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)

Inoculation of syngeneic MRMT-1 mammary tumour cells into one tibia of female rats produced tumour growth within the bone associated with a reduction in bone mineral density (BMD) and bone mineral content (BMC), severe radiological signs of bone destruction, together with the development of behavioural mechanical allodynia and hyperalgesia. Histological and radiological examination showed that chronic treatment with the bisphosphonate, zoledronic acid (30 microg/kg, s.c.), for 19 days significantly inhibited tumour proliferation and preserved the cortical and trabecular bone structure. In addition, BMD and BMC were preserved and a dramatic reduction of tartrate resistant acid phosphatase-positive polykaryocytes (osteoclasts) was observed. In behavioural tests, chronic treatment with zoledronic acid but not the significantly less effective bisphosphonate, pamidronate, or the selective COX-2 inhibitor, celebrex, attenuated mechanical allodynia and hyperalgesia in the affected hind paw. Zoledronic acid also attenuated mechanical hyperalgesia associated with chronic peripheral neuropathy and inflammation in the rat. In contrast, pamidronate or clodronate did not have any anti-hyperalgesic effect on mechanical hyperalgesia in the neuropathic and inflammatory pain models. We conclude that zoledronic acid, in addition to, or independent from, its anti-metastatic and bone preserving therapeutic effects, is an anti-nociceptive agent in a rat model of metastatic cancer pain. This unique property of zoledronic acid amongst the bisphosphonate class of compounds could make this drug a preferred choice for the treatment of painful bone metastases in the clinic.
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PMID:Disease modifying and anti-nociceptive effects of the bisphosphonate, zoledronic acid in a model of bone cancer pain. 1246 93

We report a case in which lung adenocarcinoma with multiple pulmonary metastases was completely responsive to combination chemotherapy with carboplatin (CBDCA) and weekly paclitaxel (TXL). CBDCA AUC = 5 (day 1) and TXL 75 mg/m2 (day 1, 8, 15) were infused over 1 hour after short premedication on an outpatient basis. Administration was continued for 3 weeks followed by 1 week rest. The patient was a 54-year-old woman who suffered from lung adenocarcinoma with mediastinal lymph node metastases, stage III A, and underwent complete resection. However, multiple pulmonary metastases were found 3 years after operation. On an outpatient treatment, she was treated with CBDCA combined with weekly TXL for 6 cycles. The multiple pulmonary metastases had completely disappeared after 2 cycles and CEA decreased to within normal limit after 5 cycles. The toxic events were anemia (grade 2), leucocytopenia (grade 2) and alopecia (grade 3). No major adverse effects such as hypersensitivity reaction or peripheral neuropathy were observed.
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PMID:[Lung adenocarcinoma with multiple pulmonary metastases completely responsive to combination chemotherapy with carboplatin and weekly paclitaxel--a case report]. 1451 12

In-transit metastases for melanoma are a type of stage III regional metastatic disease that are intradermal or subcutaneous nodules growing within lymphatics and not in nodal basins. If the initial diagnosis is a limited number of in-transit metastases (1-3 nodules), the optimal management is simple surgical excision with minimal negative margins and primary closures and appropriate staging to look for any distant metastases. There is no role for wide excision of in-transit lesions as there is for primary melanoma because the entire extremity or that region of the body is at risk for recurrence. Patients who are diagnosed with additional lesions in a short period of time or patients who at initial diagnosis have large numbers of nodules are candidates for isolated limb perfusion (ILP). ILP is a regional administration of high-dose chemotherapeutics within an extremity using a cardiopulmonary bypass machine similar to cardiac surgery. Once isolation is obtained surgically, the limb is heated to what is considered mild hyperthermia (38.5 degrees -40 degrees C), then chemotherapeutics are administered at very high concentrations for a 60- to 90-minute treatment. The drug recirculates and, at the end of the treatment period, it is flushed from the extremity and the circulation is re-established. The optimal regimen is melphalan dosed per limb volume (10 mg/L limb volume for lower extremities and 13 mg/L limb volume for upper extremities) with mild hyperthermia for 60 minutes. Using this regimen, overall response rates between 80% and 90% and complete response rates between 55% and 65% can be obtained. The duration of response is typically 9 to 12 months and a subgroup of complete responders, which is 20% to 25% of the total patient population, typically have sustained complete responses. The major toxicities are skin erythema, myopathy, and peripheral neuropathy. There have been several studies adding high-dose tumor necrosis factor to ILP, but there is no clear benefit in the treatment of melanoma. Other new approaches include isolated limb infusion as a percutaneous procedure to avoid the surgical toxicity.
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PMID:Management of in-transit melanoma of the extremity with isolated limb perfusion. 1511 46

