The effectiveness of combined treatment with methylprednisolone and cyclophosphamide in oral paraquat poisoning. A prospective clinical trial of pulse therapy with glucocorticoid and cyclophosphamide in moderate to severe paraquat-poisoned patients. Repeated pulse of methylprednisolone and cyclophosphamide with continuous dexamethasone therapy for patients with severe paraquat poisoning. A pilot study of the effect of inhaled buffered reduced glutathione on the clinical status of patients with cystic fibrosis. The effects of the inhaled corticosteroid budesonide on lung function and bronchial hyperresponsiveness in adult patients with cystic fibrosis. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. Pilot study to assess the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis.
Paraquat is a bipyridil herbicide and in appropriate and careful usage, will not be health threatening. Most adult cases of intoxication are due to suicidal attempts rather than accidental exposure. Therapeutic response has been reported to be appropriate with high doses of cyclophosphamide and glucocorticoids and survival is reported to be approximately 75%. So, this study was designed to evaluate the effects of combined treatment with cyclophosphamide and glucocorticoids in patients with paraquat poisoning.
                During a two-year period 45 patients with paraquat poisoning were admitted to Sina Hospital, Hamadan, Iran, of whom 20 had moderate to severe intoxication. Eleven patients (group 1) received conventional treatment and nine patients (group 2) received conventional treatment plus intravenous infusions of cyclophosphamide 15 mg/kg daily for two days, methylprednisolone one gram daily for three days, and mesna 15 mg/kg for four days.
                The mean age+/-SD in group 1 was 25+/-10 years and in group 2 was 26+/-10 years. In group 1 three patients were females and eight patients were males. In group 2 one patient was female and eight patients were males. There were no differences between the groups in the time elapsed from ingestion to presentation at hospital or in the beginning of hemodialysis. The mortality rate in group 1 was 81.8% and in group 2 was 33.3% (P< 0.05). All fatalities caused by acute respiratory distress syndrome.
                Pulse therapy with cyclophosphamide and methylprednisolone may be effective in preventing respiratory failure and reducing mortality in patients with moderate to severe paraquat poisoning. nan Paraquat is widely used in the world, and all treatments for paraquat poisoning have been unsuccessful. Many patients have died of paraquat poisoning in developing countries. A novel anti-inflammation method was developed to treat severe paraquat-poisoned patients with >50% to <90% predictive mortality: initial pulse therapy with methylprednisolone (1 g/day for 3 days) and cyclophosphamide (15 mg/kg/day for 2 days), followed by dexamethasone 20 mg/day until Pao2 was >11.5 kPa (80 mm Hg) and repeated pulse therapy with methylprednisolone (1 g/day for 3 days) and cyclophosphamide (15 mg/kg/day for 1 day), which was repeated if Pao2 was <8.64 kPa (60 mm Hg).
                Randomized controlled trial.
                Academic medical center in Taiwan.
                Twenty-three paraquat-poisoned patients with >50% and <90% predictive mortality assessed by plasma paraquat levels were prospectively and randomly assigned to the control and study groups at a proportion of 1:2.
                The control group received conventional therapy and the study group received the novel repeated pulse treatment with long-term steroid therapy.
                We measured patient mortality during the study period. There was not a different distribution of basal variables between the two study groups. The mortality rate (85.7%, six of seven) of the control group was higher than that of the study group (31.3%, five of 16; p = .0272).
                The novel anti-inflammatory therapy reduces the mortality rate for patients with severe paraquat poisoning. To assess the impact of inhaled, buffered reduced glutathione (GSH) on clinical indicators of cystic fibrosis (CF) pathophysiology.
                A randomized, double-blind, placebo-controlled pilot study was conducted over an 8-week period. Nineteen subjects, age 6 to 19 years, with CF status documented by positive sweat chloride test results (> 60 mEq/L) were recruited for the trial. After matching on age and sex, 10 patients were randomly assigned to the treatment group and 9 patients to the placebo group. Primary outcomes were FEV1, FVC, forced expiratory flow at 25 to 75% of vital capacity, and peak flow; secondary outcomes were body mass index, 6-min walk distance, and self-reported cough frequency, mucus production/viscosity/color, wellness, improvement, and stamina. INTERVENTIONS AND ANALYSIS: Treatment was buffered GSH, and placebo was sodium chloride with a hint of quinine. The total daily dose of buffered GSH was approximately 66 mg/kg of body weight, and the total daily dose of placebo was approximately 15 mg/kg of body weight (quinine, 25 to 30 microg/kg). Doses were distributed across four inhalation sessions per day and spaced 3- to 4-h apart. General linear mixed models were used to analyze the data. The final sample size was nine subjects in the treatment group and seven subjects in the placebo group.
