Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among 137 patients with small cell carcinoma of the lung (SCCL) treated on two consecutive protocols, leptomeningeal metastases were documented in 12 patients (9%), 10 antemortem by cerebrospinal fluid (CSF) cytology, one by myelogram, and one only at necropsy. Signs and symptoms included confusion in seven, limb weakness in six, paresthesias in three, headache in two, urinary incontinence in two, and nausea and vomiting, diplopia and neck pain in one patient each. Nine of the 12 patients had evidence of other metastases while three patients relapsed first in the CSF and one had disease only in the leptomeninges. Treatment for this complication including irradiation, intrathecal chemotherapy, or systemic chemotherapy was generally ineffective with a median duration of survival of 50 days (range 5 to 130) after diagnosis of leptomeningeal. Necropsies showed thick tumor deposits along cord, distal nerve roots, cauda equina, and in Virchow--Robbins spaces with deep invasion into adjacent neural substance in six of the seven. Leptomeningeal involvement appears to have become manifest as median survival has increased. CSF cytology should therefore be examined in patients who develop unusual neurological findings during the course of this disease and methods of prevention may need to be considered in future studies.
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PMID:Leptomeningeal carcinomatosis in small cell carcinoma of the lung. 625 38

A 58-year-old man with primary large cell carcinoma of the lung presented with rapidly progressive, bilateral visual loss. The patient was alert and oriented, had no complaints of headache, and was found to have full ocular motility. The optic disks and fundi appeared normal. No visual pathway lesions or other CNS abnormalities were detected on neuro-imaging. The authors discuss their differential diagnosis, clinical diagnostic approach, and subsequent management of this unusual patient.
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PMID:Lung cancer with visual loss. 872 43

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

Clinical trials, particularly large cooperative group trials, establish the standards that we use to treat many of our cancer patients. The process by which multi-institutional clinical trials are developed, performed and peer-reviewed in the United States is equaled by few other countries around the world. Our clinical cooperative groups should be considered an important national resource. However, they stand at an embattled crossroads. Traditionally, only two to three percent of cancer patients have been entered onto clinical trials. In the past few years, national accrual has declined even further-from approximately 22,000 to 16,000 patients annually. The reasons for this decline are unclear. Although it could simply reflect a hiatus in the activity of some groups (such as the recent reorganization of the National Surgical Adjuvant Breast and Bowel Project [NSABP]), it more likely reflects changes in our health care environment. Few managed care insurance plans permit patient entry into clinical studies on the premise that trials increase patient care costs. Yet, individualized patient care not delivered according to strict peer-reviewed standards may cost more. While this remains undetermined, oncologists in both academic and private practice are being pressured to work harder for fewer rewards. They are being told that investigational treatments are not allowed even if trials evaluating these treatments may ultimately lead to better and more cost-effective patient care. This is a sad state of affairs at a time when, on one hand, treatment for many solid tumors remains desperately inadequate and, on the other hand, new insights into tumor biology promise to alter fundamentally our approach to cancer care. Where do surgeons fit into this picture? The cooperative groups were initiated in the mid-1950s, primarily to evaluate the potential role of chemotherapy in cancer treatment. During the past forty years, surgeons have usually played a supporting role in cooperative group trials with few notable exceptions, including studies performed by the NSABP, Gynecologic Oncology Group (GOG), and Lung Cancer Study Group (LCSG). Surgeons help enroll patients on study and oversee surgical quality control but infrequently design or coordinate studies, or lead the groups administratively. It is estimated that half of all solid tumors are appropriately treated by surgical resection, but most cooperative trials still focus on the management of advanced stage disease. If we are to impact the poor survival rates of the common solid tumors, our future agenda must be to test new biologically based treatment strategies in large numbers of patients. This requires that surgeons become more educated about clinical trial methodology and increase dramatically their participation in the entire clinical trials process. A recent surgical initiative may address some of these problems. This month, the American College of Surgeons will undergo a site visit for a grant application to develop a new, surgically based clinical cooperative group. Although regarded by some as a threat to the activities of the established cooperative groups, the American College of Surgeons Oncology Group (ACoSOG) potentially provides an answer to many of the problems currently surrounding large clinical trials. The ACoSOG is a sleeping giant. The American College of Surgeons is the parent North American surgical association with a membership of over 65,000 general surgeons and surgeons in all sub-specialties. Fellowship in the American College of Surgeons is a requisite of credible surgical practice in North America and in many countries around the world. Through its publications and national and state chapter meetings, the American College of Surgeons has unparalleled ability to educate surgeons and to support new directions in surgical practice. Surgeons are the portal of entry for many solid tumor patients into their cancer care. It will be difficult for any managed care system to argue with such a large group of physicians if they are educated in clinical trials methodology and committed to improving the care of their patients through cogent, surgically based protocols. Such protocols could examine the value of a new surgical technique of technology, could assess optimal methods of tumor staging or could ask biological questions using surgical specimens. The results of these surgical trials would directly affect the design of trials for more advanced malignancies coordinated by the other cooperative groups. Surgeons who participate actively in ACoSOG protocols (and are supported by appropriate funding for doing so) will probably support trials generated by the other cooperative groups with enthusiasm. This could solve a longstanding headache, namely, the pathetically small participation by surgeons in current cooperative group activities. None of this will happen overnight. Assuming the ACoSOG initiative is funded by the NCI, the administrative and educational efforts required to establish a successful cooperative group encompassing all surgical disciplines are daunting. Many years will be necessary to bring such efforts to maturity in a smoothly functioning organization. However, the ACoSOG has the opportunity to provide a new force, energy and vision in clinical trials which could radically change our approach to patient care and could greatly strengthen the activities of the current cooperative groups.
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PMID:Surgeons: A Future Role in Clinical Trials? 1038 50

