Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The class I IgG receptor (Fc gamma RI or CD64 receptor), which is present on key cytotoxic effector cells, has been shown to initiate the destruction of tumor cells in vitro and has been hypothesized to play a role in the destruction of antibody-coated cells such as platelets in idiopathic thrombocytopenia purpura (ITP). This overview summarizes the clinical experience with CD64-directed immunotherapy in cancer patients with the bispecific antibodies MDX-447 [humanized Fab anti-CD64 x humanized Fab anti-(epidermal growth factor receptor, EGFR)] and MDX-H210 (humanized Fab anti-DC64 x Fab anti-HER2/neu), and with the anti-CD64 monoclonal antibody (mAB) MDX-33 (H22) in the modulation of monocyte CD64 in vivo. In an ongoing phase I/II open-label trial with progressive dose escalation (1-15 mg/m2), patients with treatment refractory EGFR-positive cancers (renal cell carcinoma (RCC), head and neck, bladder, ovarian, prostate cancer and skin cancer) are treated weekly with intravenous MDX-447, with and without granulocyte-colony-stimulating factor (G-CSF). MDX-447 has been found to be immunologically active at all doses, binding to circulating monocytes and neutrophils (when given with G-CSF), causing monocytopenia and stimulating increases in circulating plasma cytokines. MDX-447 is well tolerated, the primary toxicities being fever, chills, blood pressure lability, and pain/ myalgias. Of 36 patients evaluable for response, 9 have experienced stable disease of 3-6 month's duration. The optimal dose and the maximal tolerated dose (MTD) have yet to be defined; dose escalation continues to define better the dose, toxicity, and the potential therapeutic role of this bispecific antibody. Three MDX-H210 phase II trials are currently in progress, all using the intravenous dose of 15 mg/m2 given with granulocyte/macrophage (GM-CSF). These consist of one trial each in the treatment of RCC patients, patients with prostate cancer, and colorectal cancer patients, all of whom have failed standard therapy. At the time of writing, 11 patients have been treated in these phase II trials. Four patients have demonstrated antitumor effects. Patients demonstrating responses include 2 with RCC and 2 with prostate cancer. One RCC patient has had a 54% reduction in size of a hepatic metastatic lesion and the other has had a 49% decrease in the size of a lung metastasis with simultaneous clearing of other non-measurable lung lesions. Regarding the two patients with prostate cancer, one has had a 90% reduction in serum prostate-specific antigen (PSA; 118-11 ng/ml), which has persisted for several months; the other patient with prostate has had a 70% reduction of serum PSA (872 ng/ml to 208 ng/ml) within the first month of treatment. Both patients have also demonstrated symptomatic improvement. In a completed phase I and in ongoing phase I/II clinical trials, patients with treatment-refractory HER2/neu positive cancers (breast, ovarian, colorectal, prostate) have been treated with MDX-H210, which has been given alone and in conjunction with G-CSF, GM-CSF, and interferon gamma (IFN gamma). These trials have been open-label, progressive dose-escalation (0.35-135 mg/m2) studies in which single, and more often, multiple weekly doses have been administered. MDX-H210 has been well tolerated, with untoward effects being primarily mild-to-moderate flu-like symptoms. The MTD has not yet been defined. MDX-H210 is immunologically active, binding to circulating monocytes, causing monocytopenia, as well as stimulating increases in plasma cytokine levels. Furthermore, some patients have evidence of active antitumor immunity following treatment with MDX-210. Antitumor effects have been seen in response to MDX-H210 administration; these include 1 partial, 2 minor, and 1 mixed tumor response; 15 protocol-defined stable disease responses have occurred. (ABSTRACT TRUNCATED)
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PMID:Clinical experience with CD64-directed immunotherapy. An overview. 943 76

