Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We undertook a phase I trial using fixed-dose cisplatin, escalating doses of etoposide, and reinfusion of previously obtained autologous bone marrow in 29 relapsed or refractory small cell and non-small-cell lung cancer patients. Median age was 59 years (range of 38-68 years). Three patients had small-cell and 26 patients had non-small-cell lung cancer. Patients received i.v. cisplatin 200 mg/m2 over 5 days and i.v. etoposide 600 mg/m2/day for 3 days (total of 1,800 mg/m2) that was escalated to 800, 1,000, 1,200, 1,400, and 1,600 mg/m2/day for 3 days (total of 2,400-4,800 mg/m2). Cryopreserved autologous bone marrow was thawed and reinfused through a central venous catheter the second day after the completion of chemotherapy. Toxicities included nausea, vomiting, alopecia, high-tone hearing loss, mucositis, diarrhea, renal insufficiency, metabolic acidosis, and severe myelosuppression. The duration of neutropenia (less than 500 neutrophils/microliter) ranged from 5 to 22 days (median of 11 days) and the duration of severe thrombocytopenia (platelets of less than 20,000/microliters untransfused) ranged from 2 to 19 days (median of 9 days). Reversible renal insufficiency (peak serum creatinines of 6.7, 6.6, 4.3, and 3.5 mg/dl) occurred in four patients who completed the therapy. In three patients, death occurred within 4 weeks of chemotherapy and marrow reinfusion. Three complete and 12 partial remissions (range of 1+(-)22+ months, median of 3 months) were observed. No response was noted in eight patients and tumor progression within 1 month of transplant occurred in two patients. The maximally tolerated dose of etoposide was 1,400 mg/m2/day (total of 4,200 mg/m2), since two of three patients developed life-threatening diarrhea at the 1,600 mg/m2/day (total of 4,800 mg/m2) dose. The encouraging antitumor effects of this regimen suggest that this approach may be useful therapy for lung cancer and other tumors sensitive to VP-16 and cisplatin.
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PMID:Phase I trial of high-dose etoposide, high-dose cisplatin, and reinfusion of autologous bone marrow for lung cancer. 215 15

Clinical evaluation, safety and kinetics in serum of sulbactam/cefoperazone (SBT/CPZ) in patients with lower respiratory tract infections have been studied in a multicenter trial participated by 28 institutions in Kyushu area during a period of 13 months from March 1987 to March 1988. 1. Mean peak serum levels of SBT and CPZ in 35 patients up to 4 hours after intravenous infusion of 2 g of SBT/CPZ were 38.2 +/- 17.3 micrograms/ml for SBT and 104.3 +/- 31.4 micrograms/ml for CPZ. Serum half-lives of SBT and CPZ were 0.76 hour and 1.53 hours, respectively. These results were in similar ranges to those reported elsewhere for SBT/CPZ. 2. Serum half-lives of SBT and CPZ after intravenous infusion of 2 g of SBT/CPZ were not significantly prolonged in patients with moderate liver or kidney dysfunctions. 3. Clinical efficacy rates of SBT/CPZ in 217 patients were 93.1% (81/87) for pneumonia, 93.3% (14/15) for lung abscess, 78.9% (15/19) for acute exacerbation of chronic bronchitis, 57.1% (4/7) for diffuse panbronchiolitis, 72.4% (21/29), 74.4% (32/43) and 100% (9/9) for infections concurrent to bronchiectasis, chronic respiratory disease and pulmonary emphysema, respectively. Those were 50% (1/2) for bronchitis associated with lung cancer and 66.7% (4/6) for empyema. The overall efficacy rate was 83.4% (181/217). 4. Clinical efficacy rate of SBT/CPZ for pneumonia in patients with underlying diseases such as lung cancer, pulmonary tuberculosis and pneumoconiosis, etc, was 85.3% (29/34) and was not significantly different from the efficacy rate of 98.1% (52/53) in patients without these underlying diseases. 5. Of 30 patients who failed to respond of previous antibiotic treatments, 21 were effectively treated by SBT/CPZ. 6. Bacteriological eradication rates against Pseudomonas aeruginosa, Haemophilus influenzae and Streptococcus pneumoniae were 42.9% (9/21), 87.5% (14/16) and 100% (5/5), respectively. The overall eradication rate in all cases including polymicrobial infections was 72.8% (67/92). 7. The high levels of peak serum concentration of CPZ, and the difference between serum levels of SBT and of CPZ seemed to contribute to the high clinical efficacy. 8. Adverse reactions occurred in 2.8% (6/217) of the patients, and consisted primarily of rash and diarrhea. Laboratory abnormalities were observed in 8 patients during the study. These were elevations of S-GOT and S-GPT, and eosinophilia. 9. SBT/CPZ is a very useful drug in the treatment of lower respiratory tract infections as it has become available just in time when increase in resistant organisms to beta-lactams is notable.
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PMID:[Clinical evaluation of sulbactam/cefoperazone in lower respiratory tract infections]. 219 54

