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)

Efaproxiral [RSR 13, GSJ 61, JP 4, KDD 86, RS 4] is a synthetic, small-molecule, radiation-sensitising agent being developed by Allos Therapeutics primarily for the treatment of cancer. It works by binding and allosterically stabilising deoxyhaemoglobin in hypoxic regions of tumour tissue. This increases oxygen uptake of the tumour tissue and restores its sensitivity to radiation therapy, making therapy potentially more successful. This first-of-its-class compound is particularly applicable for the treatment of certain tumour types that lack oxygen, such as brain metastases. In contrast to conventional chemotherapeutic agents or radiation sensitisers, there is no requirement for efaproxiral to be administered directly into tumours or to cross the blood-brain barrier for it to display efficacy. Efaproxiral is under review for approval in the US and EU as an adjunct to whole-brain radiation therapy (WBRT) for the treatment of brain metastases originating from breast cancer. It is also under clinical evaluation for a variety of other cancers, including glioblastoma, non-small cell lung cancer (NSCLC) and cervical cancer. Allos is seeking partnership opportunities for efaproxiral's development and marketing. The company has indicated that the development of efaproxiral would be in cooperation with a corporate partner, according to its 2003 Annual Report. In 1994, Allos Therapeutics acquired exclusive worldwide rights to intellectual property relating to efaproxiral from the Center for Innovative Technology (CIT). Allos has entered into arrangements with two contract manufacturers for the supply of efaproxiral, and a third manufacturer for the supply of the formulated drug product. Hovione FarmaCiencia is the primary supplier of efaproxiral, and is contracted to manufacture sufficient quantities on a commercial scale. In addition, a second manufacturer, Raylo Chemicals, is also producing quantities of efaproxiral. In December 2003, Allos entered into a long-term development and supply agreement with Baxter Healthcare who will formulate the efaproxiral into an injection. Allos is also seeking to establish an alternate supplier of efaproxiral injection. Allos submitted a rolling NDA to the US FDA consisting of three data components. Submission began in the third quarter of 2003 and was completed by the fourth quarter of 2003. The first part of the application containing non-clinical information was submitted on 5 August 2003. The second part of the NDA containing information about efaproxiral's chemistry, manufacture and controls (CMC) was submitted in October 2003. Allos submitted its final component of the rolling NDA in December 2003. In February 2004, Allos announced that the FDA had accepted the company's NDA under priority review status. The FDA granted efaproxiral orphan drug status in August 2004 as an adjunct to WBRT for the treatment of brain metastases among breast cancer patients. Efaproxiral also received fast-track status in November 2000 for the same indication in the US. In February 2004, Allos initiated a phase III trial, called ENRICH (Enhancing Whole Brain Radiation Therapy In Patients with Breast Cancer and Hypoxic Brain Metastases) to investigate efaproxiral as an adjunct to WBRT for the treatment of brain metastases. Median survival time is the primary endpoint of the study. The National Breast Cancer Coalition (NBCC) is collaborating with the company to support trial enrolment and to gain additional insight about ways to improve radiation treatment in this patient population. The ENRICH trial protocol was approved by the FDA under a Special Protocol Assessment process; as part of the protocol, two interim analyses for safety and efficacy will be performed.This multicentre, randomised, open-label study has a target enrolment of approximately 360 patients at >100 medical centres across the US, Canada, Europe and South America. Allos announced in September 2004 that recruitment of clinical sites for the trial is ongoing across the US and Canada. Completion of trial enrolment in North America is anticipated in December 2005. Subsequently, Allos announced in January 2005 that recruitment into the ENRICH trial has commenced