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

This phase I study investigated flavone acetic acid (FAA) given as a 12-h intravenous infusion every 3 weeks in the absence of urinary alkalinisation. Cohorts of three patients were treated at doses of 7, 10 and 13 g/m2. One subject had colon cancer; 5, renal cancer; and 3, lung cancer. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in four patients, 1 in two subjects and 2 in three cases. The maximum tolerated dose was 13 g/m2. The dose-limiting toxicities were WHO grade 3 hypotension and grade 3 diarrhoea. Other toxicities included lethargy and dizziness, nausea, temperature fluctuation, myalgia and dry mouth, but no significant myelosuppression was encountered. One patient receiving 10 g/m2 for renal cancer showed a partial response that lasted for 3 months and included the resolution of pulmonary and cutaneous metastases. The pharmacokinetics showed large interpatient variability. At 12-16 h post-infusion, the plasma elimination profile entered a plateau phase, with frequent increases in concentration suggesting enterohepatic recycling. Neither peak FAA levels nor AUC values were dose-dependent at the doses studied. Peak plasma levels were 101-402 micrograms/ml and AUC (0-48 h) values were 75-470 mg ml-1 min. Plasma protein binding varied with total concentration. Two metabolites were detected in the plasma, and both also underwent apparent enterohepatic recycling. Repeat dosing resulted in decreases of up to 48% in peak levels and AUC values for FAA in three of six patients. Of the total FAA dose, 39%-77% was excreted in the urine as FAA or metabolites within 2 days. The dose recommended for further phase II studies is 10 g/m2.
 ...
PMID:A phase I and pharmacokinetic study of 12-h infusion of flavone acetic acid. 155 Nov 73

A phase I clinical study of intravenous Tegafur was conducted in nineteen previously treated patients with primary lung cancer. The dose of Tegafur was elevated from 1.0 to 3.0 g/m2/day for five consecutive days to determine the maximum tolerated dose. The dose-limiting factors were gastrointestinal and neurological toxicity and fatigability observed with the dose level of 2.5 g/m2/day for 5 days. Hematologic, hepatic and renal toxicities were not observed. Gastrointestinal toxicity including nausea, vomiting, anorexia and diarrhea of over grade 2 were seen to result from the dose of 2.5 g/m2/day. Neurological toxicity consisted of headache, dizziness, anxiety and depression. At the dose level of 2.0 g/m2/day, one patient, who had epileptic seizures in the past, experienced a psychomotor seizure. Depression (Grade 2 CNS toxicity) was observed at the dose level of 3.0 g/m2/day. Dose limiting factors were neurological toxicities. The pharmacokinetics of tegafur and 5-FU (the active form of Tegafur) has been studied in all patients. Serum level of tegafur was measured by HPLC method, and serum level of 5-FU was analyzed by GC-MS method. At the dose level greater than 2.0 g/m2/day for 5 days, the mean serum 5-FU values appear over the therapeutic range (0.1 micrograms/ml). In conclusion, 2.5 g/m2/day for 5 days was considered to be MTD, and 2.0 g/m2/day for 5 days intravenous administration was recommended for the phase II trial of single agent chemotherapy.
 ...
PMID:[High-dose Tegafur (FT) for primary lung cancer: a phase I trial]. 201 1

Amonafide (benzisoquinolinedione, NSC 308847) is a new synthetic imide antineoplastic agent with DNA intercalative properties that has been evaluated in a phase I clinical trial. The drug was administered as a single intravenous (IV) infusion over 30 to 120 minutes repeated every 28 days. Ninety-five courses of therapy at doses ranging from 18 to 1,104 mg/m2 were administered to 38 patients with refractory solid tumors. Granulocytopenia was dose limiting. Leukopenia was seen in 13 of 31 courses at doses of 690 mg/m2 or greater. Life-threatening granulocytopenia (less than or equal to 250 microliters) was noted in 1/6 patients treated at 800 mg/m2, 1/8 patients treated at 918 mg/m2, and 2/5 patients treated at 1,104 mg/m2. No definite relationship between myelotoxicity and prior treatment status was noted. Rate-of-infusion dependent, nonhematologic toxicities included diaphoresis, flushing, dizziness, and tinnitus, all of which were ameliorated by increasing the duration of drug infusion to 120 minutes. In addition, nausea and vomiting (grades 1 and 2) were seen in 29/56 courses at doses greater than or equal to 519 mg/m2, but were easily controlled by phenothiazine antiemetics. Amonafide plasma and urine concentrations were determined by high-pressure liquid chromatography (HPLC). Plasma concentrations declined biexponetially with a terminal harmonic mean terminal half-life (t 1/2) of 5.5 h. The mean apparent volume of distribution at steady-state and total body clearance were 532 L/m2 and 84 L/h/m2, respectively. Less than 5% of the total dose of amonafide was excreted unchanged in the urine. Antitumor activity has been noted in one patient with non-small-cell lung cancer (one complete response exceeding 29 months duration) and in one patient with prostatic cancer (complete pain relief and improvement in bone scan for 9 months). The recommended dose for phase II trials with this schedule of amonafide is 918 mg/m2 with dose escalation to amonafide is 918 mg/m2 with dose escalation to myelotoxicity.
 ...
PMID:Phase I clinical investigation of amonafide. 254 5

