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)

Approximately 30-40% of non-small cell lung cancer patients will present with metastatic disease, and its associated poor prognosis. Chemotherapy has an established palliative role within late-stage disease, but is also being used increasingly in the neoadjuvant and adjuvant settings. Platinum-based chemotherapy has been shown to produce definite improvements in efficacy and quality of life in non-small cell lung cancer patients, and is now the standard of care. Carboplatin has similar biochemical properties to those of cisplatin. However, carboplatin has much less renal, otologic, neurologic and upper gastrointestinal toxicities than cisplatin, and treatment can be conveniently delivered in an out-patient setting. Furthermore, platinum combinations with third-generation cytotoxics have shown additional gains in survival rates. Gemcitabine and carboplatin is a well-tolerated regime. Recent meta- and cost analyses have discovered that gemcitabine-based regimes may have an advantage over other third-generation agent platinum combinations. This article reviews the evidence demonstrating that gemcitabine-carboplatin is effective, convenient and cost effective.
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PMID:Gemcitabine and carboplatin: is this the best combination for non-small cell lung cancer? 1644 69

Lung cancer is one of the most common solid tumors to develop metastases to bone. The prognosis of patients with metastatic lung cancer to bones is short,usually less than 6 months. The treatment requires a multidisciplinary approach that addresses radiotherapy, surgery, chemotherapy, and medical therapy with analgesics and bisphosphonates. Radiotherapy for metastatic bone tumor is a mainstay to relieve pain and control the localized disease. Doses in the range of 20 Gy in 5 fractions, 30 Gy in 10 fractions are acceptable in most circumstances. Prophylactic fixation for long bone fractures is recommended in cases where 30 to 50% of the cortex has been destroyed, pain is present after radiotherapy, or life expectancy is more than 3 months. Systemic chemotherapy has been proved to prolong survival of patients with metastatic non-small-cell lung cancer (NSCLC) as well as extensive small cell lung cancer (SCLC). Combination chemotherapy of platinum and a new drug is recommended in NSCLC patients with good performance status (PS). Gefitinib in upfront or second-line treatment is an optional therapy in adenocarcinoma patients without a history of smoking. Cisplatin combined with etoposide or irinotecan is a standard therapy in SCLC patients with PS 0 or 1. Carboplatin and etoposide is a treatment of choice in SCLC patients with PS 2 or 3. Medical management of cancer pain requires nonsteroidal anti-inflammatory drugs and opioids. Cancer pain that necessitates more than 120 mg of oral morphine is morphine-resistant pain and requires some adjuvant drugs such as corticosteroids, ketamine,anticonvulsants, or local anesthetics. The third generation bisphosphonate zoledronate has been demonstrated to improve cancer pain and to prevent skeletal morbidity in lung cancer patients with metastatic bone disease.
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PMID:[Lung cancer with bone metastasis]. 1691 19

The prognosis of rhabdomyosarcoma (RMS) in advanced stages is still sobering. Therapy is limited due to local tumor recurrence, development of metastases and multidrug resistance. The aim of this study was to investigate the development of multidrug resistance in cell lines and in xenografts of alveolar and embryonal RMS treated according to the German Soft Tissue Sarcoma Study (CWS). Alveolar and embryonal RMS cell lines were treated with Vincristine, Topotecan, Carboplatin, Actinomycin D, or Ifosfamide. Expression levels of resistance-associated genes were assessed using Real time-PCR. Nude mice (NMRI nu/nu, n = 10 per group) underwent xenotransplantation of human embryonal or alveolar RMS. Animals were treated with standard chemotherapeutic drugs Vincristine, Topotecan, Carboplatin, Actinomycin D, or Ifosfamide according to treatment schedules of the CWS-study. Tumor sizes were measured and relative tumor volumes were calculated. Animals were sacrificed after 20 days and standard histology, Real-time-PCR for MDR1-, MRP-, LRP- and MDM2-gene as well as immunohistochemistry for MDR1-, LRP-, and MRP-protein were performed. In the cell lines, an up-regulation of MDR-1 gene was found in alveolar rhabdomyosarcoma. In embryonal rhabdomyosarcoma, an up-regulation of LRP and MRP was found. Standard chemotherapy of alveolar rhabdomyosarcoma resulted in a significant reduction of tumor growth (P < 0.05) in all groups. In embryonal rhabdomyosarcoma strongest effects were found after treatment with Ifosfamide, Vincristine and Carboplatin (P < 0.05). RT-PCR revealed a MDR1-dependent mechanism in alveolar rhabdomyosarcoma. In embryonal rhabdomyosarcoma, MDR1 occurred to a lower degree. Immunohistochemistry revealed correlating expression levels of multidrug resistance-associated proteins. The use of established chemotherapy on human RMS in vivo had strong effects on xenografts compared to their controls. In all cases, there was only a reduction of tumor growth, but not a complete eradication of the tumors. Chemotherapy seemed to upregulate the expression of resistance-associated genes in vitro and in vivo. The mechanism of multidrug resistance depends on the tumor subtype. Therefore, further investigations will be required to evaluate multidrug resistance in patients and to investigate new modalities for a reversal of multidrug resistance.
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PMID:Effects of standard chemotherapy on tumor growth and regulation of multidrug resistance genes and proteins in childhood rhabdomyosarcoma. 1721 91