                Mean change for peak flow was -6.5 L/min for the placebo group and +33.7 L/min for the GSH group (p = 0.04), and self-reported average improvement on a scale from 1 to 5 (1 being much worse and 5 being much better) was 2.8 for placebo and 4.7 for GSH (p = 0.004). Of the 13 primary and secondary outcomes examined, 11 outcomes favored the treatment group over the placebo group (p = 0.002), indicating a general tendency of improvement in the GSH group. No adverse events in the treatment group were noted.
                This pilot study indicates the promise of nebulized buffered GSH to ameliorate CF disease, and longer, larger, and improved studies of inhaled GSH are warranted. Bronchial hyperresponsiveness is present in 40-60% of adult patients with cystic fibrosis (CF). Drugs which alter airway hyperresponsiveness have not yet been studied in CF. In this randomized placebo-controlled study, we investigated the effects of an inhaled corticosteroid, budesonide, on lung function and bronchial hyperresponsiveness in adult CF patients, with proven bronchial hyperresponsiveness to histamine. Twelve patients were treated with budesonide, 1600 micrograms day-1, and with placebo during two periods of 6 weeks in a randomized, double-blind, cross-over study. Drug effects were assessed with regard to bronchial hyperresponsiveness to histamine, spirometry and clinical symptom scores. After treatment with budesonide, no significant differences in spirometry were seen, however, bronchial hyperresponsiveness to histamine significantly improved as compared to baseline. Fifty-eight percent of the patients showed at least one doubling-dose increase in PC20 histamine. Daily symptom scores showed small, but statistically significant, improvements in dyspnoea and cough after budesonide treatment. There is increasing evidence suggesting that excessive inflammatory responses contribute to the pulmonary damage that characterizes CF. Treatment with oral corticosteroids improved the clinical course of selected CF patients, but was associated with unacceptable adverse effects. We conclude that daily inhalation of 1600 micrograms day-1 budesonide for 6 weeks induced a small, but significant, improvement in bronchial hyperresponsiveness to histamine, and symptoms of cough and dyspnoea in adult CF patients. Longer observations are needed to establish whether inhaled corticosteroids improve the long term outcome of CF. To evaluate the benefits and the drawbacks of post-operative radiotherapy in completely resected Stage I (a and b) non-small cell lung cancer (NSCLC).
                Patients with pathological Stages Ia and Ib NSCLC have been randomized into two groups: Group 1 (G1) received adjuvant radiotherapy, Group 0 (G0) the control group did not receive any adjuvant therapy. Local control, toxicity and survival have been evaluated.
                Between July 1989 and June 1997, 104 patients with pathological stage I NSCLC have been enrolled in this study. Fifty-one patients were randomized to G1 and 53 to G0. Six patients have been excluded from the study due to incomplete follow-up data. Regarding local control, one patient in the G1 group had a local recurrence (2.2%) while in the G0 12 local recurrences have been observed (23%). Seventy-one percent of patients are disease-free at 5 years in G1 and 60% in G0 (P=0.039). Overall 5-year survival (Kaplan-Meier) showed a positive trend in the treated group: 67 versus 58% (P=0.048). Regarding toxicity in G1, six patients experienced a grade 1 acute toxicity. Radiological evidence of long-term lung toxicity, with no significant impairment of the respiratory function, has been detected in 18 of the 19 patients who have been diagnosed as having a post-radiation lung fibrosis.
                Adjuvant radiotherapy gave good results in terms of local control in patients with completely resected NSCLC with pathological Stage I. Overall 5-year survival and disease-free survival showed a promising trend. Treatment-related toxicity is acceptable. To demonstrate the efficacy of radiochemotherapy (RCT) as the first choice of treatment for advanced unresectable head-and-neck cancer. To prove an expected benefit of simultaneously given chemotherapy, a two-arm randomized study with hyperfractionated accelerated radiochemotherapy (HF-ACC-RCT) vs. hyperfractionated accelerated radiotherapy (HF-ACC-RT) was initiated. The primary endpoint was 1-year survival with local control (SLC).