Nabilone, a synthetic cannabinoid, and Prochlorperazine were compared in a double-blind crossover study of 34 patients with lung cancer undergoing a 3-day schedule of chemotherapy with Cyclophosphamide, Adriamycin and Etoposide. Symptom scores were significantly better for patients on nabilone for nausea, retching and vomiting (P less than 0.05). Fewer subjects vomited with nabilone (P = 0.05) and the number of vomiting episodes was lower (P less than 0.05); no patients on nabilone required additional parenteral anti-emetic. More patients preferred nabilone for anti-emetic control (P less than 0.005). Adverse effects common with nabilone were drowsiness (57%), postural dizziness (35%) and lightheadedness (18%). Euphoria was seen in 14% and a "high" in 7%. Erect systolic blood pressure was lower in nabilone patients on Day 1 (P = 0.05) but postural hypotension was a major problem in only 7%. Nabilone is an effective oral anti-emetic drug for moderately toxic chemotherapy, but the range and unpredictability of its side-effects warrant caution in its use.
 ...
PMID:Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy. 631 40

A 62-year-old man was given a diagnosis of small cell lung cancer, and received 6 courses of combination chemotherapy (PE therapy) composed of cisplatin (80 mg/m2, day 1) and etoposide (100 mg/m2, days 1, 2, 3). Multiple brain metastases were found, and whole brain irradiation (44 Gy) was given. Eleven months after radiotherapy, he suffered from dizziness and abnormal gait. Enhanced CT of the head showed slight enlargement of the lateral ventricles and markedly low density of the white matter, but no evidence of intracranial tumor involvement. A magnetic resonance scan (axial T2-weighted) showed symmetric extensive hyperintensity in the white matter. Treatment-related leukoencephalopathy caused by the PE therapy and whole brain irradiation was diagnosed. He was alive 8 months after the appearance of neurological symptoms, without recurrence of lung cancer. A search of the literature revealed no previous report of leukoencephalopathy related to PE therapy.
 ...
PMID:[Leukoencephalopathy in a patient being treated for small cell lung cancer]. 854 87

We tested paclitaxel (Taxol) and low dose hydroxyurea as second line therapy in 30 patients with non-small cell lung cancer since both drugs are active against non-small cell lung cancer in other settings, and since hydroxyurea may reverse chemotherapy resistance by disrupting double minute chromosomes. Hydroxyurea 500 mg was given orally each Monday, Wednesday, Friday starting 1 week before paclitaxel, and continuing until removal from study. Paclitaxel 135 mg/m2 was given i.v. over > or = 1 h every 3 weeks with dexamethasone, diphenhydramine, and ranitidine. Patients could have paclitaxel doses escalated to 175 mg/m2 in course 2 and to 200 mg/m2 in course 3, where tolerated. Sixteen males and 14 females were treated. All patients had previously received a single cisplatin-based chemotherapy regimen and 23 had previously received radiotherapy. Twelve patients had adenocarcinomas, six had squamous cell carcinomas, and 12 had large cell carcinomas. Eight patients had Stage IIIb cancers and 22 had Stage IV. Paclitaxel doses were 135 mg/m2 in 56 courses, 175 mg/m2 in 24, and 200 mg/m2 in 15. Treatment was well tolerated. Median granulocyte nadirs were 2.5 (x 10(9)/l) for paclitaxel 135 mg/m2, 1.8 for 175 mg/m2, and 1.3 for 200 mg/m2. No patient developed febrile neutropenia, and none required a dose reduction. Two patients had reversible anaphylaxis. Other toxicities were quite tolerable. They included fatigue, myalgias, dizziness, paresthesias, diarrhea, alopecia, mucositis, flushing, headache, swollen red hands, and anxiety. One patient had a partial remission and 15 had stable disease (including six with minor responses). Median survival was 20 (95% CI, 12-34) weeks, with 19% of patients remaining alive at 1 year from initiation of treatment. This is a well-tolerated regimen with modest activity as second line chemotherapy for patients with non-small cell lung cancer previously treated with cisplatin regimens. Higher doses would be feasible and other strategies are now being explored.
Lung Cancer 1996 Aug
PMID:Paclitaxel plus hydroxyurea as second line therapy for non-small cell lung cancer. 886 29

