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)

Eight evaluable patients with cisplatin-resistant non-small cell lung cancer (6 patients), small cell lung cancer (1 patient), or both breast and ovarian cancer (1 patient) were entered on a study to determine whether the addition of nifedipine plus pentoxifylline to cisplatin-based chemotherapy would result in increased chemotherapy efficacy. No patient responded to treatment. Myelosuppression may have been augmented by the nifedipine and pentoxifylline (median granulocyte nadir, 0.3 x 10(9)/L). Two patients developed febrile neutropenia. Nifedipine and pentoxifylline had to be stopped in two evaluable patients due to hypotension, and three additional inevaluable patients withdrew from the study due to nifedipine-pentoxifylline toxicity before receiving their chemotherapy. There was no indication that other types of chemotherapy toxicity were increased by the addition of nifedipine and pentoxifylline. A major problem with the strategy followed in this protocol was that patients whose tumors had failed to respond to cisplatin-based regimens were often too ill to tolerate additional cisplatin, particularly when accompanied by nifedipine-associated hypotension.
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PMID:Addition of pentoxifylline plus nifedipine to chemotherapy in patients with cisplatin-resistant cancers of the lung and other sites. 804 93

Thirty consecutive patients with stage IIIB-IV non small cell lung cancer were treated with a combination of cisplatin 80 mg/m2 on day 1 plus vinorelbine 25-30 mg/m2 on days 1, 8. This cycle was repeated every 3 weeks. The overall response rate was 46%, with 1 patient showing a complete response and 13 patients (43%) a partial response with a mean duration of 8.4+ months. Six patients had a stabilization and 10 progressed. The main toxicities were represented by myelosuppression and nausea/vomiting. Grade 3 leukopenia was seen in 33% of cases, grade 2 thrombocytopenia in 12%, and phlebitis in the injection vein in 16%. Mild constipation was also recorded. The combination of cisplatin plus vinorelbine is quite effective in advanced non small cell carcinoma of the lung, and may be safely given on an outpatient basis.
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PMID:Vinorelbine plus cisplatinum for the treatment of stage IIIB and IV non small cell lung carcinoma. 806 91

Thirty-three patients with limited small cell lung cancer (SCLC) received carboplatin, epirubicin and VP-16 chemotherapy, concurrent 'split course' thoracic radiotherapy, followed by surgery for patients achieving an objective response (OR). High-risk patients and those staged T4-N3 (IIIB) at diagnosis, were excluded from surgery. After induction chemoradiotherapy we obtained 90.9% OR, with 63.3% obtaining complete response (CR). Ten patients (30.3%) were eligible for surgery after induction therapy. Five patients (15.1%) were subjected to surgery and five additional patients refused. Of the five patients who were subjected to surgery, four had a complete response (CR), (three pathological confirmations), and one had a partial response (PR), (unresectable). The median survival time for all patients was 16 months with 12.1% of the long-term survivors still living after 2 years and 9% still living after 3 and 4 years. Toxicity consisted mainly of myelosuppression. This study shows a high activity of the chemotherapy and the chemoradiotherapeutic regimen employed but a low feasibility for adjuvant surgery in SCLC.
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PMID:Carboplatin plus epirubicin plus VP-16, concurrent 'split course' radiotherapy and adjuvant surgery for limited small cell lung cancer. Gruppo Oncologico Centro-Sud-Isole (GOCSI). 808 7

Major modalities of treatment in small cell lung cancer include chemotherapy, radiation therapy and surgery and all of these cause both early and late toxicities. Common toxicities, both early and late, are described in all of the modalities of treatment. Emphasis on new approaches such as the use of colony-stimulating factors to reduce myelosuppression, new antiemetics to make cisplatin and anthracyclines much more tolerable, the use of cardiotoxic anthracyclines such as Epirubicin and emphasis on the incidence of second malignancies in this population, some of which will likely decrease due to decreased use of procarbazine and nitrosoureas along with fewer courses of chemotherapy.
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PMID:Complications associated with the treatment of small cell lung cancer. 808 25

