; 67 percent for low-dose therapy), median survival (nine months versus nine months), and overall survival were similar for the two treatment groups. Myelosuppression was equivalent in both treatment groups but moderate to severe mucositis developed more often when patients were treated with the high-dose methotrexate regimen as compared with low-dose methotrexate therapy (p less than 0.001). Central nervous system recurrences developed after three patients received high-dose methotrexate therapy. This study indicates that when used with other antineoplastic agents, high-dose methotrexate therapy does not improve the remission rate or survival nor does it decrease central nervous system metastasis in patients with small cell lung cancer when compared with standard doses of methotrexate; high-dose methotrexate is associated with greater cost and toxicity.
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PMID:Randomized study of high-dose versus low-dose methotrexate in the treatment of extensive small cell lung cancer. 628 61

Sixteen previously treated patients received AZQ in a phase II study to test therapeutic efficacy in refractory small cell lung cancer. The dose and schedule of AZQ was 20 mg/m2 day 1 and 8, with treatments repeated every 28 days. No objective responses were noted among 16 evaluable patients. Myelosuppression was the major toxicity. AZQ does not appear to have antitumor activity in patients with previously treated small cell carcinoma.
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PMID:Phase II trial of aziridinylbenzoquinone (AZQ) in patients with refractory small cell carcinoma of the lung. 629 94

Etoposide (VP 16) is a semi-synthetic derivative of 4'- demethylepipodophyllotoxin , a naturally occurring compound synthesized by the North American May apple (Podophyllum peltatum ) and the Indian species Podophyllum emodi Wallich . Although podophyllotoxins are classical spindle poisons causing inhibition of mitosis by blocking mitrotubular assembly, etoposide inhibits cell cycle progression at a premitotic phase (late S and G2), probably via inhibition of DNA synthesis. There appears to be a selective antileukemic dose response relationship when compared to normal hematopoietic elements. Etoposide is effective when administered orally at about twice the recommended parenteral dosage. Schedule dependency in both animal models and clinical trials has been observed; multiple dosing over three to five consecutive days is superior to weekly single dose administration. Etoposide's dose-limiting toxicity is myelosuppression (leukopenia), which is quite predictable; alopecia and Gl toxicity (nausea, vomiting, stomatitis) occur in about 20-30% of patients given recommended dosages. Etoposide appears to be one of the most active drugs for small cell lung cancer, testicular carcinoma (the Food and Drug Administration approved indication), ANLL and malignant lymphoma. Etoposide also has demonstrated activity in refractory pediatric neoplasms, hepatocellular, esophageal, gastric and prostatic carcinoma, ovarian cancer, chronic and acute leukemias and non-small cell lung cancer, although additional single and combination drug studies are needed to substantiate these data. Its contribution in front-line combination chemotherapeutic regimens for these cancers will be better defined in the forthcoming years. Etoposide appears to have minimal activity in breast cancer and, based on current data, it is inactive against malignant melanoma, colorectal adenocarcinoma and cancer of the head and neck, although the dosage and schedules used in many of the Phase II studies may have been suboptimal.
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PMID:Etoposide: a semisynthetic epipodophyllotoxin. Chemistry, pharmacology, pharmacokinetics, adverse effects and use as an antineoplastic agent. 632 63

Thirty-two males with recurrent small cell lung cancer after previous remission were treated with vindesine (3-4 mg/m2) plus cisplatin (60-100 mg/m2). Six patients (19%) responded to this therapy with two complete (CR) and four partial remissions. Minor responses were seen in another ten patients (32%). In patients with CR survival from start of treatment lasted 61 and 38 weeks; in patients who did not achieve CR median survival was 12 weeks. Nausea and vomiting were the predominant side effects, while only mild to moderate myelosuppression was noted. The vindesine and cisplatin regimen demonstrated significant activity against heavily pretreated small cell lung cancer, although chemotherapeutic response was poor in regions of prior irradiation.
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PMID:Treatment of recurrent small cell lung carcinoma with vindesine and cisplatin. 632 37

In an attempt to clarify the relationship between myelosuppression and the response to chemotherapy, 127 cases of small cell lung cancer were reviewed. These patients received a total of four different drug combinations. The myelosuppression of the first chemotherapy course was reduced with the addition of one or two drugs to the basic Cytoxan (cyclophosphamide)-vincristine drug combination without a change in the incidence of remission. Patients with good performance status have less severe leukopenia and thrombocytopenia than those with poor performance status. Patients with complete and partial response have slightly more severe thrombocytopenia but not leukopenia than the nonresponders. It is concluded that the burden of tumor has a direct effect on the incidence of remission and myelosuppression suggesting that more severe toxicity is necessary to obtain remission in poor risk patients. Myelosuppression is required before assessing whether the patient has received an adequate amount of chemotherapeutic agent but is only a weak prognostic factor.
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PMID:The influence of myelosuppression on the response to chemotherapy in small cell bronchogenic carcinoma. 632 4

