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)

To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m(-2) q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed >6 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9-43.2%)). Among the responders, seven patients had relapsed during a period of <3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2-7.2), median progression-free survival was 3.7 months (95% CI: 2.8-4.2) and median overall survival was 14.3 months (95% CI: 9.2-19.6). The most frequent adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of patients) and constipation (grade 3 in 11.7% of patients) were also common; these were non-cumulative and manageable permitting achievement of a good relative dose intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in the management of MBC patients previously treated with (A/T)-based regimens. These encouraging phase II results warrant further investigation of this novel agent in combination with other active agents in this setting or in earlier stages of disease.
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PMID:Vinflunine: a new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy. 1703 8

On September 27, 2006, the U.S. Food and Drug Administration granted approval to panitumumab (Vectibix, Amgen, Inc., Thousand Oaks, CA) for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Panitumumab approval is based on the results of a single, open-label, randomized, multinational study that enrolled 463 patients with EGFR-expressing (at least 1+ membrane staining in > or =1% of tumor cells) metastatic colorectal cancer. Patients were randomized to either best supportive care (BSC) alone or BSC plus panitumumab, 6 mg/kg i.v., every other week. The primary study endpoint was progression-free survival (PFS), determined by an independent review committee that was blinded as to treatment assignment. BSC patients who progressed were eligible to receive panitumumab. The study patients' median age was 62 years, with 40% aged > or =65; 63% were male, 99% were white, 86% had a baseline Eastern Cooperative Oncology Group performance status score of 0 or 1, and 67% had colon cancer. The median time from diagnosis of metastases was approximately 19 months and the median number of prior therapies was 2.4. The PFS duration was significantly longer among patients randomized to receive panitumumab in addition to BSC (n = 231) compared with BSC alone (n = 232). The median and mean PFS times were 56 and 96.4 days, respectively, for patients receiving panitumumab and 51 and 59.7 days, respectively, for patients receiving BSC alone. Nineteen partial responses (8%, 95% confidence interval [CI], 5.3%-12.5%) were observed in panitumumab treated patients. The median duration of response was 17 weeks (95% CI, 16-25 weeks). Approximately 75% of patients in the BSC alone arm crossed over to receive panitumumab after disease progression. There was no difference in overall survival between the two study arms. The most common adverse events were skin rash, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea. The most serious adverse events were pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, diarrhea, and constipation.
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PMID:FDA drug approval summary: panitumumab (Vectibix). 1752 46

Carcinoma of the colon and rectum are rare in children and under the age of 40 years. A case of coro-rectal carcinoma in a nine-year-old Nigerian male child is reported. Family history was significant in the patient, it revealed that his father died three years earlier because of chronic diarrhoea and mucoid stool with associated on and off constipation and one of his elder brothers died eight years ago of colonic cancer at the age of twenty years. Exploratory laparotomy was done for the patient which revealed fixed rectosigmoid tumour with metastases to the liver, omentum and small intestine and ascites was also found. Hartmann's procedure with sigmoid colostomy was performed and the tumour was resected. Histological report of the biopsy specimen was consistent with poorly differentiated adeno-carcinoma. To the best of our knowledge, the youngest patient recorded in the literature is seven years old, which is younger than our patient, but this is still the youngest in our records.
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PMID:Rectal carcinoma in a nine-year-old Nigerian male child: case report. 1759 71

We report the rare case of a 74-year-old man who was admitted to our hospital with rapid progression of tetraparesis, which was most apparent in the lower right limb, sensory disturbances from C3 to S1 on the left side and recent onset of constipation and urinary retention. There was no known history of cancer. As MRI of the neck disclosed a cervical intramedullary mass lesion at C 4/5 level suspicious for a primary glial tumour, the patient underwent surgery. After microsurgical excision the histological analysis of the lesion unexpectedly revealed an intramedullary spinal cord metastasis (ISCM) of a poorly differentiated carcinoma, immunohistochemically consistent with a bronchial carcinoma. As intramedullary spinal cord metastases are generally associated with poor survival, a palliative irradiation of the levels C1-6 was additionally performed. Unfortunately tetraparesis and numbness remained. The very rare occurrence of intramedullary spinal cord metastasis and the absence of pathognomonic symptoms often lead to a delay until an underlying malignancy is discovered. Although rare, intramedullary spinal cord metastasis should be considered as a differential diagnosis of a spinal intramedullary lesion. Surgery and radiation are both options in the controversially discussed treatment of ISCM.
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PMID:Intramedullary spinal cord metastasis as initial presentation of systemic cancer--report of a rare case. 1796 82

