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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-six patients with metastatic non-small-cell lung cancer (NSCLC) were treated with a combination of high-dose cisplatin, etoposide, and mitomycin. Thirty-four patients (74%) had a performance status of 1, and 39 patients (85%) had adenocarcinoma. Of the 42 patients evaluable for response and toxicity, four achieved a partial response (10%); no patient achieved a complete response. Seven patients who had received prior chemotherapy showed no major response. The median survival of all 42 patients was 23 weeks. Myelosuppression was the major dose-limiting toxicity for this regimen, and 12 of 46 patients (26%) developed neutropenic fever requiring hospitalization and parenteral antibiotics. Of the 12 patients with severe neutropenic fever, one patient died because of toxicity. Nonhematologic toxicities, including azotemia, peripheral neuropathy, nausea, vomiting, and hearing loss were transient and modest. We conclude that high-dose cisplatin combined with etoposide and mitomycin is a relatively toxic regimen with a low response rate. Further evaluation of the combination as given in this trial is not warranted.
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PMID:Phase II study of combination therapy with high-dose cisplatin, etoposide, and mitomycin in patients with advanced non-small-cell lung cancer. 131 94

The efficacy of combined high-dose etoposide with standard dose cisplatin was evaluated in patients who had refractory lung cancer after standard chemotherapy. Each patient was given etoposide at 500 mg/m2/day on day 1 to 3 continuously (total dose 1,500 mg/m2) and cisplatin at 80 mg/m2 on day 1. Fifteen patients (7 adenocarcinoma, 5 small cell lung cancer, 2 squamous cell lung cancer and 1 sarcoma, which latter was difficult to distinguish from giant cell carcinoma) were entered in this study. The overall response was 41.7% (5 of 12); five partial response, 6 no change, and 1 progressive disease. Three treatment-related deaths were observed; one resulted from sepsis and two from respiratory failure because of tumor progression. All of the patients developed severe myelosuppression; the mean nadir white blood cell count was 400, and the mean nadir platelet count was 24,000 in 28 evaluable courses. The range of maximum concentration of etoposide determined by HPLC was from 17.4 to 39.1 micrograms/ml. These results suggest that high-dose etoposide combined with a standard dose of cisplatin is effective against refractory lung cancer.
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PMID:[Pilot phase II trial of high-dose etoposide combined with cisplatin in the treatment of refractory lung cancer]. 131 97

Encouraging response rates have been observed with long-term daily administration of oral etoposide to treat lung cancer. Reasons why EP (etoposide/cisplatin) has been used to treat non-small cell lung cancer (NSCLC), despite the fact that etoposide has demonstrated only a modest degree of activity against this disease, are preclinical suggestions of cisplatin/etoposide synergism and successful results for the combination in treating small cell lung cancer (SCLC). We evaluated a long-term daily oral etoposide regimen in combination with cisplatin for NSCLC. One course consisted of cisplatin on day 1 and etoposide from day 1 through day 21. The course was repeated, beginning at day 29. We concluded that the maximum tolerated dose in this schedule was 50 mg/m2/day oral etoposide for 21 days plus 80 mg/m2 intravenous (i.v.) cisplatin on day 1. The major dose-limiting toxic effect was myelosuppression, and mucositis was also significant in some patients. During this phase I study of 22 patients (18 evaluable), we observed partial responses (PRs) in 4 patients, 1 each with uterine cancer and SCLC, and 2 with squamous cell lung cancers. We then designed a phase II pilot study in patients with advanced NSCLC. The recommended treatment schedule is 80 mg/m2 i.v. cisplatin on day 1 plus 40 mg/m2/day oral etoposide for 21 consecutive days. Of the 13 evaluable patients, PRs were observed in 4 (30.8%), in 2 patients with adenocarcinoma and 2 with squamous cell carcinoma. None of the side effects were severe or life-threatening. Nearly all of the projected doses were given, with delays of 7-10 days. In this pilot phase II study, the response rate of advanced NSCLC was above 30%. Future studies should combine long-term administration of oral etoposide with radiation therapy or surgery to treat stage III NSCLC.
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PMID:Platinum/oral etoposide therapy in non-small cell lung cancer. 132 14

