Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data are presented on the general and hematological toxicity of a cisplatin (DDP), 5-fluorouracil (5-FU) and alpha interferon (IFN-alpha) association in patients with stage III B or IV non small cell lung cancer (NSCLC). Twenty patients received DDP (100 mg/mq i.v., day 1) and 5-FU (750 mg/mq/day i.v. continuous infusion, days 1 to 4). In ten of these patients IFN-alpha (3 MU s.c., three times weekly, days 1 to 21) was added. General and hematological toxicity was of a similar degree in both groups. Recombinant granulocyte colony stimulating factor (G-CSF; 5 micrograms/kg b.w. s.c. days 7 to 18) induced a sharp increase in peripheral blood GM-CFU level in patients receiving DDP and 5-FU but not in DDP, 5-FU, IFN-alpha treated patients. The results appear to indicate that IFN-alpha modulation of a DDP, 5-FU combination induces an acceptable degree of toxicity.
 ...
PMID:Cisplatin, 5-fluorouracil and alpha interferon in non small cell lung carcinoma: a toxicity study. 751 37

The purpose of this work was to determine the maximum tolerated (phase II) dose of melphalan and etoposide that can be given in conjunction with autologous BM re-infusion in patients who have refractory or relapsed solid tumors. Twenty-six patients with refractory or relapsed breast cancer (n = 15), small cell lung cancer (n = 1), ovarian cancer (n = 3), colorectal cancer (n = 3) or malignant melanoma (n = 4) were enrolled and treated in this phase I study. Patients ranged in age from 31 to 60 years (median 44.5 years). Melphalan 180 mg/m2 (60 mg/m2/day for 3 consecutive days i.v. over 30 min) and etoposide 1200-3600 mg/m2 (400-1200 mg/m2/day for 3 consecutive days i.v. over 4 h) were given followed by autologous BM infusion 60-72 h after completion of chemotherapy. Ten patients received GM-CSF or G-CSF therapy after marrow re-infusion. Regimen-related toxicities included fever, pancytopenia, mucositis, nausea, vomiting, diarrhea, esophagitis, hepatic dysfunction and infection. Neutrophils recovered to > 500 x 10(6)/l and platelets recovered to > 20 x 10(9)/l (without transfusions) a median of 17 days and 20.5 days after marrow infusion, respectively. Dose-limiting toxicity occurred at an etoposide dose of 3600 mg/m2, since 4 of 6 patients treated at this dose level experienced grade 4 NCI Common Toxicity Criteria (mucositis (n = 3) and infection (n = 1)). Complete responses were noted in 7 patients (breast cancer (n = 5), colorectal cancer (n = 1) and melanoma (n = 1)); partial responses were observed in 5 patients. Melphalan 180 mg/m2 and etoposide 3000 mg/m2 is a potent high-dose chemotherapy regimen with significant antineoplastic activity, particularly for breast cancer, and has acceptable toxicity when administered in conjunction with autologous BM re-infusion.
 ...
PMID:Phase I trial of high-dose melphalan, high-dose etoposide and autologous bone marrow re-infusion in solid tumors: an Eastern Cooperative Oncology Group (ECOG) study. 799 70

In small cell lung cancer, combination chemotherapy including agents such etoposide, teniposide, cisplatin, doxorubicin, ifosfamide, vincristine and cyclophosphamide continues to be the cornerstone of therapy. The importance of dose scheduling of etoposide with continuous treatment of 5 days' duration or more is becoming more and more clear. Complete or partial responses secondary to combination chemotherapy occur in 80-90% of all patients with median durations of 9 to 11 months. Median survival in these studies is unchanged, at present 11-16 months depending on the initial tumour stage. The optimum duration of treatment is still uncertain, but generally a period of 6 to 9 months is used. The use of G-CSF with combination chemotherapy leads to reductions in the incidence of fever, duration and severity of grade 4 neutropenia, and in the total number of days of treatment with i.v. antibiotics and days of hospitalization. No differences have been observed in response rates, duration of response or survival. Therapeutic results for epidermoid, cancer, adeno carcinoma, large cell carcinoma and mesothelioma are essentially unchanged. The treatment of patients with these tumours should continue to be considered experimental since no standard chemotherapy has as yet been developed, neither when given as single modality nor in combination with surgery or radiotherapy. Two studies published in 1991 comparing induction chemotherapy before irradiation versus irradiation alone have resulted in improvement of median and 2-year survival, while a third study did not show such an improvement. The fact remains that three-fourths of patients with local disease die within 3 years, and further improvements in both systemic and local treatment are needed.
 ...
PMID:Lung cancer. 831 12