Paclitaxel (Taxol) and carboplatin are an effective combination regimen for treating advanced breast cancer. Gefitinib (IRESSA) is the first epidermal growth factor receptor tyrosine kinase inhibitor to be approved for cancer treatment. This multicenter phase II trial treated 68 patients with advanced breast cancer with paclitaxel (175 mg/m(2) over 3 h) and 3-weekly carboplatin (area under the curve of 6) for six cycles, and 250 mg/day gefitinib orally. Median age was 57 (range 35-77) years, patients had performance status 0 (69.1%), 1 (27.9%) 2 (2.9%), 82.4% of patients had visceral metastases and 63.2% had received adjuvant chemotherapy. Forty-eight (70.6%) patients completed six cycles of chemotherapy and 20 (29.4%) patients discontinued treatment (seven [10.3%] due to disease progression, seven [10.3%] due to toxicity, five [7.4%] withdrew consent and one [1.5%] died after the first cycle). Sixty-three (92.7%) patients were evaluable for response; nine (13.2%) had complete responses, 30 (44.1%) had partial responses, 21 (30.9%) had stable disease and three (4.4%) had disease progression. Grade 3/4 adverse events in > or =5% of patients except of alopecia, included neutropenia (17.7%), anemia (10.3%), diarrhea (7.4%), thrombocytopenia (5.9%) and peripheral neuropathy (5.9%). Of those tumor biopsies available for immunohistochemical analysis (n=60), 5.0% were positive and 35.0% negative for expression of all HER-family receptors. Comparable numbers of tumor biopsies were nuclear p27(kipl) positive and negative (39.7 and 42.7%, respectively), with the majority (72.1%) negative for cytoplasmic p27(kipl). The observed efficacy data in this study were similar to those reported for the combination of paclitaxel and carboplatin alone.
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PMID:Paclitaxel and carboplatin as first-line chemotherapy combined with gefitinib (IRESSA) in patients with advanced breast cancer: a phase I/II study conducted by the Hellenic Cooperative Oncology Group. 1598 Sep 85

A 48-year-old man underwent subtotal esophagectomy for pStage III (pT 3 pN 3) thoracic esophageal carcinoma on June 20, 2002, in combination with chemotherapy (5-FU 500 mg/day day 1-14, CDDP 10 mg/day day 1-14, VDS 3 mg on days 1 and 8) before and after the operation. Recurrence was seen 7 months after the operation in right pleura and lower mediastinum. Chemo (same regimen)-radiotherapy (50 Gy) was then performed but without effect. Thereafter, lung and upper mediastinal metastases were found, and weekly administration of paclitaxel (70 mg/m2, day 1, 8, 15, q 4w) was initiated in combination with radiotherapy (40 Gy). Two cycles of treatment resulted in PR, and CR was achieved after the 8th cycle was completed. Although treatment was terminated after the 12 th cycle due to development of peripheral neuropathy (grade 2), CR was still maintained 8 months after the completion of treatment. These results suggested the effectiveness of the treatment in cases that show resistance to conventional 5-FU-based chemotherapy.
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PMID:[A case of recurrent esophageal cancer successfully treated with weekly paclitaxel in combination with radiotherapy]. 1598 25

Chemotherapeutic combination regimens for advanced non-small cell lung cancer traditionally have been based on platin compounds. However, a mechanistic rationale could lead to effective non-platin combinations. Paclitaxel and vinorelbine are antimicrotubule agents with different mechanisms of action, both of which have single agent activity against non-small cell lung cancer. A Phase I/II trial of paclitaxel Day 1 and vinorelbine Days 1-3 every 21 days was, therefore, performed for patients with Stage IIIB or Stage IV non-small cell lung cancer who had not previously received chemotherapy for metastatic disease. In the Phase I investigation, up to 4 patients were treated at each dose level. The maximum tolerated dose level was found to be paclitaxel 150 mg/m2 IV Day 1 and vinorelbine 16 mg/m2 IV Days 1-3, with dose-limiting toxicities of fatigue, myalgia, and mucositis at higher doses. This dose level was then expanded with an additional 15 patients. Of the 23 patients treated for up to 10 cycles at or near the maximum tolerated dose level (19 patients with paclitaxel 150 mg/m2 IV Day 1 and vinorelbine 16 mg/m2 Days 1-3, and 4 patients with paclitaxel 150 mg/m2 IV Day 1 and vinorelbine 13 mg/m2 Days 1-3), 7 patients achieved partial response and 5 patients achieved minor response. Fatigue, myalgia, peripheral neuropathy, and transient leukopenia were the most common cumulative toxicities seen. The non-platin chemotherapy doublet of paclitaxel and vinorelbine given on this convenient 3-day schedule is worthy of further investigation in the treatment of non-small cell lung cancer.
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PMID:Phase I/II trial of paclitaxel and vinorelbine in advanced non-small cell lung cancer. 1619 46