Stereotactic radiosurgery (SR) is being used with increasing frequency in the treatment of brain metastases. This study provides data from a clinical experience with radiosurgery in the treatment of cases with multiple metastases and identifies parameters that may be useful in the proper selection and therapy of these patients. From January 1993 to April 1997, 97 patients (43 women and 54 men; median age 58 years) suffering from multiple brain metastases (median 3; range 2-4) in MRI scans, received SR with the Gamma Knife. The median dose at the tumor margin was 20 Gy (range 17-30 Gy). Median tumor volume was 3900 cmm (range 100-10,000). Different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness and ataxia had been the predominant neurological symptoms. Major histologies included lung carcinoma (44%), breast cancer (21%), renal cell carcinoma (10%), colorectal cancer (8%), and melanoma (7%). The median survival time was 6 months after SR. The actual one-year survival rate was 26%. In univariate and multivariate analysis, a higher Karnofsky performance rating and absence of extracranial metastases had a significantly positive effect on survival. Local tumor control was achieved in 94% of the patients. Complications included the onset of peritumoral edema (n = 5) and necrosis (n = 1). SR induces a significant tumor remission accompanied by neurological improvement and, therefore, provides the opportunity for prolonged high quality survival. We conclude that radiosurgical treatment of multiple brain metastases leads to an equivalent rate of survival when compared to the historic experience of patients treated with whole brain radiotherapy. Patients presenting initially with a higher Karnofsky performance rating and without extracranial metastases had a median survival time of nine months. Each such case should therefore be evaluated based on these factors to determine an optimal treatment regimen.
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PMID:Prognostic factor analysis for multiple brain metastases after gamma knife radiosurgery: results in 97 patients. 1042 Oct 75

Although neutropenia increases the risk of life-threatening infections, bacterial meningitis is rarely encountered as a complication during cancer chemotherapy in adults with a solid tumor. A 66-year-old male with adenosquamous carcinoma of the lung, cT2N3M0, stage IIIB, was enrolled in a phase I trial of chemoradiotherapy and treated with cisplatin 80 mg/m2 (122 mg/ body) on day 1, vinorelbine 20 mg/m2 (32 mg/body) on days 1 and 8 and thoracic radiotherapy 30 Gy/15 fractions, beginning on day 2, with dexamethasone administered for antiemesis at a dose of 16 mg on day 1, 8 mg on days 2 and 3, 4 mg on day 4 and 2 mg on day 5. The patient developed headache and fever on day 6 of the second cycle of the treatment and bacterial meningitis was diagnosed based on the findings of consciousness disturbance, an elevated peripheral blood leukocyte count and numerous leukocytes in the cerebrospinal fluid. In spite of the doctor's delay in establishing the exact diagnosis, the bacterial meningitis in this case was successfully treated with intensive antibiotic therapy. This life-threatening complication, equivalent to a grade 4 non-hematological adverse reaction, was not counted as dose-limiting toxicity in the current phase I trial, because there are only a few reports of bacterial meningitis associated with cancer chemotherapy and it developed in this case without any associated decrease in the peripheral blood leukocyte count.
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PMID:Bacterial meningitis observed in a phase I trial of vinorelbine, cisplatin and thoracic radiotherapy for non-small cell lung cancer: report of a case and discussion on dose-limiting toxicity. 1109 38

A 55 year old female receiving gemcitabine for stage IV non-small cell carcinoma of the lung developed the clinical-radiologic syndrome of posterior reversible encephalopathy syndrome (PRES). She had clinical manifestations of headaches, increasing somnolence and tonic-clonic seizures. The fluid-attentuated inversion recovery (FLAIR) MR imaging sequence conspicuously showed bihemispheric, symmetrical cortical and subcortical white matter hyperintensities that preponderantly involved the parietal and occipital lobes. Diffusion-weighted imaging (DWI) sequence reflected the preponderant existence of vasogenic edema in the involved areas. MR spectroscopy showed no significant N-acetyl aspartate (NAA) depletion or lactate elevation prospectively, indicating the absence of significant neuronal loss and reversibility of the brain parenchymal changes. The clinical and radiologic manifestations essentially resolved completely with discontinuation of the drug.
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PMID:Gemcitabine-associated posterior reversible encephalopathy syndrome: MR imaging and MR spectroscopy findings. 1129 55