and is ongoing in Europe; enrolment at European sites is expected to conclude by the third quarter of 2006. Allos Therapeutics announced in June 2004 that it had filed an MAA with the EMEA for marketing of exaproxiral as an adjunct to WBRT for treatment of patients with brain metastases originating from breast cancer. The application is based on positive data from a pivotal phase III (REACH, RT-009) trial in this indication. The completed REACH trial investigated efaproxiral among patients with brain metastases undergoing WBRT. The trial was conducted at multiple sites in 11 countries, including the US, Canada, Europe and Australia. In August 2002 Allos completed the enrolment of 538 patients in the study. Initially only 408 patients were to be enrolled, but the company increased the size of the trial to conduct an appropriately powered subgroup analysis in patients with brain metastases from breast and NSCLC. The study was designed to demonstrate a 35% increase in median survival in the subgroup of patients compared with standard WBRT alone. The primary endpoint was survival. Allos began screening US patients for a phase III trial in NSCLC in early 2003. However, in May 2003, the company announced that as part of its revised operating plan it had suspended the screening of patients for this trial. The trial, which was known as ELITE (Enhanced Lung cancer treatment with Induction chemotherapy and Thoracic radiation and Efaproxiral), was comparing induction chemotherapy followed by thoracic radiation therapy with supplemental oxygen, with or without efaproxiral. The trial was enrolling patients with locally advanced, unresectable NSCLC. ELITE was planned to enrol up to 600 patients across North America and Western and Eastern Europe. Phase II trials in patients with inoperable NSCLC have been conducted in the US and Canada. Patient enrolment in one of these studies was completed in August 2000, with a total of 52 patients enrolled. This was an open-label, multicentre study of induction therapy with paclitaxel plus carboplatin followed by chest irradiation and efaproxiral in patients with locally advanced NSCLC. Positive results from this study were reported at the annual meeting of the European Society for Therapeutics Radiology and Oncology in September 2002. Efaproxiral has completed phase I trials as a treatment of surgical hypoxia in elective surgery patients receiving general anaesthesia. However, no recent development has been reported for these indications. In 1994, Allos signed an agreement with CIT for the exclusive worldwide rights to 17 US patents, a European patent covering the UK, France, Italy and Germany plus two pending patents in these territories, two issued patents in Japan, and a pending patent in Canada. These patents cover methods of allosterically modifying haemoglobin with efaproxiral and other compounds, the binding site of efaproxiral and therapy in certain indications including cancer, ischaemia and hypoxia. In addition to the licensed patents from CIT, Allos exclusively owns two patent families with pending applications directed to a formulation of efaproxiral and to methods of its use in BLOD MRI (blood oxygenation level-dependent magnetic resonance imaging) applications. These patents are pending in the US, Canada and Europe, and include an international patent application. In a May 2002 interview with the Wall Street Transcript, the CEO of Allos estimated the overall market for radiation therapy to be approximately 750 000 patients/year. Of this, brain metastases, NSCLC and glioblastoma therapy accounts for about 170 000, 140 000 and 6000 patients, respectively. Allos intend to use a speciality sales force to market efaproxiral directly to radiation therapists in North America. To penetrate the non-oncology market in the US, the company will seek partnership with one or more pharmaceutical companies with direct sales forces and with established distribution systems. Allos is also hoping to secure an oncology marketing partner for non-North American territories. At the time, the company had been issued 21 patents in the US, Canada, Europe and Japan.
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PMID:Efaproxiral: GSJ 61, JP 4, KDD 86, RS 4, RSR 13. 1586 22