This phase II trial was performed to evaluate the efficacy and tolerability of a new combination of Uracil/Ftorafur (UFT)/leucovorin (LV) and oxaliplatin in patients (pts) with metastatic colorectal cancer (MCRC) who had not received prior chemotherapy for metastatic disease. Between February 2002 and October 2002, 64 patients received UFT 300 mg m(-2) day(-1) and LV 90 mg day(-1) from day 1 to day 14 combined with oxaliplatin 130 mg m(-2) on day 1, every 3 weeks. All patients were evaluable for safety analysis and 58 of 64 patients were eligible for efficacy. Responses were reviewed by an independent review committee. Of the 58 per-protocol defined assessable patients, 1 complete response and 20 partial responses were observed yielding a response rate of 34% (95% CI: 22-47). The median response duration was 8.74 months (range 1.6-14). The median time to progression and the median survival were 5.88 months (95% CI: 4.34-8.21) and 18.2 months (95% CI: 10-20.7), respectively. Diarrhoea and peripheral neuropathy were the most frequent and predictable toxicities. These events were reversible, noncumulative and manageable. Grade 3 diarrhoea occurred in only 11% of the patients. No grade 4 gastrointestinal toxicity was reported in the study. The incidence of grade 3/4 (National Cancer Institute Common Toxicity Criteria 2: NCI-CTC 2) peripheral neuropathy was 15%. Haematological toxicity was of mild to moderate intensity with 10% of the patients with Grade 3/4 neutropenia without any episode of complication. The TEGAFOX regimen, a new combination using UFT/LV and oxaliplatin every 3 weeks is feasible on an outpatient basis. The combination is safe and active and may offer a promising alternative to the intravenous route. Nevertheless this efficacy results should be confirmed by randomized phase III trials.
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PMID:'A phase II study of oral uracil/ftorafur (UFT) plus leucovorin combined with oxaliplatin (TEGAFOX) as first-line treatment in patients with metastatic colorectal cancer'. 1640 62

Sarcoidosis is uncommon in children. Although isolated neurosarcoidosis has been seen in 15% adults with sarcoidosis, pediatric neurosarcoidosis is rarely reported. Neurosarcoidosis may present with cranial neuropathy, including facial palsy, optic nerve or other cranial nerve involvement, peripheral neuropathy, or manifestations of the central nervous system affecting the hypothalamus, pituitary gland, cerebral cortex, cerebellum, meninges, and spinal cord. The useful diagnostic investigations include magnetic resonance imaging of the brain and spinal cord, cerebrospinal fluid studies, brain and meningeal biopsy if feasible, chest radiography to reveal sarcoidosis, angiotensin-converting enzyme level in the serum or cerebrospinal fluid, and Kveim test when available. We herein report a case of isolated brain biopsy-confirmed neurosarcoidosis in a 17-year-old boy presenting with severe unilateral headache and multiple brain and spinal cord MRI lesions mimicking central nervous system metastases.
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PMID:Isolated neurosarcoidosis presenting as headache and multiple brain and spinal cord lesions mimicking central nervous system metastases. 1730 23

Genexol-PM is a novel Cremophor EL-free polymeric micelle formulation of paclitaxel. This single arm, multicenter phase II study was designed to evaluate the efficacy and safety of Genexol-PM in patients with histologically confirmed metastatic breast cancer (MBC). Forty-one women received Genexol-PM by intravenous infusion at 300 mg/m2 over 3 h every 3 weeks without premedication until disease progression or intolerability. A total of 331 chemotherapy cycles were administered, with a median of 8 cycles per patient (range, 1-16). Overall response rate was 58.5% (95% CI: 43.5-72.3) with 5 complete responses and 19 partial responses. Thirty-seven patients who received Genexol-PM as a first-line therapy for their metastatic disease showed a response rate of 59.5% (95% CI: 43.5-73.7), and two responses were reported in four patients treated in the second-line setting for their metastatic disease. The median time to progression (TTP) for all patients was 9.0 months (range, 1.0-17.0+ months). Grade 3 non-hematologic toxicities included sensory peripheral neuropathy (51.2%), and myalgia (2.4%). Eight patients (19.5%) experienced hypersensitivity reactions, with grade 3 in two patients. Hematologic toxicities were grade 3 and 4 neutropenia (51.2 and 17.1%, respectively), and grade 1 and 2 thrombocytopenia (22.0%). Notably, no febrile neutropenia was observed. Genexol-PM appears a promising new paclitaxel in view of significant efficacies. Further trials with different dosing schedules, durations of delivery, or in combination with other drugs are warranted.
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PMID:Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer. 1747 88

We report a case of recurrent gastric cancer with peritoneal dissemination and paraaortic lymph node metastases, successfully treated with weekly administration of paclitaxel. The patient was a 63-year-old man who underwent distal gastrectomy with lymph node dissection for advanced gastric cancer in February 2005. After the operation, adjuvant chemotherapy with S-1 was started and continued. He complained of abdominal distention, anorexia and nausea in April 2006. Therefore, paclitaxel (PTX) was administered at a dose of 60 mg/m(2)/day for 3 weeks followed by a week rest. Clinical symptoms were relieved, and abdominal X-ray findings showing intestinal obstruction disappeared after 2 courses. CT scan revealed metastatic lymph nodes were reduced after 3 courses. Grade 1 peripheral neuropathy and grade 2 leukocytopenia were noted, but no serious adverse reaction appeared. Weekly administration of PTX may be a promising regimen as second-line chemotherapy for S-1-resistant recurrent gastric cancer.
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PMID:[A case of S-1-resistant recurrent gastric cancer successfully treated with weekly administration of paclitaxel]. 1763 49


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