Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A single-institution phase II study indicated that combination chemotherapy using UFT (tegafur and uracil) plus cisplatin (Platinol) in patients with non-small-cell lung cancer was active with less host toxicity than other cisplatin-based therapies. To confirm these observations, the Japan JFT Lung Cancer Study Group conducted a multi-institutional phase II trial. The number of patients planned for this trial is 110. Eligibility includes previously untreated stage IIIB or IV non-small-cell lung cancer and a good performance status. UFT 400 mg/m2 in two divided doses is administered orally on days 1 through 14, and cisplatin 80 mg/m2 is injected IV on day 8. This treatment is repeated every 3 or 4 weeks. Between April 1995 and May 1996, 67 patients were enrolled, and all 67 were considered eligible for an interim analysis performed in October 1996. Among 63 patients evaluable for response, there was an overall response rate of 30% (95% confidence interval, 19% to 41%), with one complete response and 18 partial responses. With a median follow-up duration of 44 weeks, the median survival time was 32 weeks and the 1-year survival rate was 25%. Grade 3 leukopenia occurred in only 1 of 67 patients (1.5%), and there was no thrombocytopenia of grade 3 or greater. Vomiting, the most common nonhematologic toxicity observed, reached grade 3 or 4 in only 6 patients (9%). This interim analysis seems to support the observations of the previous single-institution phase II trial.
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PMID:UFT plus cisplatin in advanced non-small-cell lung cancer: interim analysis of 67 patients. 934 79

Combined use of 5-fluorouracil (5-FU) and cisplatin has proven to have synergistic effects in many experimental systems and clinical studies. UFT, an oral preparation of uracil and tegafur in a 4:1 molar ratio, was reported to have enhanced activity as compared with 5-FU or tegafur alone against various human tumors. Based on those results, we conducted a pilot study to confirm the feasibility and antitumor effect of UFT in combination with cisplatin in patients with advanced non-small cell lung cancer (NSCLC). UFT was orally administered at a dose of 400 mg/m2 according to a protocol for step-wise prolongation of the administration period, such as days 1-14 in step I, days 1-21 in step II, days 1-28 in step III. During to course, cisplatin was administered at a fixed dose of 20 mg/m2/day on days 8 through 12. The course was repeated every 4 weeks. Numbers of patients enrolled in steps I, II, III were six, ten and six (a total of 22), respectively. There were three females and 19 males, PS scored 0/1/2 = 7/14/1, stage IIIA/IIIB/IV = 3/8/11. Adenocarcinoma/squamous cell carcinoma/large cell carcinoma = 11/7/4, and median age 68 (range 52-79). All 22 patients were evaluable for toxicity, and 21 for efficacy. Compliance of UFT declined as the administration period of UFT was prolonged. In step I, one patient had grade 3 toxicity of each neutropenia, thrombocytopenia, nausea/vomiting and diarrhea. In step II, grade 3, 4 neutropenia was seen in four patients, grade 3 thrombocytopenia and anorexia in one patient, and grade 3 nausea/vomiting in four patients. In step III, there was grade 3 neutropenia in two patients and grade 3 anorexia in one patient. All other toxicities were mild. The overall response rate was 38% (one CR and 7 PR, 95% C.I.: 21-59%). Combination therapy with oral UFT and 5-day infusion of cisplatin is feasible with substantial antitumor effect against advanced NSCLC. Since UFT compliance decreased in step III (no patient in step III received > 2 courses of treatment), we considered the step II schedule to be worth for further evaluation in a combination phase II study.
Lung Cancer 1997 Nov
PMID:Pilot study of UFT combined with 5 consecutive days cisplatin in non-small cell lung cancer. 944 49