A 69 year-old man developed sudden-onset multidirectional, constant, involuntary ocular movements associated with vertigo, truncal ataxia and involuntary movements of the lower limbs. These features were typical of opsoclonus-myoclonus-ataxia syndrome (OMS). MRI of the brain was normal. CSF studies showed a single oligoclonal IgG band. A chest x-ray showed a 2-centimeter lesion in the periphery of the left lung. Fine needle aspiration biopsy of this lesion revealed large B-cell lymphoma. OMS can be either idiopathic or a paraneoplastic manifestation of underlying malignancy. 20 of OMS cases are paraneoplastic in origin; breast and lung cancer are responsible for 70 of these. Association of this syndrome with non-Hodgkins lymphoma is rare, with only one case previously reported.
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PMID:Paraneoplastic Opsoclonus-Myoclonus Syndrome: initial presentation of non-Hodgkins lymphoma. 1593 16

Current imaging modalities fail to define precisely the extent of disease in MPM and are inaccurate in selecting patients for treatment. Previous studies have shown that CT and MRI provide anatomical information that is often imprecise in the preoperative staging of MPM. Consequently, about 25% of patients are found to have unresectable tumor at the time of exploratory thoracotomy. PET is now widely recognized as an important staging modality in many cancers, and PET SUV is reported as a prognostic indicator in several malignancies. However, only a few previous studies have investigated the utility of FDG PET scan in MPM. From 1998 to 2003, 65 patients with MPM underwent PET scans. Median PET SUV in the primary tumor was 6.6 (range, 2-23). The median follow-up for all surviving patients was 16 months. Median survivals were 14 and 24 months for the high and low SUV groups, respectively. In a multivariable analysis, high SUV tumors were associated with a 3.3 times greater risk of death than low SUV tumors (p = 0.03). Mixed histology carried a 3.2 times greater risk of death than epithelial histology (p = 0.03). SUV of >4 and mixed histology are poor risk factors in malignant pleural mesothelioma. These findings suggest that FDG-PET can be used to stratify patients for treatment and clinical trials.
Lung Cancer 2005 Jul
PMID:The role of PET in the surgical management of malignant pleural mesothelioma. 1595 Jul 96

We report 4 cases of spinal cord metastases of lung cancer detected by MRI. Histologically, 3 of the 4 cases were small cell carcinoma and the other was adenocarcinoma. All 3 cases of small cell carcinoma had neoplastic meningitis. MRI taken in these cases showed the multiple nodules in the cauda equina, which were seeded from brain metastases. One of them had intramedullary spinal cord metastases, which appeared as enlargement of the spinal cord or nodules in the spinal cord on MRI. Leg paralysis and incontinence progressed in all cases. The other case of adenocarcinoma had epidural spinal cord compression due to spinal metastasis. In this case irradiation and corticosteroids relieved her leg and back pain. Spinal cord metastases should be considered as a differential diagnosis in patients with numbness, pain or weakness in the extremities.
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PMID:[Spinal cord metastases in lung cancer: a clinical review of four cases]. 1596 11

We report FDG PET of two cases of cold abscess due to Mycobacterium tuberculosis. Case 1 had colon cancer; FDG PET showed high FDG uptake in the colon lesion and low uptake in the inguinal lesion. The latter was a tuberculous cold abscess confirmed by CT/MRI and biopsy. Case 2 received radiotherapy for lung cancer and presented with suspected vertebral metastasis. Further studies revealed tuberculosis of the vertebra and a tuberculous cold abscess in the iliopsoas muscle. FDG PET showed moderate uptake in the third lumbar spine and low uptake in the abscess center of iliopsoas lesion. Both tuberculous cold abscesses showed moderate FDG uptake in the capsule and low uptake in the center. These features are unique compared with non-tuberculous abscess and typical tuberculosis lesions, which are characterized by high FDG uptake. Pathologically, tuberculous cold abscess is not accompanied by active inflammatory reaction. Our findings suggested that the FDG uptake by tuberculous lesion varies according to the grade of inflammatory activity. The new diagnostic features of tuberculous cold abscess may be useful in the evaluation of such lesions by FDG PET.
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PMID:Cold tuberculous abscess identified by FDG PET. 1624 90

To our knowledge, no report exists of a subcentimeter size large cell neuroendocrine carcinoma (LCNEC) of the lung. A 75-year-old man participating in a low-dose CT screening program for lung cancer was found incidentally to have a partly-solid nodule in the right upper lung. After treatment with antibiotics, a repeat CT showed resolution of the nodule, but a new solid nodule measuring 9 x 9 mm was detected in the left lower lobe. The lesion showed marked enhancement on dynamic contrast-enhanced MRI. Video-assisted thoracic surgery and frozen section biopsy was suggestive of malignant lesion, resulting in extension of surgery to lobectomy with nodal dissection. The final diagnosis was stage IA-LCNEC. The estimated volume doubling time of the tumor was 30.1 days. These aggressive tumors may rarely have doubling times that overlap with benign processes.
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PMID:Subcentimeter large cell neuroendocrine carcinoma of the lung. 1628 7