We report a case of postoperative multiple pulmonary metastases of NSCLC successfully treated with S-1. A 72-year-old man underwent rt. lower lobectomy + ND 2 a by VATS. The histopathological examination showed squamous cell carcinoma, pT4 (satellite nodules in same lobe) N0M0. Multiple pulmonary metastases appeared 3 months after operation. We started combination chemotherapy with S-1 and CBDCA. S-1 (100 mg/body) was administered on days 1-21. CBDCA (AUC=5.0) was administered on day 8. Multiple pulmonary metastases almost disappeared after 2 courses of combination chemotherapy. After 6 courses of combination chemotherapy with S-1 and CBDCA, we then converted to S-1 only. Every cycle was repeated every 5 weeks. One year later, there was no sign of disease progression. S-1 is considered to be effective and safely administered in patients with NSCLC.
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PMID:[A case of postoperative multiple pulmonary metastases of non-small-cell lung cancer successfully treated with S-1]. 1749 52

A non-smoker young man presented to the ophthalmologist with loss of vision in his left eye. Clinical work-up revealed metastatic deposits in left retina. Broadened workup also showed metastatic disease in the skull and brain. The search for the primary concluded on the histopathological evidence of Non-Small Cell Lung Carcinoma (NSCLC) in the upper lobe of the left lung. After the diagnosis and ascertaining disease extent, localized radiotherapy to whole skull and retina was given, followed by conventional chemotherapy (Gemcitabine, Carboplatin). The results of radiation and chemotherapy were not satisfactory, therefore, patient was placed on a new agent (tyrosine kinase inhibitor) Erlotinib (150 mg per day orally in a single dose). The response was evaluated using clinical and radiological parameters and was found to be satisfactory.
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PMID:Unilateral blindness as a presenting symptom of lung cancer treated with erlotinib. 1845 5