The aim of this Phase II study was to test the feasibility of intensifying standard chemotherapy in the treatment of small cell lung cancer (SCLC) by reducing the interval between cycles from 3 to 2 weeks by adding recombinant human methionyl granulocyte colony-stimulating factor (G-CSF; filgrastim) to shorten the duration of neutropenia following each cycle. Thirty-two patients with SCLC were prescribed six cycles of 2-weekly doxorubicin 50 mg/m2 and cyclophosphamide 1 g/m2 on day 1, and etoposide 120 mg/m2 i.v. on days 1, 2 and 3 (ACE), plus filgrastim in a fixed dose of 300 micrograms s.c. on days 4-14 of each cycle. Three patients died during the treatment period and a further nine had chemotherapy terminated before the sixth cycle, all nine because of toxicity. All 32 patients have been followed up for at least 21 months; 14 (44%) were alive at 12 months and the median survival period was 356 days. Of the 127 intervals between cycles of chemotherapy, 74 (58%) were of the prescribed 14 days, 18 (14%) of 15-20 days, 25 (20%) of 21 days, and 10 (8%) were longer. The results were best during the first four cycles, during which 71% of the 83 intervals were of 14 days and a further 10% were less than 21 days. The main reason for delay was haematological toxicity in 37 of the 53 instances. Symptoms of myelosuppression occurred in 23 patients, but at 14 days after a cycle of chemotherapy, all 127 available neutrophil granulocyte counts were normal. Twenty-one patients received blood transfusion and five platelet transfusion. The only adverse effects attributed to filgastrim were episodes of rash, throat swelling, anorexia and shivering, affecting one patient. We conclude that the policy of adding filgrastim allows the dose intensity of ACE chemotherapy to be increased by reducing the intervals between cycles. The findings reinforce those of a parallel study involving lenograstim.
 ...
PMID:Increasing and planned dose intensity of doxorubicin, cyclophosphamide and etoposide (ACE) by adding recombinant human methionyl granulocyte colony-stimulating factor (G-CSF; filgrastim) in the treatment of small cell lung cancer (SCLC). Medical Research Council Lung Cancer Working Party. 858 54

Chemotherapy of small cell lung cancer is reviewed. Combination chemotherapy with cisplatin/etoposide (PE) or CAV (cyclophosphamide, adriamycin and vincristine) alternating with PE was established as standard regimens. Dose intensive chemotherapy, such as weekly regimens or using G-CSF, is being investigated. In patients with limited disease (LD), combined modality treatment is proven to produce favorable results, but the best sequence or fractionation of thoracic radiotherapy is unknown. More progress in the treatment of small cell lung cancer is expected.
 ...
PMID:[Chemotherapy of small cell lung cancer]. 875 97

The incidence of lung cancer is increasing, and therapy for patients with this disease is not satisfactory. Surgery is done for patients with clinical (c)-stage I, II, and resectable stage IIIA non-small cell lung cancer (NSCLC). Chemotherapy, alone or in combination with radiotherapy, is given to patients with unresectable stage IV and stage III NSCLC, respectively. Chemotherapy is an important therapeutic modality for patients with small cell lung cancer (SCLC). CDDP + VP-16 (PVP) and CPA + ADM + VCR (CAV) alternating PVP regimens are standard treatment for patients with SCLC. Chemotherapy and radiotherapy are given to patients with limited disease. To develop more effective treatments, we are investigating (1) the schedule and timing of radiotherapy, (2) combination chemotherapy including new drugs, (3) dose-intensive chemotherapy, and (4) new strategies such as gene therapy. Radiotherapy is commonly used sequentially and the standard fractionation is 2 Gy/fr/day. We are studying other timings, such as concurrent and alternating, and other schedules, such as hyperfractionation and accelerated hyperfractionation. Promising new drugs include paciltaxel, docetaxel, vinorelbine, and CPT-11. These are now used in combination with platinum. To evaluate dose-intensive chemotherapy for SCLC, we are conducting a phase III study comparing CODG + G-CSF with CAV/PVP.
 ...
PMID:[Can improvement in therapy decrease the rate of death due to lung cancer?]. 875 77