The current study was designed to investigate direct inhibitory effects of N-acetyl-glucosaminyl-muramyldipeptide (GMDP) over the cytotoxic nature of TNF-alpha. A lactate dehydrogenase (LDH) assay of the inhibition of TNF-alpha cytotoxicity was done in vitro on the following cell lines: A549 (human lung carcinoma cells), A431 (human breast cancer cells) and L929 (mouse breast cancer cells). In a double-blind placebo-controlled trial, cancer patients with an elevated activity of all five LDH isoensymes were randomized to receive either a GMDP solution or a placebo; 63 patients were evaluated every third day for the mean daily number of episodes of nausea or vomiting, changes in clinical status, cell blood count and blood chemistry. A 95% inhibition of LDH release was noticed on A549 cells. Other cell lines were less sensitive to GMDP, with an observed 72% dose-dependent reduction in LDH activity. In vivo, LDH activity was decreased by 41% (+/-4%) (mean+/-SD) in all 21 subjects who were given 0.5-1.0 mg of GMDP daily. A lowering of LDH activity by 73.4% (+/-4%) was observed in 23 patients who received GMDP at a dosage of 1.5mg/kg daily. Correspondingly, a 10% (+/-2%) increase in LDH activity was noticed in 19 patients who were given a placebo (P < 0.01). During the follow-up period, the overall clinical condition of all patients treated with GMDP was improved. No side effects were observed. In nine patients who experienced nausea from tumor toxicity before treatment, the symptom subsided. In parallel, an extremely beneficial effect on lipids metabolism was noticed in all patients with elevated cholesterol and trigliceride levels. A dietary supplementation of GMDP has been shown to reduce systemic TNF-alpha cytotoxicity during tumor shock.
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PMID:Inhibition of systemic TNF-alpha cytotoxicity in cancer patients by D-peptidoglycan. 964 29

Three separate phase III randomized studies were conducted to compare the efficacy of a gemcitabine plus cisplatin combination (GC) with other chemotherapy regimens in the treatment of European and North American patients with inoperable (stage IIIB or IV) non-small cell lung cancer (NSCLC). The Spanish Lung Cancer Group (SLCG) compared the GC regimen with an etoposide plus cisplatin combination (EP), the Hoosier Oncology Group (HOG) compared it with single-agent cisplatin, and the Italian Lung Cancer Project (ILCP) compared it with a mitomycin plus ifosfamide plus cisplatin combination (MIC). The three studies each had a different primary objective (response rate, survival, or quality of life, respectively). From July 1995 to February 1997, 751 patients were enrolled into the three studies. In the SLCG study, 69 were entered in the GC arm and 64 in the EP arm; in the HOG study, 155 were entered in the GC arm and 154 in the cisplatin-alone arm; and in the ILCP study, 154 were entered in the GC arm and 152 in the MIC arm. In the SLCG study, gemcitabine 1,250 mg/m2 was given by 30-minute infusion on days 1 and 8 of each 21-day cycle. In the HOG and ILCP studies, gemcitabine 1,000 mg/m2 was given on days 1, 8, and 15 of each 28-day cycle. Cisplatin 100 mg/m2 was given on day 1 in the SLCG and HOG studies and on day 2 in the ILCP study. In the EP arm, etoposide 100 mg/m2 was given on days 1, 2, and 3 of each 21-day cycle. In the MIC arm, mitomycin 6 mg/m2 and ifosfamide 3 g/m2 were given on day 1 of each 28-day cycle. In the SLCG study, 28 patients (40.6%) in the GC arm and 14 patients (21.2%) in the EP arm achieved an objective response (P = .01). In the HOG study, 48 patients (31%) in the GC arm and 14 patients (9.1%) in the cisplatin-alone arm attained on objective response (P < .001). In the ILCP study, 61 patients (40%) in the GC arm and 42 patients (28%) in the MIC arm achieved an objective response (P = .03). Progression-free time was significantly longer for the GC arm (6.8 months) than for the cisplatin-alone arm (4.2 months) (P < .001). The median survival time was remarkably identical for the GC arms in the three studies (8.7 months), whereas it was 7.2 months for the EP arm, 7.6 months for the cisplatin-alone arm, and 9.5 months for the MIC arm. The main toxicities were myelosuppression and vomiting. The assessment of quality of life in the ILCP study is ongoing. Both 21- and 28-day cycles of GC were effective in the treatment of NSCLC, and this combination can be considered as a current "standard" therapy for advanced NSCLC patients.
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PMID:The activity of gemcitabine plus cisplatin in randomized trials in untreated patients with advanced non-small cell lung cancer. 972 82