Temozolomide is an oral alkylating agent used in the treatment of metastatic melanoma. Commonly reported adverse effects of the drug include nausea and vomiting, constipation, headache, and fatigue, as well as myelosuppression, which may be dose limiting. Few reports have described dermatologic adverse effects such as rash and pruritus, and, to our knowledge, none have discussed the seriousness or extensiveness of the rash. We describe a 37-year-old woman who was receiving temozolomide for treatment of metastatic melanoma. After 6 weeks of therapy, the patient developed an unexplained fever. The drug was discontinued, and the fever resolved within 2 days. Temozolomide was restarted 2 months later; the patient again developed a fever. This time the fever was accompanied by a diffuse erythematous skin rash that progressed to an extensive, full-body, desquamative skin rash. The rash was treated with moisturizing cream along with intravenous and topical corticosteroids and antibiotics. Due to the severity of the rash, temozolomide was permanently discontinued. Even after its discontinuation, the patient experienced the rash on a long-term basis, with periodic exacerbations. However, none were as severe as the first rash. The patient's metastatic disease remained stable for the next 2 years. According to the Naranjo adverse drug reaction probability scale, the likelihood that temozolomide was responsible for the adverse drug reaction of fever was probable (score of 6). Clinicians should be aware that an erythematous and exfoliative rash may be induced by temozolomide, and be familiar with the pharmacologic and supportive measures necessary for its treatment.
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PMID:Temozolomide-induced desquamative skin rash in a patient with metastatic melanoma. 1829 21

The World Health Organization recommends a step-by-step approach to the management of chronic cancer pain, called the analgesic ladder. Traditionally, morphine has been the prototypical opioid for chronic cancer pain because there is no ceiling effect or upper limit and it is a naturally occurring pure mu-opioid agonist. Occasionally, there are dose-limiting side effects and/or lack of efficacy. Opioid rotation is important because it improves analgesia and the side effect profile. Two principal reasons for failure of strong opioids are the presence of incident pain and/or neuropathic pain. Incident pain usually occurs in a patient with osseous metastases or another movement-related pain syndrome. Other reasons to rotate opioids are side effects such as intractable nausea and vomiting, sedation, dysphoria, delirium, and constipation, which are unresponsive to simple measures such as retitration, antiemetic agents, antipsychotic agents, psychostimulants, and laxatives. There are recent data that demonstrate that the accumulation of active metabolites in patients receiving common opioids such as morphine and hydromorphone are partly responsible for adverse effects. This premise has prompted clinicians and researchers to consider opioid rotation as a valid tool for cancer pain management to increase the probability of acceptable adverse effects with adequate analgesia. Methadone is an opioid agonist with a lack of known active metabolites, which are known to produce side effects with other opioids. Methadone has excellent bioavailability, making it a desirable analgesic agent for refractory types of cancer pain.
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PMID:The role of methadone in the treatment of moderate to severe cancer pain. 1862 69

The treacherous and deceptive nature of pheochromocytoma makes it crucial to detect and treat it promptly; otherwise it will almost certainly be fatal from cardiovascular complications or metastases. Hypertension occurring in patients with pheochromocytomas is sustained in about 50% and paroxysmal in the remainder; however, many patients remain normotensive. Hypertension attacks may be precipitated by physical activity, postural changes, anxiety, certain foods or wine, some drugs, operative procedures, etc. Cardinal manifestations are paroxysmal hypertension, headache, palpitations +/- tachycardia, inappropriate sweating; anxiety, tremulousness, pallor (rarely flushing), chest and abdominal pains; nausea and vomiting often occur. Hypercatecholaminemia manifestations are more common and pronounced when paroxysmal hypertension occurs, but persons with familial pheochromocytoma may be asymptomatic. Protean manifestations of pheochromocytoma may simulate many conditions, some of which may have elevated plasma and urine catecholamines and their metabolites. Baro-reflex failure, postural tachycardia syndrome, sleep apnea, carcinoid, renal failure, and pseudopheochromocytoma may be diagnostic challenges. The history, physical examination, biochemical testing (after eliminating interfering drugs, when possible) for plasma and urinary metanephrines can usually establish or exclude presence of pheochromocytomas. Occasionally a clonidine suppression test is needed to differentiate neurogenic from pheochromocytic hypertension. Manifestations suggesting hypercatecholaminemia without hypertension are highly atypical of pheochromocytoma. Pheochromocytoma may present as panic attacks, pre-eclampsia, cardiomyopathy, infection with fever and leucocytosis, diabetes, migraine, shock, Cushing's syndrome, multiple organ failure with lactic acidosis, neurological manifestations, transitory electrocardiogram abnormalities, constipation, intestinal obstruction, visual impairment, convulsions, etc. The key to diagnosis is always to think of pheochromocytoma in the differential diagnosis of hypertension.
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PMID:The protean manifestations of pheochromocytoma. 1924 99