Standard meta-analytical and pharmacoeconomic techniques were used to study the clinical effectiveness and the cost-effectiveness ratio of the prophylactic (or pre-emptive) administration of G-CSF to patients with small cell lung cancer treated with conventional myelosuppressive cytotoxic chemotherapy. In the first part of our study, we conducted a meta-analysis of the randomized clinical trials evaluating G-CSF for this clinical indication. Three trials were identified by our literature search and were included in the meta-analysis (overall number of patients = 606). The end-points for evaluating G-CSF included mortality from infection and the cumulative incidence of neutropenic fever over six cycles of chemotherapy. The results of our meta-analysis demonstrate that prophylactic G-CSF did not affect mortality but significantly reduced the incidence of neutropenic fever from 68.3% to 38.7% (pooled odds ratio = 0.29, 95% CI: 0.21-0.40; P < 0.001). In the second part of our study, we carried out a pharmacoeconomic analysis to estimate the cost-effectiveness ratio of pre-emptive G-CSF (i.e. the 'average' cost associated with the prevention of an episode of neutropenic fever). This cost-effectiveness ratio was US$ 14,372 using the Italian price of the drug converted into dollars, or US$ 41 088 using the US price. Finally, we estimated the revenue-neutral price of G-CSF based on American data of the cost-of-illness. The price ranged from US$ 395 to US$ 569 per cycle, a figure higher than the value (US$ 150) previously reported in the literature.
 ...
PMID:G-CSF for the prophylaxis of neutropenic fever in patients with small cell lung cancer receiving myelosuppressive antineoplastic chemotherapy: meta-analysis and pharmacoeconomic evaluation. 880 40

Etoposide is a widely used cytotoxic agent with a broad spectrum of activity in human malignancies. This agent has been incorporated into many transplant regimens although toxicity occurs because of its poor water solubility and toxic excipients. Etoposide phosphate, a water soluble prodrug of etoposide, has been studied at conventional dosages in man and shown to have advantages over the parent compound. We have extended our previous experience with this new agent to evaluate the levels needed in transplantation protocols. This phase I study of intravenous high-dose etoposide phosphate over 2 h on days 1 and 2 was designed to determine whether or not dose linearity between the amount of etoposide phosphate administered to patients and generation of etoposide in vivo as seen with conventional dosages of this agent would be present at transplant-dose levels. In addition, the toxicities of these dose levels with the short infusion schedule were defined. A conservative dose escalation scheme was chosen based upon prior knowledge of etoposide. Thirty-one patients (19 male, 12 female) with CALGB performance status 0-1 with a variety of solid tumors entered this study. The patients were treated with dose levels of etoposide phosphate given as the etoposide-equivalent doses of 250, 500, 750, 1000, 1200, 1400, and 1600 mg/m2/day in 250-400 ml of normal saline given as an intravenous infusion over 2 h on days 1 and 2 every 28 days. After the maximal tolerated dose level was determined on this schedule, additional patients received etoposide phosphate as a 4 h infusion on both days in an attempt to reduce toxicities. G-CSF (5 micrograms/kg/day) was administered subcutaneously to all patients from day 3 until the WBC > or = 10000/microliters. Nonhematologic toxicity was considered to be dose limiting. Serial plasma samples for pharmacokinetics were obtained from patients on day 1 of cycle 1. For the 2 h infusion, the maximum tolerated dose of etoposide phosphate was 1000 mg/m2/day x 2 with dose limiting mucositis. In the small number of patients studied, the maximum tolerated dose was reached for the 4 h infusion at 1400 mg/m2/day of drug, again due to mucositis. Other toxicities, despite the rapid infusion schedule, were modest with transient mild headache being most common. At the highest doses etoposide phosphate was efficiently and rapidly dephosphorylated to etoposide. Etoposide generated by dephosphorylation of etoposide phosphate had plasma disposition curves characteristic of etoposide administered parenterally. One partial response occurred in a patient with small cell lung cancer. Etoposide phosphate can be rapidly infused in modest fluid volumes at dosages required for transplantation protocols with minimal acute side-effects. On a 2 h schedule, mucositis becomes the dose limiting nonhematologic toxicity. Mucositis seems to correlate with peak dose levels of the drug rather than total drug administered. On a 4 h infusion schedule given sequentially for 2 days, the maximum tolerated dosage could be increased 40% compared to the 2 h schedule. The relative ease of administration and the rapid conversion of this prodrug into etoposide should make it useful in high-dose therapy settings.
 ...
PMID:Phase I study of high-dose etoposide phosphate in man. 893 36

