Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early resection of lung cancers confined to the chest remains the best means of curing patients. Nonetheless, cure rates for resected patients are less than 50% overall, primarily due to the presence of occult distant metastases at the time of resection that subsequently manifest as relapse at distant sites. In approximately 20% of patients, local failure occurs within the chest. Chest radiotherapy reduces and nearly eliminates local failure, but does not improve survival or cure rates. Effective systemic chemotherapy is the cornerstone to improving survival and cure rates for early stage lung cancer. Recent studies showed that the preoperative use of cisplatin-based chemotherapy improved survival and 3-year disease-free survival in stage IIIA non-small cell lung cancer. New drugs such as paclitaxel and gemcitabine appear to improve survival in stages IIIB and IV non-small cell lung cancer. These agents will be tested in the surgical setting in the near future.
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PMID:Systemic investigational therapies as adjuvants to surgery in patients with operable lung cancer. 920 18

In order to explore the activity of a combination of vinorelbine (VNL) and alternating cisplatin (CDDP) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), a phase II study was performed. Seventy chemoradiotherapy naive patients with NSCLC, stage IIIA, IIIB and IV disease, PS (ECOG) </=2, were treated with CDDP 40 mg/m(2) on days 1, 2, 3, IFX 1,800 mg/m(2) on days 22, 23, 24 and VNL 30 mg/m(2) on days 1, 8, 22, 29 every 6 weeks up to 6 courses. In the 67 evaluable patients, an objective response rate was observed in 47.8 +/- 12% (95% CI) with complete responses in 6%; responses occurred more frequently in patients with locally advanced disease (stage IIIA/IIIB) and/or performance status 0. The median duration of survival was 12 months: 19.9 months in stage III patients who received an integrated treatment and 10 months in metastatic disease. The median time to treatment failure was 10.5 months. Toxicity was mainly hematological, even though it was not dose-limiting and easily manageable. This combination seems to be active, and the good safety profile is probably the result of the use of an alternating schedule of CDDP and IFX. Median overall survival was also encouraging in stage IV disease. The prolongation of survival obtained when surgery and/or radiotherapy is applicable needs confirmation through a larger study.
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PMID:Vinorelbine and alternating cisplatin and ifosfamide in the treatment of non-small cell lung cancer. 1064 37

The combination of carboplatin and paclitaxel is an active regimen in non-small cell lung cancer (NSCLC). Historically, patients with stage III disease have manifested higher response rates than patients with metastatic disease, and patients achieving a pathologic complete response to induction chemoradiation therapy prior to surgery have shown better long-term outcome. Based upon our pilot data using high-dose carboplatin and paclitaxel, we designed a phase II trial in patients with marginally resectable stage IIIA NSCLC. Ten patients, with bulky nodal stage IIIA disease, initially received etoposide (2 g/m2) and granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSC). Two cycles, 28 days apart, of carboplatin (AUC 12 in seven patients; AUC 16 in three patients) and paclitaxel (250 mg/m2) were administered with filgrastim (5 microg/kg) and PBSC support. After re-evaluation, patients underwent a thoracotomy followed by radiotherapy (44-60 Gy) if deemed resectable, or radiotherapy alone (60 Gy) if not resectable. The median age was 58.5 years (48-66) with a median ECOG performance status of 0 (0-1). Histology was adenocarcinoma in seven patients; the remainder had either squamous cell, large cell or bronchoalveolar carcinoma. Based on CT radiography, the overall response rate was 40%. Eight of ten patients underwent resection with four right pneumonectomies, three right upper lobectomies and one wedge resection of the right upper lobe. Six patients had a complete resection. Of eight patients resected, four were downstaged by induction therapy, three remained unchanged and one was found to have more extensive disease. The remaining two patients developed metastatic disease while receiving chemotherapy. The median dose of postoperative radiotherapy was 54 Gy (35-66 Gy). Actual median follow-up for all patients was 89 weeks (25 to 136+). The actuarial median overall survival was 124 weeks (25 to 136+) and time to progression was 57 weeks (17 to 136+). The median dose of carboplatin delivered expressed as mg/m2 was 779 (615-1540). Neutropenic fever occurred in two patients during the initial mobilization cycle only. The median number of units of RBC and/or platelets transfused was 0 (0-2 and 0-6, respectively). There were no significant non-hematologic toxicities. High-dose induction chemotherapy with stem cell rescue is feasible and safe with an acceptable response rate. Thoracotomy, including pneumonectomy and postoperative radiotherapy, were well tolerated by patients after undergoing high-dose induction chemotherapy with no apparent increase in peri-operative morbidity. The pathologic complete response rate was low--one out of ten patients. These results indicate that dose escalation of induction chemotherapy does not improve response rates even in this highly selected patient population. Accordingly, the complexity and potential toxicity of high-dose chemotherapy, as delivered in this trial as neoadjuvant treatment of non-small cell lung cancer, is not warranted.
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PMID:Phase II trial of induction high-dose chemotherapy followed by surgical resection and radiation therapy for patients with marginally resectable non-small cell carcinoma of the lung. 1067 82