Paraneoplastic neurologic syndromes are disorders of the nervous system function caused by cancer but not due to metastatic disease, vascular or metabolic deficits, infections, nutritive deficiency, nor side effects of antineoplastic drugs or irradiation. Immunologic factors probably play the crucial role in the pathogenesis of paraneoplastic neurologic syndromes, but nonimmunologic mechanisms that include metabolic abnormalities and competition for substrate are also involved. Paraneoplastic cerebellar degeneration most commonly occurs in the setting of gynecologic cancers, but it accompanies the small-cell lung cancer too. Other tumors are infrequently associated with cerebellar degeneration. Several paraneoplastic antibodies have been identified in patients with paraneoplastic cerebellar degeneration. Their association with particular cancers may help identify an occult lesion. Anti-Yo antibodies are directed against Purkinje cell antigens and occur in patients with cerebellar degeneration who have breast cancer or gynecologic tumors. A target antigen of anti-Yo antibody is CDR2 protein that is normally expressed only in the brain and testis. Patients with paraneoplastic cerebellar degeneration present with dizziness, nausea and vomiting followed by gait instability, diplopia, gait and appendicular ataxia, dysarthria and dysphagia. Therapeutic options include tumor excision, chemotherapy and/or irradiation, and adjuvant therapy with glucocorticoids, immunoglobulins and plasmapheresis. The role of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration is still uncertain. Reports of its efficacy are anecdotal. We present patient with paraneoplastic cerebellar degeneration with positive anti-Yo antibodies and tumor of the ovaries whose neurologic status significantly improved after four daily plasmaphereses, which was accompanied by a fourfold decrease in the anti-Yo antibodies titer. Further investigations are needed to define a protocol for plasmapheresis in the treatment of patients with paraneoplastic syndromes.
 ...
PMID:[Importance of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration]. 1512 96

A 68-year-old man suffered right facial palsy and left deafness, however, his condition was considered to be idiopathic and he was followed. Three months later, bloody sputum and hoarseness caused him to be admitted to our hospital. An abnormal shadow was detected in the right upper lung field and adenocarcinoma of the lung with multiple brain metastases was diagnosed. He underwent gamma-knife radiosurgery for the brain lesions and subsequent systemic chemotherapy consisting of combined carboplatin and paclitaxel, which were not effective. Subsequently various neurological symptoms appeared, such as muscle weakness of the extremities, dizziness, and gait disturbance. Adenocarcinoma cells confirmed in the cerebrospinal fluid were similar to those in the obtained by transbronchial curetting. Whole-brain irradiation was performed, however, the neurological symptoms worsened and he died. Leptomeningeal carcinomatosis is difficult to diagnose while the patient is alive. It is thought that cranial neuropathy due to leptomeningeal carcinomatosis is a rare form of onset for lung cancer.
 ...
PMID:[A case of lung cancer with cranial neuropathy as the first sign of onset due to metastatic leptomeningeal carcinomatosis]. 1636 64

A case of an 82-year-old woman who experienced repeated falls is described. She exhibited a cardioinhibitory carotid sinus hypersensitivity after right carotid sinus massage (CSM), but without evidence of orthostatic hypotension. After a pacemaker was implanted, she did not experience any falls, dizziness or syncope. Her balance eventually deteriorated, but she remained cognitively intact and died from lung cancer at the age of 89 years. Neuropathological examination showed only age-related Alzheimer's disease pathology and a few alpha-synuclein-positive granular deposits and neurites in the dorsal nucleus of the vagus and solitary tract nucleus in the medulla, but a marked alpha-synuclein pathology in the stellate ganglia. The cardioinhibitory element of her CSM was possibly because of the alpha-synuclein pathology in the ganglion, which impaired sympathetic transmission. This case shows another phenotype among patients with alpha-synucleinopathy.
 ...
PMID:Carotid sinus hypersensitivity associated with focal alpha-synucleinopathy of the autonomic nervous system. 1691 54

Brain metastases are frequent features during the course of patients with lung carcinoma. The aim of this study was to investigate prognostic factors for patients with brain metastasis from lung cancer. Eighty-eight patients with brain metastasis from lung cancer were enrolled in the study. Eighty-two of cases were male, six were female and the mean age was 57.5 +/- 10.4 years. The most common symptoms were headache (32.9%) and dizziness (32.9%). Fifty-two (59.1%) patients had solitary brain metastasis and the most frequent metastasing site was parietal lobe (34.1%). The median survival times were 3 months after diagnosis of lung carcinoma and 1.5 months after diagnosis of brain metastasis. Although the absence of brain metastasis at the moment of diagnosis, metachronous metastasis, central localization of the tumour, chemotherapy administration and surgical treatment of brain metastasis are good prognostic factors affecting survival after the diagnosis of lung carcinoma, the positive factors affecting survival after brain metastasis are central localization of tumour, chemotherapy administration and surgical treatment of brain metastasis. In conclusion, performing the combination of cranial radiotherapy, chemotherapy, surgical therapy and supporting therapy should be evaluated in all appropriate patients with brain metastasis from lung cancer.
 ...
PMID:[Factors affecting the prognosis in patients with primary lung cancer and brain metastases]. 1700 40


1 2 3 Next >>