Structurally novel compounds able to block voltage-gated Ca2+ channels (VGCCs) are currently being sought for the development of new drugs directed at neurological disorders. Fluorescence techniques have recently been developed to facilitate the analysis of VGCC blockers in a multi-well format. By utilising the small cell lung carcinoma cell line, NCI-H146, we were able to detect changes in intracellular Ca2+ concentration ([Ca2+](i)) using a fluorescence microplate reader. NCI-H146 cells have characteristics resembling those of neuronal cells and express multiple VGCC subtypes, including those of the L-, N- and P-type. We found that K+-depolarisation of fluo-3 loaded NCI-H146 cells causes a rapid and transient increase in fluorescence, which was readily detected in a 96-well plate. Extracts of Australian plants, including those used traditionally as headache or pain treatments, were tested in this study to identify those affecting Ca2+ influx following membrane depolarisation of NCI-H146 cells. We found that E. bignoniiflora, A. symphyocarpa and E. vespertilio caused dose-dependent inhibition of K+-depolarised Ca2+ influx, with IC(50) values calculated to be 234, 548 and 209 microg/ml, respectively. This data suggests an effect of these extracts on the function of VGCCs in these cells. Furthermore, we found similar effects using a fluorescence laser imaging plate reader (FLIPR) that allows simultaneous measurement of real-time fluorescence in a multi-well plate. Our results indicate that the dichloromethane extract of E. bignoniiflora and the methanolic extract of E. vespertilio show considerable promise as antagonists of neuronal VGCCs. Further analysis is required to characterise the function of the bioactive constituents in these extracts and determine their selectivity on VGCC subtypes.
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PMID:Fluorescence detection of plant extracts that affect neuronal voltage-gated Ca2+ channels. 1198 93

Facial pain is a rare presenting symptom of nonmetastatic lung carcinoma. Referred pain from tumor invasion and compression of the vagus nerve was the presumed cause in the 31 cases published to date. We report 2 additional cases having an unusual clinical feature, namely, both had radiographic evidence of malignancy absent on initial chest films. Severe facial pain in both cases was explained by pulmonary carcinoma detected only through further investigations. From these cases follows the notable conclusion that referred facial pain of malignant origin can occasionally precede the appearance of neoplasm on routine chest films. It is therefore important for physicians to be familiar with the clinical features of this syndrome in order to choose appropriate further diagnostic testing in patients who may be at risk.
Headache 2003 May
PMID:Facial pain as the presenting symptom of lung carcinoma with normal chest radiograph. 1275 57

This study was designed as a multicenter, randomized, double-blind, placebo-controlled trial. Patients were randomized by center to placebo (16 patients, 31%), oral bexarotene 300 mg/m2/day (21 patients, 40%), or oral bexarotene 600 mg/m2/day (15 patients, 29%) following demonstration of stable or responsive disease after first-line chemotherapy. The study was prematurely terminated because of slow accrual after 54 patients enrolled. Median time to progression (TTP) from the beginning of study drug treatment was 56 days for placebo, 82 days for moderate-dose bexarotene (300 mg/m2/day), and 128 days for high-dose bexarotene (600 mg/m2/day) (P = 0.56, log-rank test). For prior chemotherapy responders only, median TTP from the beginning of study drug treatment was 56 days for placebo, 146 days for moderate-dose bexarotene, and 177 days for high-dose bexarotene. Of note, there were more chemotherapy responders randomized to the placebo group (63%) than the bexarotene treatment arms (48% and 47%), further supporting a bexarotene-related improvement in TTP. Bexarotene-related toxicity was manageable and consisted primarily of elevated serum triglycerides and asthenia, skin toxicity (dryness, peeling, flaking), thyroid dysfunction, and headache. Because this study was closed prematurely, it does not have the statistical power to detect differences among the treatment groups. This study shows that patients can tolerate bexarotene at initial doses up to 600 mg/m2/day after platinum-based chemotherapy and that bexarotene may have the potential to delay disease progression in patients with advanced non-small-cell lung cancer with previously stable or responsive disease following platinum-based chemotherapy.
Clin Lung Cancer 2001 Feb
PMID:Placebo-controlled trial of bexarotene, a retinoid x receptor agonist, as maintenance therapy for patients treated with chemotherapy for advanced non-small-cell lung cancer. 1470 Apr 80


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