A total of 30 with good prognosis small cell lung cancer were treated with a modified 'ICE' (ifosfamide, carboplatin and etoposide) chemotherapy regimen in an attempt to achieve a high response rate with less toxicity than is seen with the full 'ICE' regimen. This was given every 4 weeks for a maximum of six cycles. In total 25 patients (83%, 95% CI (70-97%)) experienced a partial or complete response at some stage of their treatment. Of these patients, 12 (40%, 95% CI (22-58%)) showed a complete response. A total of 19 patients (63%) had to have their dose reduced and/or delayed at some point due to toxicity. Nadir blood counts showed that 19 patients (63%, 95% CI (46-81%)) had WHO grade 3 or 4 thrombocytopenia, and 24 (86%, 95% CI (73-99%)) had grade 3 or 4 neutropenia. A total of 17 patients (53%) completed six cycles of chemotherapy. In total 3 patients died during treatment all due to treatment-related complications. Median survival was 12.6 months (95% CI (11.6, 14.7 months)). Nausea, vomiting, dysphagia, activity, mood and overall condition, as recorded using daily diary cards, were worse at the beginning of each chemotherapy cycle. Both response rates and survival were clinically acceptable. However, neutropenia and thrombocytopenia, although reduced from rates reported with the full ICE regimen, were still high. A prospective randomised controlled trial is now needed to assess this regimen in more detail.
Lung Cancer 1998 Aug
PMID:Modified ice study: a phase II study of an intensive, modified ICE regimen (ifosfamide, carboplatin and etoposide) in patients with better prognosis, small cell lung cancer. 982 45

We conducted a randomized phase II trial of two different schedules of topotecan in patients with advanced-stage non small lung cancer (NSCLC) without prior cytotoxic chemotherapy. All patients had histologic or cytologic confirmation of stage IV (M1) or III-B NSCLC. Patients were stratified by performance status, stage and weight loss. Patients were randomized to receive topotecan at intravenous doses of 1.5 mg/m(2)/day over 30 min for 5 days every 3 weeks (Arm A) or 1.3 mg/m(2)grade 3 in both arms included leukopenia, thrombocytopenia, malaise, constipation, diarrhea, lethargy, pulmonary, vomiting, infection and myalgia. Severe (> or = grade 3) thrombocytopenia occurred in 15.8% of Arm A patients and 37.8% of Arm B patients and this difference was statistically significant (P=0.03). The median times to progression are 101 and 63 days (P=0. 75) and the median survival times are 257 and 179 days (P=0.83) for Arms A and B, respectively. These differences in time to progression and overall survival are not statistically significant. Topotecan has limited, single agent activity in advanced NSCLC when given as 1. 5 mg/m(2)/day over 30 min for 5 days every 3 weeks. We do not intend to pursue further investigations with topotecan in patients with NSCLC.
Lung Cancer 2000 May
PMID:A randomized phase II trial of two schedules of topotecan for the treatment of advanced stage non-small cell lung cancer. 1071 33

A 66-yr-old man with a history of squamous cell carcinoma and small cell carcinoma of the lung presented with nausea, vomiting, and abdominal pain. After passing black stools, he underwent upper endoscopy which showed gastric ulceration. A gastric brushing was performed which showed numerous nonseptate, ribbon-like hyphae with right-angle branching. The cytologic features permitted a diagnosis of a zygomycotic infection which was confirmed by histologic examination. Despite appropriate antifungal therapy, the patient expired. To the best of our knowledge, this is the first case of gastric zygomycosis diagnosed by brushing cytology. We believe that gastric brushing cytology allows for rapid diagnosis of zygomycotic mycoses, due to the distinctive morphology of these organisms; however, histologic examination is still required for assessment of invasion.
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PMID:Gastric zygomycosis diagnosed by brushing cytology. 1090 34