The resectability of NSCLC is determined by its stage. The surgical treatment in stage I and II NSCLC remains a golden standard. Stage IIIA NSCLC constitutes a non-homogenous group, and many patients are potentially non-resectable. The patients in stage IIIA NSCLC also constitute a non-homogenous group. The patients in stage T3N1 usually undergo surgical resection, but many patients with N2 disease are disqualified from surgical treatment due to the negative prognostic factors. The negative prognostic factors comprise: (1) metastases to upper paratracheal (no 2), anterior paratracheal (no 3), and subcarinal (no 7) lymph nodes; (2) metastases to multiple mediastinal lymph nodes; (3) occurrence of the so called 'bulky disease'; (4) capsular lymph node invasion. The occurrence of one of these negative prognostic factors disqualifies the patient with N2 disease from radical surgical treatment. In more advanced cases, i.e. stage IIIB, and stage IV NSCLC, patients are rarely operated. It regards the patients in stage T4 N1, and in M1 disease with a single metastasis (mainly to CNS) accompanied by the stage I, or II, of the primary focus. In these cases N2 disease always constitutes the contraindication to the surgical treatment. Multidisciplinary approach in the treatment of NSCLC is supposed to improve the results of the treatment of NSCLC.
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PMID:Surgical treatment of stage III non-small cell lung cancer. 1172 Jul 55

We conducted a phase I/II study to investigate whether the surgical resection after induction chemotherapy with cisplatin and irinotecan was feasible and could improve the treatment outcome for patients with pathological N(2) non-small cell lung cancer. Fifteen patients with stage IIIA non-small cell lung cancer having mediastinal lymph node metastases proved by mediastinoscopy were eligible. Both cisplatin (60 mg m(-2)) and irinotecan (50 mg m(-2)) were given on days 1 and 8. Patients received two cycles of chemotherapy after 3-4 weeks interval. Induction was followed by surgical resection in 4-6 weeks. Patients who had documented tumour regression after preoperative chemotherapy received two additional cycles of chemotherapy and other patients received radiotherapy postoperatively. After the induction chemotherapy, the objective response rate was 73%. All the 15 patients received surgical resection and complete resection was achieved in 11 (73%) patients. There was no operation-related death and one death due to radiation pneumonitis during postoperative radiotherapy. The median time from entry to final analysis was 46.5 months, ranging from 22 to 68 months. The 5-year survival rate was 40% for all the 15 patients and it was 55% for the 11 patients who underwent complete resection. We conclude that the surgical resection after induction chemotherapy with cisplatin and irinotecan is feasible, and associated with low morbidity and high respectability.
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PMID:Preoperative induction chemotherapy with cisplatin and irinotecan for pathological N(2) non-small cell lung cancer. 1187 May 32

Motexafin gadolinium [gadolinium (III) texaphyrin, gadolinium texaphyrin, Gd-Tex, GdT2B2, PCI 0120] is a radiosensitising agent developed for use in cancer therapy. It is cytotoxic in haematological malignancies by selectively localising in cancer cells that have high rates of metabolism. Motexafin gadolinium inhibits cellular respiration resulting in the production of reactive oxygen species and inducing apoptosis. It is being developed by Pharmacyclics in the US. Bulk motexafin gadolinium is supplied to Pharmacyclics by the US company, Celanese, through a manufacturing and supply agreement between the two companies. In June 2003, at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO-2003), the importance of having an agent for the treatment of brain metastases from lung cancer was highlighted. Results of a phase III study were presented that showed that motexafin gadolinium treatment was associated with a delay in time to neurological and neurocognitive progression in lung cancer patients. This was an important finding, as 46.6% of lung cancer patients already have brain metastases at the time of initial diagnosis, compared with only 2.7% of breast cancer patients. Brain metastases are also often the only site of metastatic disease in patients with lung cancer. In December 2002, Pharmacyclics began a phase III trial of motexafin gadolinium in patients with brain metastases (brain cancer in phase table) from lung cancer in the US, Europe, Canada and Australia. The trial is known as the Study of neurologic progression with Motexafin gadolinium And Radiation Therapy (SMART) and will compare whole-brain irradiation with whole-brain irradiation plus motexafin gadolinium in 550 patients. The primary efficacy endpoint is time to neurological progression and the secondary endpoints are survival and neurocognitive function. In January 2003, the US FDA completed its Special Protocol Assessment (SPA) of the SMART trial with a positive result and by June 2003, enrollment had begun. In addition, phase I trials are underway in children with intrinsic pontine glioma and adults with head and neck, lung and pancreatic cancers. A phase II trial is also being conducted in the US in patients with glioblastoma multiforme. Enrollment in this trial has been completed and preliminary results have been reported. Pharmacyclics has completed enrollment and follow-up of adults in its pivotal phase III trial of motexafin gadolinium as a radiation sensitiser for the treatment of brain metastases. The trial was conducted at 35 centres in Europe, Canada and the US. Full results from this initial phase III trial were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Florida, USA, held in May 2002. Pharmacyclics also announced in October 2002, at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), that motexafin gadolinium significantly prolonged time to neurological progression when added to whole brain radiation therapy and reduced the number of deaths in patients with brain tumour. Pharmacyclics announced in September 2000 that it has initiated two NCI-sponsored phase I trials conducted under a Cooperative Research and Development Agreement (CRADA) between Pharmacyclics and the NCI. The first trial, conducted in patients with stage IIIA non-small cell lung cancer, was designed to determine the safety of two different dosing regimens of motexafin gadolinium during preoperative radiotherapy after induction chemotherapy. The second study was designed to examine the use of motexafin gadolinium in combination with stereotactic Gamma Knife radiosurgery in patients with primary glioblastoma mutiforme. Two phase I clinical trials have also been conducted for the treatment of newly diagnosed glioblastoma multiforme at the UCLA Jonsson Comprehensive Cancer Center, USA. These phase I studies were sponsored by the NCI and were conducted under a CRADA with the NCI. Pharmacyclics has also completed multicentre US phase II clinical trials of motexafin gadolinium fin gadolinium in patients with metastatic tumours of the brain who require whole brain radiotherapy. Motexafin gadolinium is in a phase II trial in patients with lymphomas and multiple myeloma in the US.
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PMID:Motexafin gadolinium: gadolinium (III) texaphyrin, gadolinium texaphyrin, Gd-Tex, GdT2B2, PCI 0120. 1472 95