Twenty-eight patients with metastatic and/or recurrent non-small-cell lung cancer were treated with a new sequential combination of escalating doses of cisplatin (50, 75, and 100 mg/m2 IV X 1) followed by 5-FU infusion (40 mg/m2/hour X 72) and etoposide (80 mg/m2/day X 3). Three patients received concurrent external radiation therapy. Eleven of the 28 (39%) had a partial response to chemotherapy. Four others had a minor response. One partial responder became a complete responder by surgical excision of residual cancer. Median time to response was 6 weeks followed by a median response duration of 4 months. In responders, chemotherapy was discontinued at the time of maximal response. Median survival was 7 months. Chemotherapy was well tolerated with absence of leucopenia, thrombocytopenia, and nausea and vomiting in a majority of courses. The common toxicities were alopecia (100%), leucopenia (35%), nausea and vomiting (30%), and electrolyte imbalances (27%). Reversible nephrotoxicity, thrombocytopenia, anemia, mucositis, and diarrhea were infrequent. The response rate in stage IV was less than in stage III. The combination of moderate doses of cisplatin, 5-FU infusion, and etoposide provides a new palliative chemotherapy that is well tolerated with concurrent/sequential radiation therapy and may be useful in the multimodality treatment of non-small-cell lung cancer.
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PMID:Toxicity of FED chemotherapy in non-small-cell lung cancer. 244 89

Fifteen patients with Stage IV lung cancer both untreated and previously treated were enrolled into a high-dose chemotherapy program with multiple alkylating agents and autologous bone marrow reinfusion. Eight patients received cyclophosphamide at 7.5 gm/m2 over 3 days with thiotepa escalated from levels of 1.8 mg/kg to 6.0 mg/kg over 3 days. Seven patients received the above dose of cyclophosphamide plus thiotepa at 675 mg/m2 and oral melphalan escalated from levels of 0.75 mg/kg to 2.5 mg/kg over 3 days. Both regimens are part of larger Phase I-II clinical studies. The median time to recovery of more than 500 granulocytes and more than 50,000 platelets per microliter was 16 and 27 days, respectively. Two patients died as a consequence of severe, overwhelming infections during their period of aplasia. Of the 13 evaluable patients, no patients achieved a complete response and seven patients (47%) obtained a partial response. The median duration of response was 12 weeks. Other nonhematologic toxicities included nausea/vomiting, diarrhea, mucositis, skin rash, hemorrhagic cystitis, and cardiomyopathy. Since there are substantial toxicities associated with high-dose chemotherapy and responses of such brief duration, further investigation with these drug combinations is not warranted.
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PMID:High-dose, multiple-alkylator chemotherapy with autologous bone marrow reinfusion in patients with advanced non-small cell lung cancer. 253 52

Trimetrexate is a nonclassical antifolate with greater preclinical antitumor activity than methotrexate. Fourteen patients with stage III or IV non-small-cell lung cancer who had not previously received chemotherapy were given trimetrexate (12 mg/m2 intravenously daily for 5 days) every 3 weeks. No major objective responses were observed (95% confidence limits: 0-20%). Ten of the 14 patients had grade 2 or greater toxicity, with 50% experiencing grade 2 or greater leukopenia and/or thrombocytopenia. Nausea, vomiting, rash, mucositis, diarrhea, and serum glutamic-oxaloacetic transaminase (SGOT) elevations were also seen. At the dosage and schedule of trimetrexate used, no responses occurred in this population of patients with non-small-cell lung cancer. With the low response rate and the observed degree of myelosuppression, trimetrexate appears to have limited utility in this disease.
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PMID:Phase II trial of trimetrexate in patients with stage III and IV non-small-cell lung cancer. 253 13

