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)

In this pharmacokinetics study, concentrations of toremifene (TOR), a new antiestrogen, were measured after a 7-day oral treatment in serum, lung, and tumor tissue to determine the optimal dose of TOR for the modulation of clinical multidrug resistance in patients with lung cancer. Target levels of the antiestrogen were based on previous in vitro studies. Altogether, 18 patients with operable lung tumors were studied. TOR was given in an open, nonrandomized, phase I study at three different dose levels. The medication consisted of oral TOR given for 7 days at either 240, 480, or 600 mg/day before surgical removal of the tumor. At least five patients were scheduled to be included at each dose level, with all five receiving the full course of therapy before escalation of the dose. Blood samples for serum TOR concentration measurements were taken on days 0 and 7. Specimens of tumor and normal lung tissue of approximately 0.5 g were taken on day 7. The concentrations of TOR and its metabolites were determined in serum, lung, and tumor tissue at different dose levels. Altogether, 12 evaluable patients completed the scheduled treatment. The concentrations measured in serum, lung, and tumor tissue increased along with the dose used, such that the highest TOR values were achieved at 600 mg/day, with mean values being 4.9 mumol/l, 175.0 mumol/g, and 122.7 mumol/g, respectively. The concentrations of TOR and its metabolite N-demethyltoremifene were highest in lung tissue, but the values measured in tumor specimens were also well above the respective concentrations detected in serum samples. The TOR doses of 240 and 480 mg/day were well tolerated. One patient in the group treated at 600 mg/day had to discontinue the treatment because of headache and nausea. TOR given at doses ranging from 480 to 600 mg/day for 7 days will produce serum, lung, and tumor concentrations of the parent drug and its metabolites that have been shown to reverse multidrug resistance of cancer cells in vitro. As the 480-mg/day dose of TOR produced tumor concentrations high enough to reverse multidrug resistance without producing adverse drug reactions, the dose recommended for the foreseen clinical trials in the reversal of multidrug resistance would be 480 mg/day for 7 days.
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PMID:Toremifene concentration and multidrug resistance in lung tumors. 899 22

We reported a case of long survival brain metastasis and meningeal carcinomatosis from lung cancer without radiochemotherapy. A 59-year-old female admitted to our hospital suffered from headache, anorexia and nausea. Papilledema was noticed, and examinations showed a brain tumor in the left parietal lobe and cancer cells in cerebrospinal fluid. Removal of the tumor and ventriculoperitoneal shunt were performed. Pathology showed adenocarcinoma. No neurological deficit was found during the postoperative course and the patient asked for home treatment. She survived for 25 months and spent a useful life in the 15 months after the onset in spite of no radiochemotherapy for meningeal carcinomatosis. In this case, because of the slow progression of the clinical symptoms, it is considered that cancer cells in the cerebrospinal fluid space grow slowly. The first CT and MRI findings of metastatic tumor of this case showed atypical for brain metastasis. Calcifications were found in plain CT and a high intensive tumor in both T1 and T2 weighted images of MRI. Enhancement due to contrast media was very slight in both CT and MRI. We considered that these findings were related to the slow growing of cancer cells.
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PMID:[A slowly progressed case of brain metastasis and meningeal carcinomatosis from lung cancer]. 943 Jan 51

Tropisetron (Navoban") suppresses nausea and vomiting induced by cancer chemotherapy by antagonizing central and peripheral 5-HT3 receptors. In this open-label study, tropisetron was evaluated in 873 patients who were either refractory to antiemetic treatment during previous chemotherapy or at high risk of emesis as a result of current chemotherapy. The most commonly used agents alone or in combination were cyclophosphamide (35%), fluorouracil (30%), carboplatin (24%) and cisplatin (21%). The primary tumors were breast cancer (27%), lung cancer (16%), gynecological cancers (12%) and lymphoma (9%). Tropisetron was administered as a 15 min infusion prior to chemotherapy and an additional oral 5 mg dose was taken by 80% of the patients on subsequent days. During course 1, complete response to tropisetron was obtained in 64% of patients on day 1, 54% on day 2, 63% on day 3, 71% on day 4 and 77% on day 5. Very similar response rates were found for the six chemotherapy courses. There were few failures after complete and partial response, at maximum 3 and 15%, respectively. Moreover, 24-38% of those with partial response and 7-29% of those with failure could achieve a complete response during the following cycle. The treatment was well tolerated, the most frequently reported adverse events being constipation (3.7%) and headache (2.6%).
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PMID:Tropisetron in the prevention of acute and delayed nausea and vomiting over six courses of emetogenic chemotherapy. 984 Jul 22

The main form of chemotherapy for non small cell lung cancer is a multiple combination therapy centered on cisplatin (CDDP). We herein report a case in which a favorable course was obtained for a patient with extremely rare AFP-producing lung cancer by single oral administrations of UFT, following extirpation of brain metastasis. The patient was an 80-year-old male whose main complaints were headache and aphasia. Following close examination, a diagnosis was made of moderately differentiated adenocarcinoma with the primary lesion in S6 of the right lung. A metastatic lesion was found in the left occipital lobe. Blood AFP was an abnormally high 17,000 ng/ml. No tumorous lesions were found in the liver. The brain metastasis were extirpated to alleviate cranial nerve symptoms, and the tissue was found to be the same as that of the primary lesion. AFP staining of the tumor tissue revealed positive cells. Because there was proliferation in the primary tumor following surgery, administration of UFT (300 mg/day Tegafur) was begun. Four weeks later the tumor had begun to shrink, and at 15 weeks was judged to be a partial response. A reduction in AFP was also seen. The patient showed absolutely no side effects from UFT, thus enabling outpatient treatment. Good results were obtained both in reducing the tumor and in maintaining the patient's quality of life.
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PMID:[Effective treatment of AFP-producing lung cancer with UFT]. 1006 6