The proto-oncogene HER2 presents a novel therapeutic target. We report results in 25 patients with HER2+ advanced prostate cancer treated with the bispecific antibody MDX-H210 15 microg m(-2)by intravenous infusion plus GM-CSF 5 microg kg(-1)day(-1)by subcutaneous injection for 4 days repeated weekly for 6 weeks. Patients with stable disease or better received further cycles of treatment until disease progression or study withdrawal. 1 patient received no treatment and 4 received less than 1 cycle and are included in the toxicity analysis only. Median duration of follow up was 105+ (range 21-188) days. Toxicity was generally NCI-CTG 0-2. There were 2 grade 4 adverse events (heart failure and dyspnoea) and 1 grade 3 event (allergic reaction) resulting in discontinuation of the study medication. There were 9 further grade 3 events not resulting in trial withdrawal. There were no treatment-related deaths. 7/20 (35%) evaluable patients had a >50% PSA response of median duration 128 (range 71-184+) days. 7/12 (58%) patients with evaluable pain had improvements in pain scores. The PSA relative velocity on therapy decreased in 15/18 (83%) assessable patients compared to pre-study. GM-CSF and MDX-H210 is active in hormone refractory prostate carcinoma with acceptable toxicity; further studies are warranted.
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PMID:A phase II study of the bispecific antibody MDX-H210 (anti-HER2 x CD64) with GM-CSF in HER2+ advanced prostate cancer. 1146 Oct 69

ScFv(FRP5)-ETA is a recombinant single-chain antibody-toxin with binding specificity for ErbB2/HER2. Previously potent antitumoral activity of the molecule against ErbB2 overexpressing tumor cells was demonstrated in vitro and in animal models. Here we report on the first application of scFv(FRP5)-ETA in human cancer patients summarizing case reports collected in four different clinical centers. Eleven patients suffering from metastatic breast and colorectal cancers and from malignant melanoma were treated on a compassionate-use basis by intratumoral injection of scFv(FRP5)-ETA into cutaneous lesions once daily for 7-10 days. Total daily doses ranged from 60 to 900 microg, and total doses per treatment cycle ranged from 0.6 to 6.0 mg. Treatment caused injected tumors to shrink in six of the 10 cases evaluated (60%). Complete regression of injected tumor nodules was accomplished in four patients (40%) and partial reduction in tumor size in another two patients (20%). Adverse reactions were restricted to local symptoms such as pain and inflammation at injection sites which were fully reversible. Only in one patient treated at the highest daily doses systemic liver toxicity of grade 2 was observed and treatment was discontinued on day 7. No hematologic, renal, and/or cardiovascular toxicities were noted. Our results demonstrate that local therapy with scFv(FRP5)-ETA can be effective against ErbB2 expressing tumors justifying further clinical development of this reagent.
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PMID:Regression of cutaneous tumor lesions in patients intratumorally injected with a recombinant single-chain antibody-toxin targeted to ErbB2/HER2. 1470 62

The human epidermal growth factor receptor (HER) 2 is overexpressed in approximately 20-25% of human breast cancers and is an independent adverse prognostic factor. Targeted therapy directed against this receptor has been developed in the form of a humanised monoclonal antibody, trastuzumab. This antibody has shown activity as a single agent in metastatic breast cancer both prior to chemotherapy and in heavily pretreated patients. A pivotal Phase III trial has demonstrated that its use in combination with an anthracycline or paclitaxel results in a significant improvement in survival, time to progression, and response. This has recently been reinforced by another trial with docetaxel. The HER2 status of a tumour is a critical determinant of response to trastuzumab-based treatment. Those that express HER2 at the highest level on immunohistochemistry (IHC), 3+, derive more benefit from treatment with trastuzumab than those with overexpression at the 2+ level. Benefit correlates best with tumours that are positive on fluorescence in situ hybridisation for HER2, regardless of IHC status. Treatment with trastuzumab is generally well tolerated with a low incidence of adverse events. Some patients may experience fever, chills, dyspnoea and pain, particularly with the first administration. Unexpectedly, cardiac toxicity has developed in some patients treated with trastuzumab, and this has a higher incidence in those treated in combination with an anthracycline. 'Cross-talk' between the oestrogen receptor and HER2 pathway has stimulated interest in using trastuzumab in combination with endocrine therapy. Current clinical trials are investigating the role of this agent in the adjuvant setting.
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PMID:Efficacy and safety of trastuzumab. 1526 49