The treatment of solid tumours with high-dose chemotherapy using alkylating agents either as single agents or in combination schedules has received increasing attention from clinical investigators in recent years. This has frequently been given in association with autologous bone marrow support, a technique which appears to ameliorate myelosuppression that might otherwise be dose-limiting, and which thus may allow dose escalation into a range previously not reached. Despite this ability, and in spite of much experimental evidence from drug-sensitive animal tumours that increasing doses result in increased response rates, no major impact has yet been made in the therapy of solid tumours using this form of therapy. In addition, the use of high-dose schedules has seen the emergence of extramedullary manifestations of drug toxicity which were not encountered at conventional doses. Nevertheless, there are some encouraging data from reports in certain tumours, including small cell lung cancer, testicular cancer, ovarian cancer, and lymphoma, and further studies are clearly indicated. These should probably be restricted to certain drug-sensitive tumours, and should include an examination of the role of high-dose chemotherapy as consolidation treatment, following conventional induction therapy for selected tumour types. This form of treatment may yet provide an important contribution to the control of human solid tumours, but much further work, probably with combination drug schedules, is required.
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PMID:Intensive chemotherapy for solid tumours--current clinical applications. 676 Oct 9

Methotrexate (MTX) in high doses (3 to 7.5 g/m2) with leucovorin rescue (HDMTX-LCV) can be delivered on a weekly basis in a setting of proper pharmacologic monitoring. Myelosuppression occurs in 28 per cent of the patients and in 8 per cent of the courses and usually results from delayed MTX excretion secondary to mild reversible nephrotoxicity. The incidence of tumor regression was 50 per cent in head and neck cancer; 59 per cent in non-Hodgkin's lymphoma; 40 per cent in small cell lung cancer; 24 to 50 per cent in breast cancer and 50 per cent in osteogenic carcinoma, for an over-all response rate of 39 per cent (70 of 178) in patients with disseminated cancer. HDMTX-LCV is not recommended for the conventional treatment of metastatic cancer because of the potential for toxicity and the fact that the response rates cited are probably not superior to those which can be achieved by conventional doses of MTX. However, the relative lack of myelosuppression and mucositis, when compared to conventional unrescued MTS, and the achievement of therapeutic concentrations of MTX in the central nervous system with the HDMTX-LCV program have led to its incorporation into clinical trials of combination chemotherapy.
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PMID:High dose methotrexate with leucovorin rescue. Rationale and spectrum of antitumor activity. 696 19

To study the toxicity and efficacy of simultaneous cisplatin chemotherapy and radiation therapy, 13 patients with metastatic solid tumors were treated with cisplatin on a weekly, outpatient basis during palliative radiation therapy. The dose of cisplatin ranged from 20 to 50 mg/m2 weekly, with most patients receiving 40 mg/m2. Radiation therapy was administered in a variety of dose-fraction schedules. Toxic effects were moderate and consisted of emesis (12 patients), transient elevation off BUN (three patients), myelosuppression (three patients), and radiation reactions (two patients). Twelve of 13 irradiated lesions (91%) responded with at least a 50% reduction in biperpendicular diameter. Four of the six patients with metastatic melanoma had complete regression of treated lesions; another melanoma patient had a partial response. Responses were also seen in patients with mesothelioma, bladder cancer, squamous cell carcinoma of the head and neck, and oat cell lung cancer. Only one responding patient has had disease progression in the treated field after 2+ to 7+ months of followup; two other patients have died of disseminated disease. Weekly cisplatin administration during radiotherapy deserves further evaluation, especially in the primary management of unresectable tumors that are responsive to cisplatin alone.
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PMID:Simultaneous treatment with cisplatin and radiation therapy for advanced solid tumors: a pilot study. 719 3

A phase I study was conducted to define the maximally tolerated dose and toxicity profile of the ifosfamide/carboplatin/etoposide/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (ICE-T) regimen in advanced lung cancer. This chemotherapy program uses paclitaxel given as a 24-hour continuous infusion in conjunction with full-dose ICE chemotherapy with growth factor support. The dosage of paclitaxel was escalated from 75 to 225 mg/m2. Thirty-four patients have been accrued to date onto this study. Because hematologic dose-limiting toxicity was defined in terms of neutropenia and/or thrombocytopenia exceeding 7 days' duration, no patient demonstrated what was defined by the protocol as dose-limiting toxicity. Nonetheless, substantial hematologic toxicity was observed. Overall, 26% had fever and neutropenia, 56% had grade 4 neutropenia, and 26% had grade 4 thrombocytopenia. In all cases, hematologic toxicity was short term and reversible. While grade 3 and 4 myelosuppression was frequently observed, it was not dose related (in terms of paclitaxel dosage). Nonhematologic toxicity also was not dose related and, with only a few exceptions, was not clinically significant. Among 27 patients evaluable for response, 41% achieved an objective response, including 15% with a complete response. All of five patients with small cell lung cancer responded (including two with a complete response). Among 22 patients with non-small cell lung cancer, 27% achieved an objective response (also including two with a complete response). The results of this study suggest that with growth factor support, it is possible to safely administer full-dose, single-agent paclitaxel in conjunction with full-dose ICE chemotherapy. We will soon be initiating a phase II study of the ICE-T regimen using paclitaxel at 225 mg/m2 as a 24-hour continuous infusion in advanced lung cancer. We will also conduct a phase I study of ICE-T, with paclitaxel administered as a 3-hour continuous infusion.
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PMID:A phase I study of ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer. 754 29


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