The randomized clinical trial, LU19, conducted by the Medical Research Council Lung Cancer Working Party, was designed to compare ACE (doxorubicin, cyclophosphamide and etoposide) chemotherapy plus G-CSF (granulocyte colony-stimulating factor) at 2-week intervals versus ACE chemotherapy alone at standard 3-week intervals in patients with small-cell lung cancer. This trial investigated whether more intensive administration of ACE would improve overall survival and affect the quality of life of patients. The report on overall survival and other outcome measures will be published in the Journal of Clinical Oncology. In this paper we focus on methods of analysing aspects of data reflecting quality of life. Twelve symptoms of lung cancer and its treatment - cough, haemoptysis, pain, nausea, vomiting, hoarse voice, sore mouth, rash, lethargy, lack of appetite, alopecia, and dysphagia - were scheduled to be assessed on seven occasions for the ACE arm and on eight occasions for the ACE+G-CSF arm by clinicians during the first 18 weeks of the treatment period. However, in practice the number of assessment forms completed per patient ranged from 1 to 9, and assessment time-points were very different from those planned. These 'messy' longitudinal data are explored by both a summary measure approach, in which experience of a symptom is summarized by a single value, and an extensive model-based statistical approach, which explicitly takes into account correlation within repeated measures. These analyses provide a clear picture of symptom comparisons between the two treatments. The application of various methods offers not only an approach to assessing the robustness of the results but also a basis for investigating reasons for inconsistency of results across methods. We conclude that except lethargy, which is worse in the ACE+G-CSF arm, all symptoms are similar across the two arms during the treatment period.
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PMID:Analysis of messy longitudinal data from a randomized clinical trial. MRC Lung Cancer Working Party. 1098 40

The anthracenedione analogue, BBR 2778 is an active antitumour agent preclinically and has reduced potential for cardiotoxicity compared with other similar drugs in preclinical models. BBR 2778 was administered 3 weekly by a 1 h intravenous (i.v.) infusion to 24 patients and the dose escalated rapidly from 20 to 240 mg/m2. The dose-limiting toxicity (DLT) was neutropenia, common toxicity criteria (CTC) grade 4 in 3/5 patients at 240 mg/m2. Other toxicities > or = CTC grade 3 were: vomiting, lymphopenia, thrombocytopenia and lethargy. Blue discoloration of veins and urine was also noted. In 1 patient (120 mg/m2, four cycles) left ventricular ejection reaction (LVEF) fell (CTC grade 2) but with no clinical sequelae. BBR 2778 plasma pharmacokinetics were biphasic (mean t(1/2) at 180 mg/m2 = 14.1 h) and the urinary elimination of the unchanged drug was < 10%. In a patient with previously treated small cell lung carcinoma (SCLC), a 49% reduction in measurable disease was noted with resolution of pericardial and pleural effusions (120 mg/m2 x eight cycles). From the results of this phase I study a dose of 180 mg/m2 as a 1 h infusion every 3 weeks would be recommended for phase II trials.
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PMID:A clinical phase I and pharmacokinetic study of BBR 2778, a novel anthracenedione analogue, administered intravenously, 3 weekly. 1109 9

In a multicenter phase II Italian trial that used a 28-day dosing schedule of gemcitabine on days 1, 8, and 15 and cisplatin on day 2, thrombocytopenia and neutropenia were the main dose-limiting toxicities observed. The aim of the present study was to determine whether using 15-day cisplatin in lieu of the standard 2-day schedule in combination with weekly gemcitabine would decrease expected myelotoxicities, particularly thrombocytopenia. Fifty-one patients with advanced non-small cell lung cancer (NSCLC), a median age of 62 years (range 31-76) and baseline Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1, were enrolled. Twenty-four patients had stage IIIA-B disease and 27 had stage IV. Patients received gemcitabine 1000 mg/m(2) on days 1, 8, 15, and cisplatin 100 mg/m(2) on day-15, every 28 days for a total of 151 cycles. All patients were evaluable for toxicity. Grades 3 and 4 thrombocytopenia was observed in 16% of patients, grades 3 and 4 neutropenia in 35% of patients, and grade 3 anemia in 4% of patients (no grade 4 anemia). Nonhematologic toxicity was mild. Two patients had grade 3 vomiting, and another had grade 4 hepatic toxicity only after gemcitabine administration. The dose intensity of gemcitabine and cisplatin was well maintained. Of the 45 patients evaluable for response, there were 22 (49%) partial responders, 7 (15.5%) minimal responders, 9 (20%) with stable disease, and 7 (15.5%) progressions. Compared with the schedule used in a multicenter phase II Italian trial (day 2 cisplatin), day-15 cisplatin decreases incidences of thrombocytopenia (16 vs. 52%) and anemia (4 vs. 25%); the occurrence of neutropenia is similar (35 vs. 36%). Response rates are also similar (49 vs. 54%).
Lung Cancer
PMID:Decreased myelotoxicity of gemcitabine and cisplatin in advanced non-small cell lung cancer (NSCLC) with cisplatin infusion on day 15. 1116 7


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