We report a unique case of adenoid cystic carcinoma (ACC) of the maxillary sinus, with gradual histologic transformation from lower-grade ACC (cribriform and tubular types) to high-grade adenocarcinoma (HGA) showing a sequential histologic spectrum via solid-type ACC. A 74-year-old man presented with swelling and mild pain of the right cheek. CT scan showed a mass measuring approximately 4 cm, with marked bone destruction in the right maxillary sinus. A surgically resected specimen revealed that the tumor was comprised of three different components: HGA and solid-type ACC in the central portion and lower-grade ACC in the periphery. The tumor was discriminated from a dedifferentiated carcinoma or hybrid tumor. Autopsy specimens also demonstrated both solid-type ACC and HGA components in the lung and spleen. Immunohistochemically, positive staining of p53 protein was detected on both solid-type ACC and HGA cells, but cyclin D1 and HER2/neu was only seen in HGA cells. Solid-type ACC cells were immunoreactive for CD117 (c-kit), but lower-grade ACC and HGA cells were negative. This case suggests that the overexpression of CD117, p53 protein, cyclin D1, and HER2/neu might be involved in the progression from lower-grade ACC to solid-type ACC and HGA.
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PMID:Adenoid cystic carcinoma of the maxillary sinus with gradual histologic transformation to high-grade adenocarcinoma: a comparative report with dedifferentiated carcinoma. 1613 59

A-64-year-old woman, who had been treated with augmentation mammaplasty 40 years ago, came to our hospital complaining of left breast pain. The mass was ill-defined, located in the upper outer quadrant area of her breast, and was 2 cm in diameter. MRI examination showed that the tumor had a spiculation and an irregular edge. There were no regional lymph nodes in her axilla and supra-subscapular. The diagnosis was Class IV by the fine needle aspiration biopsy cytology. We diagnosed the left breast cancer being in T2N0M0, Stage IIA, then we carried out Bt (Auchincloss method) and Sentinel lymph node biopsy (SLNB). There were metastatic cancer cells in the sentinel lymph node. So, we added level II lymph nodes dissection. The histological diagnosis was papillotubular carcinoma, f+, n+ (8/11). The endocrine receptor status of the tumor was ER+, PgR+ and the HER2/neu score was 0. There was paraffinoma in the non-cancer area. We dosed 6 cycles of FEC chemotherapy (CPA 800 mg, EPI 80 mg, 5-FU 750 mg/body x 1 cycle). We recognized no side effects of the chemotherapy for the patient.
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PMID:[A case of breast cancer detected by MRI mammography after Hollywood syndrome]. 1631 41

The development of an oral formulation of vinorelbine (Navelbine softgelatine capsules, Pierre Fabre Pharma, Freiburg i.Br., Germany) represents a significant advance in the treatment of patients with cancer. Oral chemotherapy is more convenient for the patients and brings significant time savings. Vinorelbine is rapidly absorbed after oral ingestion. The bioavailability is in the range of 33 to 43% and is not affected by concomitant food intake or by vomiting occuring 1.5 h or later after dosing. No significant differences in the pharmacokinetics of oral vinorelbine were observed between elderly (> or =70 years) and younger patients. The recommended dose schedule for oral vinorelbine is 60 mg/m(2) weekly for the initial 3 weeks (cycle 1) and 80 mg/m(2) weekly thereafter. However, if severe neutropenia is encountered during the first cycle, treatment is continued with weekly doses of 60 mg/m(2). Bioavailability studies have demonstrated that oral vinorelbine doses of 60 and 80 mg/m(2) are comparable to intravenous doses of 25 and 30 mg/m(2), respectively. Several clinical studies have demonstrated that the new oral formulation of vinorelbine can be safely administered, even to elderly patients, and is comparable in activity to intravenous vinorelbine in advanced non-small cell lung cancer (NSCLC) and metastatic breast cancer (MBC). A randomized phase II comparison of oral vinorelbine at the recommended dose schedule vs. intravenous vinorelbine at 30 mg/(2) in patients with advanced NSCLC found no significant differences in response rate, progression-free and overall survival between the two treatments. In studies of combination chemotherapy using vinorelbine plus cisplatin or carboplatin in advanced NSCLC, or vinorelbine plus taxanes, capecitabine,epirubicin, or the monoclonal HER2/neu antibody trastuzumab in MBC, intravenous vinorelbine could be completely or partially replaced by oral vinorelbine, resulting in maintained efficacy, good tolerability and improved patient convenience. Concurrent chemoradiation with oral vinorelbine and cisplatin was shown to be well tolerated and produced significant down-staging in patients with locally advanced NSCLC. Metronomic chemotherapy is a new treatment approach designed to maximize the antiangiogenic effect. Oral vinorelbine given every other day at low doses is currently evaluated in patients with refractory solid tumors. Oral vinorelbine has also proven useful as a substitute for intravenous vinorelbine in patients experiencing intractable acute tumor pain during or after intravenous infusion of vinorelbine.
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PMID:[Oral vinorelbine: pharmacology and treatment outcome in non-small cell bronchial carcinoma and breast carcinoma]. 1653 41