Sixty previously untreated patients with newly diagnosed advanced-stage lung cancer (21 small-cell, 39 non-small-cell) received chemotherapy with cisplatin and etoposide. Bleomycin was also used in the patients with non-small-cell lung cancer. During the first cycle of chemotherapy, 30 patients received antiemetic therapy with intermittent metoclopramide (regimen A), and the other 30 patients received continuous infusion metoclopramide (regimen B). During the second course of chemotherapy, patients were switched to the alternate regimen. Regimen A consisted of lorazepam, 1 mg, orally; dexamethasone, 10 mg, intravenously (IV) every four hours for three doses; diphenhydramine, 0.5 mg/kg, IV every four hours for three doses; metoclopramide, 1 mg/kg, IV bolus every two hours for six doses. Regimen B was identical to A except metoclopramide was administered as 1 mg/kg, IV bolus followed by 0.5 mg/kg/h for ten hours. Fifty-eight patients completed both antiemetic regimens. Thirty-nine of the 58 patients had total control of acute nausea and vomiting (0-1 episodes) with regimen A or B. Fourteen patients had poor control of acute nausea and vomiting (more than one episode) with regimen A but total control with regimen B. Five patients had poor control with either regimen. Dystonic reactions, akathisia, or diarrhea occurred in 20 of the 58 patients on regimen A, but in only eight of the 58 patients on regimen B. Compared with intermittent bolus, continuous infusion metoclopramide is more effective in total control of acute nausea and vomiting and has less toxicity.
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PMID:Comparison of intermittent versus continuous infusion metoclopramide in control of acute nausea induced by cisplatin chemotherapy. 254 88

Eleven aged patients over 65 years of age with advanced lung cancer (mean age = 70.8 +/- 1.4, non-small cell:small cell = 9:2, stage III:IV = 5:6) were treated with combination chemotherapy consisting of cisplatin (50 or 80 mg/m2) and vincaloids (vindesine 3 mg/m2 or etoposide 80 mg/m2). To evaluate this cisplatin combination therapy, the aged group was compared with a young group consisting of eleven patients (mean age = 53.3 +/- 1.7, non-small cell:small cell = 9:2, stage III:IV = 5:6) matched for cell type, stage and dose regimen. The mean dose of cisplatin was 58.2 mg/m2 in the aged and 63.6 mg/m2 in the younger group. A notable reduction in tumor size was observed in 9.1% of the aged and 27.3% of the young, while one-year survival rate was 63.6% in the aged and 72.7% in the young. The common side effects were nausea and vomiting, while diarrhea was seen in 18.2% of the aged. Neutropenia, anemia and thrombocytopenia were found in both groups and the time course of myelosuppression in the aged (18.2 +/- 0.8 days) was significantly shorter than that in the younger patients (22.0 +/- 1.4 days, p less than 0.05). With regard to nephrotoxicity, creatinine clearance rate in the aged decreased remarkably from 56.9 to 38.9 ml/min, while there was no significant change in BUN, serum creatinine and urine NAG between the aged and the young. Disorders of electrolytes such as hypokalemia and hyponatremia were seen in 45.5% of the aged. We conclude that advanced lung cancer in the aged was effectively treated with cisplatin combination therapy with tolerable nephrotoxicity and myelosuppression.
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PMID:[Cisplatin combination chemotherapy in advanced lung cancer in the aged]. 260 73

The mean annual rate of decline of the probability of dying 5 years of age in developing countries is 2.5%. Nevertheless disease accounts for a considerable proportion of premature deaths. The leading causes of death in these countries, in order, include respiratory disease, diseases of the circulatory system, low birth weight, diarrhea, measles, injuries, malnutrition, and neoplasms. These conditions represent diseases of poverty and affluence. Respiratory infections are common among 5-year old children and cause a high proportion of child deaths. Circulatory diseases tend to be limited to adults. Control of hypertension, diet, smoking prevention, and exercise can prevent circulatory diseases. The risk of dying in infancy and childhood and of developmental disabilities is higher among low birth weight infants than those who weigh 2500 gm. In Bangladesh, 50% of infants weight 2500 gm. Low birth weight is the underlying cause of death for many infants who die of respiratory infections and diarrhea. Oral rehydration can successfully treat most diarrhea cases. Malnutrition and diarrhea tend to occur together and feed off each other. In fact malnourished people are more susceptible to all infections. Malnourished children suffer from disabilities in development and growth. The greatest sufferers of measles are infants and malnourished children. Immunization of all =or 9-month old infants would eradicate measles. Children and young adults are at the highest risk of injuries. Lung cancer is on the rise in developing countries due to the increase of tobacco smoking. Various means of controlling malaria are use of mosquito nets, antimalarial drugs, reduction of mosquito breeding places, and pesticides. The new infectious disease, AIDS, has emerged as a considerable health problem in developing countries. High priority research areas are vaccines for Streptococcus pneumonia, Plasmodium app., rotavirus, Salmonella typhi (Ty21a), and Shigella spp.
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PMID:Disease problems in the Third World. 269 79