Lung cancer remains the leading cause of cancer death in American men and women. Non-small-cell lung cancer (NSCLC) accounts for 85% of these cases. Although surgery is the best curative approach for resectable NSCLC, long-term survival for patients with operable disease remains poor. More than half of patients who initially present with stage I to IIIA disease experience relapse of metastatic disease. Postoperative adjuvant therapy has been evaluated in several randomized trials, and provides a survival benefit. It appears reasonable to look to induction chemotherapy, or preoperative chemotherapy, to provide a similar improvement in survival with early treatment of micrometastatic disease. Multiple trials of induction therapy have been carried out with encouraging results. The use of various induction regimens with chemotherapy alone or chemotherapy combined with radiotherapy for stage IIIA NSCLC is under investigation. Randomized trials are under way to better define the role of induction therapy in the multimodality treatment of NSCLC.
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PMID:Induction chemotherapy for resectable non-small-cell lung cancer. 1564 93

The optimal management of locally advanced, Stage IIIA NSCLC with N2 level nodal metastases remains challenging and controversial. A number of treatment regimens have been shown safe and effective, but existing clinical trial data frequently falls short of providing guidance to match the right approach with the right patient. We review recent literature in this area and its impact.
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PMID:Current readings: management of N2 disease for lung cancer. 2363 Feb 7

The treatments for advanced non-small cell lung cancer (NSCLC) should control both local and microscopic systemic disease, because the 5-year survival of patients with Stage III NSCLC who underwent surgical resection alone has been dismal. One way to improve surgical outcome is the administration of chemotherapy before or after the surgical procedure. During the last two decades, many clinical studies have focused on developing optimal adjuvant or neoadjuvant chemotherapy regimens that can be combined with surgical treatment and/or radiotherapy. Based on the results of those clinical studies, multimodality therapy is considered to be an appropriate treatment approach for Stage IIIA NSCLC patients; although, optimal treatment strategies are still evolving. When N2 nodal involvement is discovered postoperatively, adjuvant cisplatin-based chemotherapy confers an overall survival benefit. The addition of postoperative radiotherapy might be considered for patients with nodal metastases. Although definitive chemoradiation remains a standard of care for cN2 NSCLC, alternative approaches such as induction chemotherapy or chemoradiotherapy and surgery can be considered for a selective group of patients. When surgical resection can be performed after induction therapy with low risk and a good chance of complete resection, the outcome may be optimal. The decision to proceed with resection after induction therapy must include a detailed preoperative pulmonary function evaluation as well as a critical intraoperative assessment of the feasibility of complete resection.
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PMID:Neoadjuvant and adjuvant therapy for Stage III non-small cell lung cancer. 2913 12

Stage III non-small cell lung cancer is a border line stage between localized and metastatic disease. PDL-1 is gaining an important role in the therapeutic arsenal of lung cancer, the most frequent cancer worldwide. We report for the first time a negativation of PDL-1 status in 2 cases of stage IIIA NSCLC with conversion to operable disease after using immunotherapy. The first patient was a 59-year old female diagnosed incidentally to have stage IIIA inoperable NSCLC that was treated with combination chemo-immunotherapy, and converted to operable disease with a negative PD-L1 in the postoperative setting. The second case is that of a 56-year old male that also had an inoperable stage IIIA NSCLC treated with chemotherapy first line followed by pembrolizumab at progression, then operated after surgical conversion, with negative PD-L1 postoperatively. In front of these findings, further work should be done to elucidate if the reverse of the PDL-1 status and the conversion to operability were due to the use of immunotherapy or to an incidental finding. If confirmed, it may have a therapeutic impact.
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PMID:Negativation of PD-L1 Postoperatively in Initially Inoperable Stage III Non-Small Cell Lung Cancer Treated with Pembrolizumab: Two Case Reports. 3124 45


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