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

Intrathecal administration of 5-fluoro-2'-deoxyuridine (FdUrd) was performed in patients with meningeal dissemination of malignant tumors during the period from January 1996 to September 1998, and they were followed up until February 1999. The study population consisted of 23 patients: 12 with lung cancer, 4 with breast cancer, 2 with colon cancer, 1 with malignant lymphoma, 2 with glioblastoma and 2 with metastatic brain tumors of unknown origin. FdUrd was administered intrathecally through an Ommaya reservoir placed in the lateral ventricle initially at a dose of 1 microg twice per week, and the dose was increased to 10 microg and administration schedule was also increased every day. Headache and nuchal pain were relieved in all patients regardless of responsiveness to intrathecal FdUrd therapy as determined from the findings in the cerebrospinal fluid (CSF). Patients showed no side effects during the course of intrathecal chemotherapy except for slight nausea in two patients and dull headache in one. Sixteen of the 23 patients showed decreased cell number in the cerebrospinal fluid (CSF). Positive cytological findings in CSF became negative in 6 of the 23 patients, and the levels of CSF tumor markers were decreased in 14. Responsiveness to intrathecal administration of FdUrd was defined as 'response' when both the cell number and tumor markers were decreased in both ventricular and spinal CSF or when the cell number was decreased in cases in which the tumor markers were not detected. Overall, 16 of the 23 patients (70%) showed complete or partial responses to intrathecal FdUrd therapy as determined from CSF findings. These results demonstrated the efficacy of intrathecal FdUrd chemotherapy without apparent neurotoxicity for treatment of meningeal dissemination of malignant tumors.
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PMID:Clinical trial of intrathecal administration of 5-fluoro-2'-deoxyuridine for treatment of meningeal dissemination of malignant tumors. 1077 33

We report three cases of meningeal carcinomatosis that metastasized from lung cancer. The patients were men of 73, 65 and 77 years old. The histological type was adenocarcinoma in all cases. At the time of emergence of neurological symptoms such as nausea, headache and cataplexy, enhanced CT of the brain did not disclose brain metastasis. Although brain MRI failed to detect abnormal meningeal findings in cases 1 and 2, meningeal carcinomatosis was diagnosed by cerebrospinal fluid cytology in all three cases. As for treatment, in case 1, methotrexate and prednisolone were administered intrathecally, while the optimum supportive care was given in cases 2 and 3. Because it is difficult to detect meningeal carcinomatosis by brain CT and MRI alone, careful neurological observation and cerebrospinal fluid cytology are necessary for its diagnosis.
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PMID:[Three cases of metastatic meningeal carcinomatosis from lung cancer]. 1232 39

Facial pain can, on rare occasions, be the presenting symptom of lung cancer. This report describes a patient with non-metastatic lung cancer, which was associated with attacks of debilitating facial pain, presenting as cluster headache. Moreover, 32 reported cases of lung cancer-related facial pain (including the present one) are reviewed, and their clinical features are summarized. The facial pain is almost always unilateral, and is most commonly localized to the ear, the jaws, and the temporal region. The pain is frequently described as severe and aching, and may be continuous or intermittent. Aggravation and expansion of the pain, digital clubbing, increased erythrocyte sedimentation rate, and hypertrophic osteopathy, may contribute to the diagnosis. Referred pain, due to invasion or compression of the vagus nerve, as well as paraneoplastic syndrome secondary to the production of circulating humoral factors by the malignant tumor cells, is implicated in the pathophysiology of facial pain associated with non-metastatic lung cancer. Radiotherapy and tumor resection with vagotomy are very effective in aborting the facial pain. Thus, lung cancer should be included in the differential diagnosis of facial pain that is atypical and/or refractory to treatment.
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PMID:Facial pain as first manifestation of lung cancer: a case of lung cancer-related cluster headache and a review of the literature. 1455 96

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

Although the introduction of third-generation antineoplastic agents in the treatment of non-small cell lung cancer has led to modest improvements in overall patient survival, lung cancer continues to be the leading cause of cancer-related death worldwide, and improved therapies are needed. Retinoids play a critical role in the regulation of cell division, growth, differentiation, and proliferation, and they represent an exciting new avenue for targeted therapy. Several synthetic retinoids that bind to retinoic acid receptors are currently being investigated in a variety of tumor types. However, many of these agents have been associated with cheilitis, skin reactions, severe headache, and hypertriglyceridemia. Synthetic agents that bind specifically to retinoid X receptors are called rexinoids. Bexarotene (Targretin; Ligand Pharmaceuticals; San Diego, CA; http://www.ligand.com) is a novel, multitargeted synthetic rexinoid that is currently being investigated in the treatment of non-small cell lung cancer. Phase I and II studies have demonstrated that bexarotene is safe and well tolerated in this patient population either alone or in combination with chemotherapeutic agents. Patients treated with bexarotene experience manageable adverse events at reduced levels compared with retinoic acid receptor-specific retinoids. Bexarotene in combination with chemotherapeutic agents has demonstrated an encouraging median survival for patients with advanced non-small cell lung cancer compared with historical results with combination chemotherapy alone. Two phase III trials are currently under way to fully characterize the role of bexarotene in the treatment of this disease. The purpose of this review is to explore the rationale for rexinoids in the treatment of malignancies and to discuss the clinical profile of bexarotene in the treatment of non-small cell lung cancer.
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PMID:Emerging role of rexinoids in non-small cell lung cancer: focus on bexarotene. 1563 50


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