We report on five patients (three males and two females), with a median age of 66.2 years (range, 58-73 years) who were admitted in our department from April 1998 until January 2004 with the diagnosis of rectal gastrointestinal stromal tumor (GIST). Their main symptoms were rectal bleeding, constipation and abdominal discomfort. Two patients were treated by an abdominoperineal resection of the rectum. One patient received palliative surgical treatment and adjuvant therapy with imatinib for metastatic disease. Another patient presented with complete rectal prolapse, and was treated with Delorme's procedure. The subsequent pathological examination of the resected specimen showed positive resection margins and was given adjuvant therapy with imatinib. Finally, one case was considered inoperable. However, after nine months of treatment with imatinib, the magnetic resonance imaging (MRI) scan revealed a significant reduction in the tumor size, and the patient was treated with abdominoperineal excision of the rectum. All cases have been proved to be immunohistochemically positive for the CD117 and the CD34 stain. During the follow-up period (mean duration 3.7 years), one patient died of progressive disease while the other four had no sign of recurrence.
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PMID:Gastrointestinal stromal tumors of the rectum: report of five cases. 1963 85

We report the case of a patient with metastatic hormone refractory prostate cancer in whom "indirect" cauda equina syndrome developed concurrent with multilevel spinal cord compression (SCC). Three months after his first positive bone scan, a 65-year-old otherwise healthy man presented with severe back pain, bilateral lower extremity paresthesias, leg weakness and urinary retention. Magnetic resonance imaging (MRI) showed a dural-based mass causing SCC at the T9, T10 and T11 vertebrae, with a normal cauda equina. He received corticosteroids and palliative external beam radiotherapy, resulting in good pain control and gradual improvement in his neurological symptoms. He did well for 8 months, at which time his residual bilateral leg weakness abruptly worsened and he experienced numbness, paresthesias, urinary incontinence and constipation. Repeat MRI showed progression of epidural metastatic disease compressing the spinal cord or thecal sac at 7 thoracic vertebral levels. The cauda equina was also distorted and flattened without evidence of direct solid tumour impingement. We hypothesized that the etiology was increased intrathecal pressure due to disrupted cerebrospinal fluid flow resulting from multiple levels of upstream thecal sac compression. It is essential to image the entire spinal cord and cauda equina when patients with metastatic bone disease present with neurological symptoms to institute correct treatment and preserve function and mobility.
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PMID:A case of indirect cauda equina syndrome from metastatic prostate cancer. 1967 34

Small cell lung cancer (SCLC) has a very aggressive clinical progression with widespread metastases. We describe the case of a patient with SCLC treated with concurrent chemoradiotherapy. One month later, after finishing the scheduled treatment, the patient was admitted to the hospital again with symptoms of low back pain that radiated to bilateral lower legs with painful paresthesias, urinary incontinence, and constipation. After a series of examinations, including bone scan and magnetic resonance imaging, the patient received an L2-L3 laminectomy. The concluded diagnosis through histopathologic examination with immunohistochemistry was extramedullary-intradural spinal metastasis causing cauda equina syndrome. The metastatic tumour originated from the SCLC. To the best of our knowledge, this is the first reported case of SCLC metastasized to the cauda equina causing cauda equina syndrome.
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PMID:Extramedullary-intradural spinal metastasis of small cell lung cancer causing cauda equina syndrome. 2001 82


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