Two women, aged 57 and 55 years, with metastatic breast cancer were admitted for uncontrolled pain due to bone metastases. Despite the fact that progressive disease was evident, a change in antitumour therapy had not been recommended. The pain control was optimised in both patients. In one patient, palliative chemotherapy was installed, combined with trastuzumab because of HER2/neu overexpression. She was still alive after one and a half year of treatment. The other patient could not adjust mentally to the fact that her palliative therapy was changed to antitumour therapy; she died one month later. It is important to be aware of the various kinds of therapy in metastatic breast cancer because palliative treatment is more than just symptomatic treatment. Systemic antitumour therapy includes hormone therapy, chemotherapy and targeted therapy. Furthermore, in patients with bone metastases, radiotherapy combined with bisphosphonates results in pain relief and can reduce skeletal complications. Because of the ensuing complexity of the treatment of metastatic breast cancer, these patients should be regularly managed by a breast-cancer care team in order to improve the quality of care.
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PMID:[Palliation in patients with metastatic breast cancer often better with antitumour treatment than with only symptomatic treatment]. 1744 91

We investigated efficacy of gefitinib in hormone-refractory prostate cancer. Between March 2003 and December 2004, 23 patients with hormone-refractory prostate cancer were assigned to receive 250 mg oral gefitinib daily in addition to antiandrogen and luteinizing hormone-releasing hormone analogue for at least 2 months or until disease progression. Patients with progression stopped antiandrogen therapy, and received gefitinib and the luteinizing hormone-releasing hormone analogue. Serum HER2 and epidermal growth factor receptor extracellular domain were evaluated every 2 months. Gefitinib treatment did not result in any objective measurable response or responses in prostate-specific antigen. Median time to progression was 70 days (33-336). Median overall survival was 293 days (25-75 percentile: 235-349). HER2 extracellular domain mean value was 9.6 ng/ml (range 6.9-13.3) at basal time and was 10.1 (range 6.0-14.1) after 2 months. Epidermal growth factor receptor mean basal value was 51.0 ng/ml (range 41.4-75.3). After 2 months of treatment the mean value was 51.1 ng/ml (range 41.5-61.4). One patient had reduction in the pain score from baseline without an increase in the analgesic score. Four patients (17%) out of 23 had pain progression with an increase from baseline of at least 25% in the analgesic score. The study was discontinued before target accrual was reached owing to lack of efficacy of the drug. Our results do not support the efficacy of gefitinib in combination with endocrine treatment for hormone-refractory prostate cancer.
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PMID:Gefitinib combined with endocrine manipulation in patients with hormone-refractory prostate cancer: quality of life and surrogate markers of activity. 1766 1

This study aimed to evaluate the role of the knee joint in the neurosensory organization of balance control and the generation of postural sensorimotor strategies. Ten patients, aged over 60 years and having undergone unilateral total knee replacement (TKR) for osteoarthritis, and 20 controls were submitted to static and dynamic posturographic tests and to a sensory organization test (SOT) aiming at evaluating postural control in quiet stance and during movement. The patients were submitted to these evaluations after the disappearance of pain (TKR(1)) and at the end of a 6-week rehabilitation program (TKR(2)). Balance control being greatly improved at TKR2 compared to TKR1, the patients attain a quality of postural regulation similar to that of the controls; some postural abnormalities did however persist for the static test. Moreover, SOT values at TKR(2) close to those of the controls highlighted an improvement in motor response, better management in altered proprioceptive information situations, and greater use of the ankle to control balance. This model of intervention on the knee joint, namely knee replacement due to osteoarthritis, has shown that gradual functional sensorimotor restoration after TKR, due to intrasensory proprioceptive compensation either at knee, or at other joint levels (hip/ankle), improves dynamic balance control. This reacquisition allows the knee joint to recover its corrective compensatory role in postural regulation allowing, through neuroplasticity, the modification of muscular activation sequences and, thus, the implementation of anticipatory sensorimotor strategies.
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PMID:On the role of knee joint in balance control and postural strategies: effects of total knee replacement in elderly subjects with knee osteoarthritis. 2045 90


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