Sixteen patients with lung cancer or mesothelioma have been treated with escalating doses of carboplatin. Five patients (10 courses) were given 800 mg/m2, four patients (five courses) 1200 mg/m2 and seven patients (eight courses) 1600 mg/m2. Myelosuppression was the major toxicity encountered. The median duration of grade 4 neutropenia ranged from 1 day (800 mg/m2) to 11 days (1600 mg/m2) and the median duration of grade 4 thrombocytopenia ranged from 1 day (800 mg/m2) to 7 days (1600 mg/m2). The median fall in haemoglobin (Hb) ranged from 2.2 g/l (800 mg/m2) to 3.6 g/l (1600 mg/m2). Nephrotoxicity was encountered at all dosages and was in part, though not entirely, dose related. 2/9 patients receiving 800 mg/m2 and 4/6 of the patients receiving 1600 mg/m2 had a fall in glomerular filtration rate (GFR) greater than 25% but less than 50%. 800 mg/m2 of carboplatin was well tolerated, the performance status in 9/10 (90%) courses being 0-1 (ECOG scale). At 1600 mg/m2 in 6/8 (75%) courses the performance status was 2-4. There was one treatment-related death from neutropenia at this dose level. The severity of nausea and vomiting was not dose related but other toxicities including diarrhoea, alopecia, mild neuropathy and ototoxicity and possible CNS toxicity occurred at doses of 1200 mg/m2 and over. 5/7 patients with small cell lung cancer achieved a complete or partial response to treatment.
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PMID:High dose carboplatin in the treatment of lung cancer and mesothelioma: a phase I dose escalation study. 282 9

A total of 144 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin/etoposide (PE) or ifosfamide/etoposide (IE) combination chemotherapy. PE consisted of cisplatin, 80 mg/m2, intravenously (IV) on day 1, and etoposide, 150 mg/m2, IV on days 3 through 5. IE consisted of ifosfamide, 1,500 mg/m2, IV on days 1 through 5, and etoposide, 120 mg/m2, IV on days 3 through 5. Six cycles were administered in 3-week intervals. Nonresponders were switched immediately to CAV, consisting of cyclophosphamide, 600 mg/m2, IV on days 1 and 2, Adriamycin (Adria Laboratories, Columbus, OH), 50 mg/m2, IV on day 1, and vincristine, 2 mg, IV on day 1. Patients obtaining complete remission (CR) received prophylactic cranial irradiation with 30 Gy. After completion of chemotherapy, patients with limited disease received chest irradiation with 45 Gy. No maintenance therapy was given to patients in CR. Minimum follow-up was 2 years. Of the 141 patients evaluable, the overall response rate was 65% in PE therapy and 68% in IE therapy. The CR rate was 32% v 20% for all patients, 50% v 24% for limited disease, and 22% v 18% for extensive disease, all in favor of PE therapy. Median survival for all patients was 11.6 months v 9.4 months, for limited disease 14.8 months v 11.0 months, and for extensive disease 8.9 months v 7.5 months, all preferring PE therapy. The 2-year survival rate was higher in PE therapy than in IE therapy for all patients (12% v 9%) and for limited disease (23% v 10%), but not for extensive disease (5% v 9%). Median progression-free survival was 7.5 months v 6.0 months for all patients, 12.2 months v 8.8 months for limited disease, and 5.9 months v 4.4 months for extensive disease, all in favor of PE. Relapse in the area of the primary tumor was found less often after PE than after IE therapy (25% v 38%). Response to second-line CAV was seen in 30% of patients with prior PE and 43% with prior IE therapy, but was usually short lasting, and only one patient achieved CR. Toxicity included three lethal complications. Nausea, vomiting, diarrhea, and skin lesions occurred more often after PE than after IE therapy. These results suggest that PE is superior to IE chemotherapy in limited-stage, but not in extensive-stage SCLC, and that CAV is cross-resistant to PE, as well as to IE in the majority of patients.
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PMID:Cisplatin/etoposide versus ifosfamide/etoposide combination chemotherapy in small-cell lung cancer: a multicenter German randomized trial. 282 10


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