In our study, 72 SCLC patients, 23 with limited and 49 with extensive disease, were treated with carboplatin, epirubicin, and VP-16 (CEV) chemotherapy (CBDCA 300 mg/m2 day 1, EDX 50 mg/m2 day 1, VP-16 100 mg/m2 i.v. days 1-3, every 4 weeks). Patients with limited disease were also subjected to concurrent "split-course" chest radiotherapy followed by surgery in responders if they were not staged IIIB at diagnosis. In limited disease we obtained 96.5% objective responses (OR) with 52.5% complete responses (CR), a median survival of 14 months, with 13% long-term survivors at 30 months. In extensive disease we obtained 83.6% OR with 28.5% CR, and a median survival of 10 months. Toxicity consisted mainly of manageable myelosuppression, especially for limited disease. These data show high activity of CEV chemotherapeutic regimen.
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PMID:Carboplatin, epirubicin, and VP-16 chemotherapy in the treatment of small cell lung cancer. 814 Nov 8

Etoposide is more active in small cell lung cancer when given over 5 days than as a single injection. To examine this concept further, we designed this Phase II study in NSCLC using continuous low-dose oral etoposide. We enrolled 19 patients with measurable disease and the standard eligibility criteria. 16 had no prior chemotherapy. Etoposide was given at a dose of 50 mg by mouth daily. The median duration of therapy was 63 days (14-212 days). Toxicity was mild myelosuppression and GI symptoms. Therapy was discontinued because of progression of disease in 13 patients, toxicity (GI) in 3 patients; intercurrent disease, self-removal, and other reasons in 1 patient each. No complete or partial responses were seen (95% CI: 0-17.6%). The median survival after entry into the trial was 159 days (41-571+ days). We conclude that low-dose continuous oral etoposide is a well-tolerated but ineffective regimen in non-small cell lung cancer.
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PMID:Inefficacy of low-dose continuous oral etoposide in non-small cell lung cancer. 814 Nov 9

In the late sixties the first randomized placebo controlled study with cyclophosphamide demonstrated improved survival in patients with extensive small cell lung cancer (SCLC). Since then chemotherapy has become the mainstay of treatment of SCLC. A number of active combination chemotherapy programs for SCLC were developed during the 1970s and early 1980s. Administration of three or four effective drugs simultaneously appeared to be required for optimal results, but the particular regimen selected was of less importance than the delivery of doses that induced moderately severe but not life-threatening myelosuppression. The drugs chosen for a combination were justified on the basis of single agent activity, difference in mechanism of action and non-overlapping toxic effects. The actual doses were usually the result of feasibility studies in which the doses of all except one drug were held constant. Certain combinations became popular quickly, long before it was appreciated that one of the drugs in the combination added more toxicity than benefit. It is therefore not surprising that the old concept that two drugs in combination are better than one, or three drugs in combination are better than two, is being increasingly criticized. There is recognition that at the time of diagnosis SCLC may already be partially resistant to multiple chemotherapeutic agents and that the strategy simulated by Goldie and Coldman may only partly be applicable to SCLC. Moreover, the development of hematopoietic growth factors has provided a reason to re-evaluate the doses of individual cytostatic agents in current combination regimes and to combine drugs that previously were thought to be incompatible. But even without growth factors, recent investigations with the single agent etoposide and the combination of etoposide and cisplatin have provided arguments against the old theories of "more is better". Drug combinations must preferably be selected on the basis of pharmacokinetic studies. Dose intensity has to be revised and fascinating opportunities will arrive as soon as efficient oral formulations of active drugs, such as platinum, ifosfamide and etoposide become available.
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PMID:Are we moving towards continuous treatment in small cell lung cancer (SCLC)? 816 73