Combined modality treatment for esophageal carcinoma seems to improve survival over surgery alone. Different combinations of cytotoxic drugs have been studied to improve antitumor efficacy and limit the toxicity of chemoradiotherapy (CRT) with inconsistent results. We present a prospective study of neoadjuvant CRT with or without paclitaxel in chemotherapy schedule. One hundred seven patients (93 males, 14 females), median age 59 years (range 44-76), with operable esophageal cancer were enrolled. They received the following neoadjuvant therapy: Carboplatin, area under curve (AUC) = 6, intravenously on days 1 and 22, 5-fluorouracil (5-FU), 200 mg/m(2)/day, continuous infusion on days 1 to 42, radiation therapy 45 grays/25fractions/5 weeks beginning on day 1. Forty-four patients (41%) were furthermore non-randomly assigned to paclitaxel 200 mg/m(2)/3 h intravenously on days 1 and 22. Nutritional support from the beginning of the treatment was offered to all patients. Surgery was done within 4-8 weeks after completion of CRT, if feasible. All patients were evaluated for grade 3 plus 4 toxicities: leukopenia (28%), neutropenia (30%), anemia (6%), thrombocytopenia (31%), febrile neutropenia (6%), esophagitis (24%), nausea and vomiting (7%), pneumotoxicity (8%). Seventy-eight patients (73%) had surgery and 63 of them were completely resected. Twenty-two patients (20%) achieved pathological complete remission, and additional 20 (19%) had node-negative and esophageal wall-positive residual disease. There were 10 surgery-related deaths, mostly due to pulmonary insufficiency. Twenty-nine patients were not resected, 15 for early progression, 14 for medical reasons or patient refusal. After a median follow-up of 52 months (range 27-80), median survival of 18.0 months and 1-, 2-, 3- and 5-year survival of 56.7, 37.5, 27.0 and 21% was observed in the whole group of 107 patients. Addition of paclitaxel to carboplatin and continual infusion of FU significantly increased hematologic and non-hematologic toxicity, but treatment results as overall survival or time to progression did not differ significantly in groups with and without paclitaxel. Patients achieving pathological complete remission or nodes negativity after neoadjuvant therapy had favorable survival prognosis, whereas long-term prognosis of node positive patients was poor. Distant metastases prevailed as a cause of the treatment failure. Factors significant for survival prognosis in multivariate analysis were postoperative node negativity, performance status, and grade of dysphagia. Addition of paclitaxel to carboplatin and continual FU significantly increased hematologic and non-hematologic toxicity without influencing efficacy of the treatment. This study confirmed improved prognosis of patients after achieving negativity of nodes. Distant metastases prevailed as cause of the treatment failure. Prospectively, it is important to look for a therapeutic combination with better systemic effect.
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PMID:Prospective non-randomized study of preoperative concurrent platinum plus 5-fluorouracil-based chemoradiotherapy with or without paclitaxel in esophageal cancer patients: long-term follow-up. 1951 90

There is at present no defined role for S-1 chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who previously failed chemotherapy. Two cases of multidrug-resistant, NSCLC that were successfully treated with S-1 as fifth-line chemotherapy are reported. A 75-year-old man was diagnosed as having pulmonary adenocarcinoma, cT1N3M0, stage III B. He was treated with S-1 as fifth-line chemotherapy after treatment with cisplatin(CDDP)and vinorelbine(VNR), docetaxel (DOC), gemcitabine (GEM) and VNR, and amrubicin (AMR). After completing two courses, chest computed tomography(CT)showed a partial response( PR)of the recurrent tumors, and the serum carcinoembryonic antigen level decreased. Currently, seven courses have been completed, and this treatment will be continued due to the tumor response of stable disease. A 65-year-old woman was referred for treatment of recurrent pulmonary adenocarcinoma after right upper lobe resection. She was treated with S-1 as fifth-line chemotherapy after treatment with GEM and VNR, carboplatin(CBDCA) and paclitaxel ( PTX), DOC, and gefitinib. After completing five courses, chest CT showed PR of the intrapulmonary metastases. Though grade 3 toxicity-anemia in the first case and an elevated serum amylase level in the second case were observed in both cases, the patients' quality of life was preserved. S-1 could therefore be a treatment option for patients with advanced NSCLC who previously underwent chemotherapy unsuccessfully.
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PMID:[Two cases of recurrent non-small cell lung cancer successfully treated with S-1 as fifth-line chemotherapy]. 1983 34