A total of 49 patients with advanced, previously untreated non-small-cell lung cancer (NSCLC) were treated with a new antifolate, Edatrexate (10-ethyl-10-deaza-aminopterin; 10-EdAM). Patients received 80 mg/m2 weekly for 12 weeks, and responders received a further 6 cycles at 2-week intervals. Dose reductions were carried out for haematological toxicity and mucositis. Response was assessed prior to each treatment according to WHO criteria. Among the 45 evaluable patients, 6 [13.3%; 95% confidence interval (CI), 6%-26%] achieved a partial response (PR) and 9 (20%; 95% CI, 11%-34%) showed a minor response (MR; 25%-50% reduction in the sum of 2 perpendicular tumour diameters). In those receiving four or more cycles of treatment, the PR and MR rates were 17.6% and 26.4%, respectively. The resultant toxicity mainly constituted skin rash, mucositis and myelosuppression. Edatrexate is active against NSCLC and produces toxicity profile similar to that of methotrexate.
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PMID:Phase II study of Edatrexate in stage III and IV non-small-cell lung cancer. 132 68

The efficacy and toxicity of two regimens based on etoposide/carboplatin with or without cyclophosphamide/vincristine in the management of small cell lung cancer (SCLC) were assessed by the Australian Lung Cancer Study Group. Response rates of 77% and 85% were noted for the two- and four-drug regimens, respectively, among patients with limited disease (LD). Response rates among patients with extensive disease (ED) were 58% and 79%, respectively. The profiles of nonhematologic toxicity were modest; myelosuppression was dose-limiting when colony-stimulating factors were not used. Twenty-six patients (14%) were older than 70 years of age. Although hematologic toxicity was more severe in the elderly group, there was no significant difference in nonhematologic toxicity, response rate, or overall survival between the geriatric and younger groups. When LD only was considered, 33% of those younger than 70 were alive at 2 years; no patients aged 70 years or older with LD were alive beyond 2 years. In patients with ED, there was no age-related difference in survival. Cytotoxic regimens based on etoposide/carboplatin constitute useful treatment for SCLC, with high response rates and manageable toxicity, irrespective of patient age.
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PMID:Carboplatin-containing regimens for small cell lung cancer: implications for management in the elderly. 132 17

Gemcitabine (dFdC) and DMDC are new antimetabolites with good antitumor activities against various tumors which include human leukemic cell lines and a number of rodent and human solid tumors and human tumor. They are structurally related to cytarabine (Ara-C) which is known as one of the most effective drugs against adult acute leukemia, but many solid tumors are insensitive not been found to the drug. Gemcitabine acts as an inhibitor of ribonucleoside diphosphate reductase and inhibits DNA synthesis. Biochemically Gemcitabine is rapidly phosphorylated to dFdCTP which has a comparatively longer half-life than that of Ara-C, showing a therapeutic activity against tumors. In the phase I trials, the reported maximum-tolerated doses were 790 mg/m2 to 1370 mg/m2 at the schedule of 30 minutes i.v. infusion once a week for three weeks but higher dose levels (2,500 mg/m2 to 4,800 mg/m2) were reported in the schedule of prolongation of the infusion time. Reported toxicities were myelosuppression, fatigability, fever, appetite loss and skin rash. Toxicities were seemed to be mild. In USA, Europe and South Africa, phase II trials of Gemcitabine at the schedule of 30 minutes infusion once a week for three weeks followed by one week rest were performed against solid tumors (breast cancer, ovarian cancer, renal cancer, colorectal cancer, pancreas cancer, head and neck cancer, and lung cancer) and showed good responses to those tumors. DMDC was developed in Japan, and a phase I trial is currently on-going.
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PMID:[New antitumor antimetabolites--gemcitabine and DMDC]. 133 22