Etoposide is an important anti-neoplastic drug, but the best dose and schedule for its administration remain unknown. The schedule-dependency of etoposide for small cell lung cancer (SCLC) is now proven and it is probably true for other sensitive neoplasms as well (e.g., lymphoma and germ cell tumors). Recent data suggest that an extended schedule of administration (i.e., 14 to 21 days) may be more effective than the standard 3- to 5-day schedule. Several phase II studies with etoposide have demonstrated its activity against several neoplasms. Some have assessed the relationship of etoposide plasma levels to dose, schedule, and tumor responsiveness. Preliminary data suggest that high peak plasma levels (i.e., > 5 to 10 micrograms/ml) are associated with more severe myelosuppression than lower peak plasma levels (i.e., 1 to 3 micrograms/ml). Response and survival rates in previously untreated SCLC patients given low daily doses of etoposide for 14 to 21 days are at least comparable with results achieved with standard etoposide doses given for 3 to 5 days, and the extended etoposide schedule is less toxic than the 3- to 5-day schedule. Preliminary data from several studies suggest that administering low, daily etoposide doses over a prolonged schedule is a superior method of administration. Other studies, including randomized comparisons, are necessary to confirm these observations.
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PMID:Chronic etoposide administration: overview of clinical experience. 822 15

The pharmacokinetics and pharmacodynamics of doxorubicin and its metabolite, doxorubicinol, were studied in 35 adult (mean age, 66 1/2 years) patients with small lung cell cancer after a 1-hour intravenous infusion at a dose ranging from 45 to 72 mg/m2. All patients also received concomitant therapy with cyclophosphamide and vincristine. Serum concentrations were sampled to 48 hours after dosing. Wide interpatient variability was observed for all pharmacokinetic parameters with coefficients of variation for apparent volume of distribution, clearance, and area under the curve (AUC) of 62%, 65%, and 65%, respectively. Four patients with impaired liver function showed a significant (p < 0.05) decrease in clearance (239 versus 666 ml/min/m2) and increases in AUC (4610 versus 1834 ng.hr/ml) and elimination half-life (49.3 versus 25.6 hours) compared with patients with normal hepatic function. A significant relationship was found between systemic exposure of doxorubicin (defined by AUC) and surviving factor of white blood cells (r = 0.57, p = 0.0025). No relationships were noted between doxorubicinol exposure and surviving factor of white blood cells or platelets. These findings show the important relationship between systemic exposure of doxorubicin and the degree of myelosuppression in patients with small cell lung cancer.
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PMID:Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer. 838 3

Seventy patients with previously untreated histologically proven small cell lung cancer (SCLC) were treated with a combination of teniposide 60 mg/m2 intravenously (i.v.) on days 1 through 5 and carboplatin 400 mg/m2 i.v. on day 1 every 28 days for six courses. Patients with limited stage disease, (LD) who achieved a response, subsequently received 2,000 cGy prophylactic cranial and 3,000 cGy involved field thoracic radiotherapy. Of the 70 patients, 62 were evaluable for response: 47 patients (76%) achieved an objective response; 14 of 29 patients (48%) with LD had a complete response (CR), with a partial response (PR) plus CR rate of 76%. Seven of 33 patients (21%) with extensive disease (ED) achieved a CR, with a combined PR and CR rate of 76%. Median time to progression (TTP) for all responders was 292 days (42 weeks). Median duration of survival for all LD patients was 415 days (59 weeks). Survival for LD patients was 88% at 6 months, 61% at 12 months, and 29% at 18 months. Median survival duration for all patients in the study was 311 days (44 weeks), with a survival of 79% at 6 months, 44% at 1 year, and 16% at 18 months. Myelosuppression was the main toxicity, with World Health Organization (WHO) grade 3 or 4 infection occurring in 33% of patients. Two patients died of pneumonia, one complicated by renal failure, and another suffered cardiac arrest related to treatment. The high activity of this drug combination justifies its use as a first-line treatment of previously untreated SCLC.
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PMID:Combination chemotherapy with teniposide (VM26) and carboplatin in small cell lung cancer. 839 86


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