BACKGROUND: Adjuvant 5-fluorouracil (5FU)-based chemo-radiotherapy is currently considered a standard of care for the treatment of gastric cancer. The impact of 5FU-based adjuvant therapy on the rate of distant recurrence has been modest. In order to improve the systemic effects of adjuvant therapy, we have been treating patients with resected gastric cancer with carboplatin and paclitaxel followed by fluoropyrimidine analogue and radiation. METHODS: We report on the outcomes of 21 consecutive gastric cancer patients treated off protocol with adjuvant carboplatin (area under the curve 5 mg/ml x min) and paclitaxel (175-200 mg/m(2)) every 3 weeks, followed by concurrent pyrimidine analogs (either capecitabine 1,600-2,000 mg/m(2)/day in 17 patients, or 5FU 200 mg/m(2)/day in 4 patients) and radiation (45-50.4 Gy). Patients received a total of 4-6 cycles of carboplatin and paclitaxel. RESULTS: The median age at diagnosis was 60 years. Sixteen patients had stage 3 disease and 7 of them had positive surgical margins (6 with R1 and 1 with R2 resection), 3 patients were stage 2, and 2 patients were stage 1 (all had R0 resection). All patients had D1/D2 (4 had D2 and 17 had D1) lymph node dissection. The incidence of grade 3 or higher overall, hematologic, or gastrointestinal toxicity in the patients receiving carboplatin and paclitaxel was 57, 48 and 10%, respectively. No treatment-related deaths were observed. After adjuvant treatment 15 patients developed recurrent disease, 10 of whom had distant metastases. The median recurrence-free survival (RFS) was 12.3 months. The median overall survival (OS) was 16.0 months. Patients with R0 resection had significantly longer OS than did those with positive surgical margins (log-rank p = 0.0060). Median OS for the R0 resection group was 28.8 months. CONCLUSIONS: Carboplatin and paclitaxel added to radiation plus fluoropyrimidine analogs is a well-tolerated regimen in the adjuvant setting. The activity of this regimen in this relatively high-risk group of gastric cancer patients is of interest for future development.
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PMID:Safety and Feasibility of Carboplatin and Paclitaxel followed by Fluoropyrimidine Analogs and Radiation as Adjuvant Therapy for Gastric Cancer. 2073 41

Squamous cell carcinoma of the head and neck (SCCHN) presents at a locally advanced (LA) stage in many patients. Chemotherapy, which is one fundamental therapy mode for local disease control of inoperable disease or if organ preservation is desired, has become an important factor of first line treatment regimens either during or prior to radiotherapy (RT). Patients with locoregionally advanced inoperable, recurrent or metastatic disease still have a poor prognosis, which enforces the need for new treatment approaches and new drug therapies, adjusted to the different settings of the disease. One innovative progress for this collective of patients with locally advanced tumor was the implementation of Docetaxel in chemotherapeutic regimes in optimal combination with concurrent chemoradiotherapy or in neoadjuvant setting of induction phase treatment. Docetaxel combined with the conventional chemotherapy regimen, containing Cisplatin and 5-Fluorouracil (TPF), is now acknowledged as being the gold standard of induction treatment. Various studies suggest survival advantage due to the induction chemotherapy (ICT) followed by chemoradiotherapy, which is known as sequential therapy, over chemoradiotherapy alone. In contrast to prevailing studies we administered Docetaxel, Carboplatin and 5-FU within the frame-work of induction chemotherapy instead of conventional use of Cisplatin for five patients with locoregionally advanced HNSCC. The clinical progress was evaluated through cross section imaging (computer tomography/MRI) prior and after ICT and classified following the RECIST criteria. Due to a very small collective of patient and the administration of Carboplatin instead of Cisplatin in this study, it was not possible to document the the efficacy of ICT (TPF) concerning survival advantage in patient with locoregionally advanced head and neck tumors. Further studies with an extended collective of patients are neccessary.
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PMID:Induction chemotherapy with TPF (Docetaxel, Carboplatin and Fluorouracil) in the treatment of locally advanced squamous cell carcinoma of the head and neck. 2087 12

This patient is a male in his 30's. He was diagnosed as hepatitis B virus-related huge primary liver cancer, 10cm in diameter, located in segment 4, accompanied with left portal thrombus and multiple lung metastases. Ten months after repeating systemic chemotherapy using gemcitabine (GEM)+carboplatin (CBDCA)+5-FU/leucovorin (LV) and hepatic arterial infusion chemotherapy with cisplatin (CDDP) 4 times, extended left lobectomy with caudate lobe could be successfully performed because of marked reducion of the huge tumor. The pathology revealed almost entirely necrotic changes of the main tumor, and the remaining, viable tumor nests showed combined hepatocellular and cholangiocarcinoma. Systemic chemotherapy was repeatedly given afterwards, which kept the pulmonary metastases stable without growth. The present case suggests that systemic chemotherapy using GEM+CBDCA+5-FU/LV may be useful in the multimodal treatment for the combined hepatocellular and cholangiocarcinoma with distant metastases.
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PMID:[Effectiveness of systemic chemotherapy of GEM+CBDCA+5-FU/LV and hepatic arterial infusion of CDDP in a case of advanced, combined hepatocellular-cholangiocarcinoma with multiple lung metastases]. 2205 11


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