The purpose of this study was to evaluate the toxicity and response efficacy of fixed-dose oral ifosfamide (OI)-mesna (M) in advanced, non-small-cell lung cancer (NSCLC). OI was given in four different fractionated-dose treatment schedules with a total dose per cycle of either 3.0 g/m2, 6.0 g/m2, 7.5 g/m2 or 10 g/m2 (equivalent to a daily dose of either 750 mg, 1000 mg or 1250 mg.) M was given p.o. by drinking ampules. In the 64 patients (pts) included, a total of 305 treatment cycles were administered with no evidence of severe neurotoxicity. Twenty-two pts (37%) developed mild to moderate CNS toxicity. Neither myelosuppression, alopecia, gastrointestinal toxicity nor urotoxicity were clinical problems. On schedule 2 (6 g/m2), 3 of 14 evaluable pts (21%) had partial remissions (PR), and on schedule 3 (7.5 g/m2) 4 pts (25%) showed PRs. The median duration of response was 9 months (mts) for pts on schedule 2, and 8 mts for pts on schedule 3. We conclude that OIM can easily be tolerated in the same dose usually given intravenously (7.5 g/m2/mts), when patients at high risk for developing CNS toxicity have been previously excluded from therapy. In order to reduce CNS toxicity, it is suggested that the total dose per cycle should not exceed 7.5 g/m2 (1000 mg daily) within a fractionated-dose, 14-day treatment schedule. We further conclude that the tumor response efficacy of OIM in NSCLC is comparable to the one achieved by intravenously-administered IM, whereby the total monthly OI dose should not be less than 6.0 g/m2 (750 mg daily).
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PMID:Oral ifosfamide-mesna: a clinical investigation in advanced non-small-cell lung cancer. 133 66

The study was aimed to evaluate the feasibility of dose-intensive chemotherapy given on a weekly basis for 12 weeks. Seventeen [7 with limited disease (LD) and 10 with extensive disease (ED)] previously untreated patients with small-cell lung cancer (SCLC) were treated with the cisplatin, vincristine, doxorubicin, and etoposide (CODE) regimen. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was given to eight patients for the purpose of increasing the dose intensity. Overall response rate was 88%, with a 29% complete response. The median survival times were greater than 20.5 months for LD patients and 8.1 months for ED patients. Overall actual dose intensity was 88% of planned protocol. The major toxicity was myelosuppression. Fifteen patients (88%) had grade 3 or 4 leukopenia. Other problems were weight loss and worsening of performance status during the treatment. RhG-CSF significantly reduced leukopenic nadirs and shortened the neutropenic period. Our preliminary results indicate that 12 cycles of the CODE regimen on a weekly schedule is effective for SCLC, but is also associated with significant toxicity.
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PMID:Weekly dose-intensive chemotherapy in patients with small-cell lung cancer: a pilot study. 137 63

Etoposide, a podophyllotoxin derivative, has demonstrated antitumor efficacy in a number of human malignancies, including lymphomas, germinal tumors, and lung cancer (especially small cell). Etoposide's antineoplastic activity is achieved through DNA strand breakage, which likely results from the formation of a complex involving drug, DNA, and the DNA unwinding enzyme, topoisomerase II. The drug's steady state volume of distribution ranges from 5 to 17 L/m2, and it is highly bound to plasma protein with an average free plasma fraction of 6%. A number of etoposide metabolites have been confirmed or postulated. Several cell lines have been shown to acquire resistance to etoposide through membrane transport changes. Considerable intrapatient variability exists in pharmacokinetic parameters following intravenous (IV) and oral dosing. Approximately 30% to 40% of unchanged IV drug is excreted in the urine, whereas biliary excretion appears a minor route of drug elimination. The bioavailability of oral etoposide averages 50%, although wide variability exists both among and within different patients. Bioavailability decreases as the dose of oral etoposide is increased. Several recent studies have attempted to correlate etoposide plasma concentrations with toxicity (primarily myelosuppression) in hopes of using this information to optimize drug dosing.
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PMID:Etoposide pharmacology. 149 25

The effects of chemotherapy on the growth of colony forming unit-granulocyte macrophage (CFU-GM) from the bone marrow (BM) and peripheral blood (PB) of 8 patients with lung cancer were studied by using recombinant interleukin-3, granulocyte macrophage-colony stimulating factor, and granulocyte-colony stimulating factor. After chemotherapy, the kinetics of CFU-GM depend on the type of chemotherapeutic regimens used: a rebound overshoot of CFU-GM in the PB was seen in the 4 patients treated with cisplatin plus etoposide (PVP) but not in the 4 patients treated with cisplatin plus mitomycin plus vindesine (CMV). In the BM, the recovery of CFU-GM was more retarded in patients treated with CMV relative to that seen in patients treated with PVP. The results obtained in simultaneous cultures revealed the differences between CMV and PVP in the kinetics of chemotherapy-induced myelosuppression. Determination of the optimal timing of in vivo use of hematopoietic growth factors after cytoreductive chemotherapy requires careful experimental design.
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PMID:Effect of chemotherapy on colony-forming unit-granulocyte macrophage from bone marrow and peripheral blood in patients with lung cancer. 154 93


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