EKB-569 is a potent, low molecular weight, selective, and irreversible inhibitor of epidermal growth factor receptor (EGFR) that is being developed as an anticancer agent. A phase 1, dose-escalation study was conducted in Japanese patients. EKB-569 was administered orally, once daily, in 28-day cycles, to patients with advanced-stage malignancies known to overexpress EGFR. Two patients with advanced non-small cell lung cancer with EGFR mutations and acquired gefitinib resistance from the phase 1 study are described in detail. Case #1 is a 63-year-old man with smoking history. He received treatment from 4 March 2004. Because he had no severe adverse events, a total of 10 courses of therapy were completed through December 16. Grade 2 skin rash and ALT elevation, and grade 1 diarrhea and nail changes developed. A chest CT scan on 4 August 2003 revealed multiple pulmonary metastases that had decreased in size. Case #2 is a 49-year-old woman with no smoking history. She received therapy from 9 February 2004. She received a total of five courses of the therapy until 22 June 2004. Grade 3 nausea and vomiting and grade 1 diarrhea and dry skin developed. A chest CT scan on March 3 revealed multiple pulmonary metastases that had decreased in size. A brain MRI on March 4 showed that multiple brain metastases also had decreased in size. Based on RECIST criteria, they had stable disease but radiographic tumor regression was observed.
Lung Cancer 2006 Mar
PMID:EKB-569, a new irreversible epidermal growth factor receptor tyrosine kinase inhibitor, with clinical activity in patients with non-small cell lung cancer with acquired resistance to gefitinib. 1636 94

Cerebral metastases are a frequent complication of lung cancer. They often determine patients' prognosis and need urgent therapeutic intervention. Based on histologic type, former therapies, age and performance of the patient, the number of cerebral lesions and the extracerebral tumour activity, individualized treatments are applied. For patients who suffer from non-small cell lung cancer and a single CNS lesion the best results can be achieved if they are surgically resected or receive radiosurgery. Their survival time can be markedly increased in comparison to patients who undergo whole brain irradiation. If multiple metastases are seen in CT or MRI, whole brain irradiation is the therapy to choose. Furthermore it should be initiated if small cell lung cancer metastasizes to the brain. More aggressive local treatment options appear promising, but a clear role for them has not yet been defined. Systemic chemotherapy gains more attention in the treatment of small and non-small cell lung cancer with brain metastases. How to increase the efficacy through simultaneous application of chemo- and radiotherapy is tested in current trials. This article gives an overview on clinical presentation and diagnosis of cerebral metastases in lung cancer and reviews current treatment options.
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PMID:[Brain metastases of lung cancer]. 1642 40

Intramedullary spinal cord metastases (ISCM) are usually the result of rapidly progressing systemic malignancy. Lung cancer represents the most common solid tumor associated with the development of ISCM. We describe a 47-year-old female with atypical small cell lung cancer (SCLC) developing ISCM. After a thoracoscopic biopsy she was treated with combination chemotherapy consolidated by mediastinal radiotherapy leading to complete remission. Three months later, she developed a Brown-Sequard syndrome and an MRI scan revealed ISCM at the T10-T12 levels, and secondary brain lesions. Despite treatment with steroids and thoracic spine/brain radiotherapy, no recovery of her motor function was seen and she died 4 months later due to progressive disease in the CNS. The present case, adds to the existing list of ISCM cases reported so far for lung cancer, undermine the ominous prognosis and limited treatment options available, and an extensive literature overview and discussion of similar cases is provided.
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PMID:Intramedullary spinal cord metastases from atypical small cell lung cancer: a case report and literature review. 1646 92

Lung cancer is the leading cause of death among cancers. Early detection and diagnosis present a major goal in the efforts to improve survival rates of lung cancer patients. Changes in angiogenic activity and microvascular perfusion properties in cancers can serve as markers of malignancy. The aim of this study was to employ MRI means to measure the microvascular perfusion parameters of orthotopic nonsmall cell lung cancer, using the experimental rat model. Anatomical and dynamic contrast-enhanced lung images were acquired at high spatial resolution, and registered and analyzed, pixel by pixel and globally, by means of a model-based algorithm. The MRI output yielded color-coded parametric images of the influx and efflux transcapillary transfer constants that indicated rapid microvascular perfusion. The transfer constants were about 1 order of magnitude higher than those found in other tumors or in nonorthotopic lung cancer, with the influx constant median value of 0.42 min(-1) and the efflux constant median value of 1.61 min(-1). The rapid perfusion was in accord with the immunostaining of the capillaries, which suggested the tumor exploitation of the existing alveolar vessels. The results showed that high resolution, dynamic, contrast-enhanced MRI is an effective tool for the quantitative measurement of spatial and temporal changes in lung cancer perfusion and vasculature.
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PMID:Vascular perfusion of human lung cancer in a rat orthotopic model using dynamic contrast-enhanced magnetic resonance imaging. 1647 Aug 42


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