                Patients with Stage III and IV (UICC) unresectable oro- and hypopharyngeal carcinomas were randomized for HF-ACC-RCT with 2 cycles of 5-FU (600 mg/m(2)/day)/carboplatinum (70 mg/m(2)) on days 1--5 and 29--33 (arm A) or HF-ACC-RT alone (arm B). In both arms, there was a second randomization for testing the effect of prophylactically given G-CSF (263 microg, days 15--19) on mucosal toxicity. Total RT dose in both arms was 69.9 Gy in 38 days, with a concomitant boost regimen (weeks 1--3: 1.8 Gy/day, weeks 4 and 5: b.i.d. RT with 1.8 Gy/1.5 Gy). Between July 1995 and May 1999, 263 patients were randomized (median age 56 years; 96% Stage IV tumors, 4% Stage III tumors).
                This analysis is based on 240 patients: 113 patients with RCT and 127 patients with RT, qualified for protocol and starting treatment. There were 178 oropharyngeal and 62 hypopharyngeal carcinomas. Treatment was tolerable in both arms, with a higher mucosal toxicity after RCT. Restaging showed comparable nonsignificant different CR + PR rates of 92.4% after RCT and 87.9% after RT (p = 0.29). After a median observed time of 22.3 months, l- and 2-year local-regional control (LRC) rates were 69% and 51% after RCT and 58% and 45% after RT (p = 0.14). There was a significantly better 1-year SLC after RCT (58%) compared with RT (44%, p = 0.05). Patients with oropharyngeal carcinomas showed significantly better SLC after RCT (60%) vs. RT (40%, p = 0.01); the smaller group of hypopharyngeal carcinomas had no statistical benefit of RCT (p = 0.84). For both tumor locations, prophylactically given G-CSF was a poor prognostic factor (Cox regression), and resulted in reduced LRC (log-rank test: +/- G-CSF, p = 0.0072).
                With accelerated radiotherapy, the efficiency of simultaneously given chemotherapy may be not as high as expected when compared to standard fractionated RT. Oropharyngeal carcinomas showed better LRC after HF-ACC-RCT vs. HF-ACC-RT; hypopharyngeal carcinomas did not. Prophylactic G-CSF resulted in an unexpected reduced local control and should be given in radiotherapy regimen only with strong hematologic indication. In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities.
                All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix. Patients underwent standard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB, III, or IVA. Negative cytologic washings and para-aortic lymph nodes were required for entry. Patients were randomized to receive either standard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU.
                Of 388 randomized patients, 368 were eligible; 177 were randomized to CF and 191 to HU. Adverse effects were predominantly hematologic or gastrointestinal in both regimens. Severe or life-threatening leukopenia was more common in the HU group (24%) than in the CF group (4%). The difference in progression-free survival (PFS) was statistically significant in favor of the CF group (P = .033). The sites of progression in the two treatment groups were not substantially different. Survival was significantly better for the patients randomized to CF (P = .018).
                This study demonstrates that for patients with locally advanced carcinoma of the cervix, the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU, and with manageable toxicity. To determine the effect of inhaled corticosteroids on lung function in patients with cystic fibrosis.
                We report a pilot study of 49 patients with cystic fibrosis and moderate to severe bronchial obstruction (forced expiratory volume in 1 second < or = 55% of the predicted value); 25 patients were given inhaled corticosteroids for 30 days (1500 micrograms of beclomethasone via spacer), and 24 patients had the same standard treatment but no inhaled corticosteroids.
                Forced vital capacity, forced expiratory volume in 1 second, and airway resistance showed significant improvement in both study groups, but thoracic gas volume and the diffusion capacity of the lung for carbon monoxide improved significantly only in the group given inhaled corticosteroids. When concomitant medications were taken into account, analysis of variance confirmed a significant effect of inhaled corticosteroids on the improvement of thoracic gas volume.
                Inhaled corticosteroids in combination with standard treatment can contribute to the improvement of lung function in patients with cystic fibrosis and moderate to severe bronchial obstruction. Our preliminary data seem encouraging enough to warrant a multicenter, long-term, blind control study.
Based on the findings of three small RCTs of moderate to severely poisoned patients, glucocorticoid with cyclophosphamide in addition to standard care may be a beneficial treatment for patients with paraquat-induced lung fibrosis. To enable further study of the effects of glucocorticoid with cyclophosphamide for patients with moderate to severe paraquat poisoning, hospitals may provide this treatment as part of an RCT with allocation concealment.