The present study was designed to investigate in vivo immunomodulatory properties of hematopoietic growth factors. The influence on the activation of cytokine synthesis and on the expression of surface antigens associated with cellular activation of G-CSF or GM-CSF was investigated in cancer patients receiving these factors. One single dose of growth factor was administered to patients with bladder cancer (G-CSF group) or small cell lung cancer (GM-CSF group) before chemotherapy. After cytoreductive chemotherapy patients received supportive therapy with G-CSF or GM-CSF. Peripheral blood mononuclear cells and plasma samples were obtained for flow cytometry, Northern blot analysis, and assessment of cytokine protein levels after single-dose as well as after continuous cytokine administration. Our results demonstrate differences in the induction of biological activities by GM-CSF and G-CSF in vivo which correlate well with in vitro findings. Among mature hematopoietic cells the effect of G-CSF is restricted to the granulocyte lineage. With GM-CSF moderate but unequivocal modulation of monocyte function was observed. On peripheral blood monocytes expression of MHC class-II molecules and CD44 was markedly stimulated. After one single dose of GM-CSF, plasma levels of sCD25 and IL-1RA were significantly induced (p < 0.0001, p = 0.032, respectively) and a trend to increased IL-8 levels was observed. The changes in plasma proteins were not correlated with shifts of mRNA expression for IL-8 and IL-1RA. T-cell activation was not observed with either cytokine. These results suggest that immunomodulatory features are differentially regulated by G-CSF and GM-CSF. The clinical relevance of a selective use of both hematopoietic growth factors in various disease settings remains to be determined.
 ...
PMID:Regulation of immunomodulatory functions by granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in vivo. 895 41

Hematopoietic growth factors are cytokines able to modulate proliferation and differentiation of bone marrow progenitors. We have reviewed the effectiveness of GM-CSF in protecting marrow from chemotherapy-induced neutropenia, mainly in the setting of cyclic polychemotherapy; in particular, studies employing low doses of GM-CSF have been considered. G-CSF or GM-CSF may be particularly useful in situations in which the likelihood of a clinically relevant neutropenia is high, both because of higher dose intensity (obtained by intensification of doses of each cycle or by shortening of intervals between cycles) or because of pretreatment patient characteristics (old age, poor performance status, previous extensive chemotherapy or radiotherapy, experience of neutropenia in the previous cycles). GM-CSF at the conventional dose of 5 micrograms/kg was utilized to increase the etoposide dose to 900 mg/m2 in a chemotherapy program including also carboplatin and ifosfamide in patients with small cell lung cancer. In a randomized study by Ardizzoni et al., the administration of GM-CSF at the dose of 10 micrograms/kg following CEF program (cyclophosphamide, epirubicin and fluorouracil) was effective in reducing from 20 to 16 days the time interval among cycles. Since there is a relationship between GM-CSF dose levels and toxicity, it is attractive to investigate whether GM-CSF at doses lower than 5 micrograms/kg retains its myeloprotective effects, with a substantial reduction in its toxic effects. Grem et al. have observed that 3 micrograms/kg GM-CSF may allow the administration of 425 mg/m2 fluorouracil for five days; Reed et al. demonstrated that 600 mg/m2 carboplatin may be safely administered if protection with 3 micrograms/kg GM-CSF is applied; Kehoe et al. achieved acceleration of cyclophosphamide-cisplatin combination by GM-CSF at the dose of 3 micrograms/kg. We conclude that low dose GM-CSF deserves further evaluation in order to determine effectiveness and potential applications in the clinical practice.
 ...
PMID:[Low-dose GM-CSF and dose intensity of antineoplastic agents]. 944 57


1 2 3 Next >>