Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

119 patients with metastatic melanoma received fotemustine 100 mg/m2 on days 1 and 8 and dacarbazine 250 mg/m2 on days 15-18. After a 5-week rest, fotemustine 100 mg/m2 on day 1 and dacarbazine 250 mg/m2 on days 2-5 was given every 3-4 weeks. 12 complete responses (11.6%) and 16 partial responses were observed in 103 evaluable patients (response rate 27.2%). The median duration of response was 21.5+ weeks (8+ to 53+). The response rate was 26.3% in CNS, 18.2% in visceral sites and 37.5% in non-visceral sites. The toxicity was mainly haematological: grade III-IV leukopenia in 27.4% and thrombocytopenia in 23.4%. The response rate was lower than that in 63 patients previously reported. The present series had a higher median age (54 vs. 40 years) without any differences in other population variables. However, activity on CNS metastases and on non-visceral sites was confirmed. Haematological toxicity was about 50% lower than that with fotemustine alone. Hence, this is an active outpatient regimen for metastatic melanoma, especially against cerebral and non-visceral metastases.
 ...
PMID:Fotemustine plus dacarbazine for malignant melanoma. 138 14

Therapy of metastatic melanoma still remains difficult. All therapeutic strategies have to consider the individual patient's condition and number and localisation of the metastases. Solitary metastases in lung, CNS, soft tissues and lymph nodes have to be removed by surgery. Multiple metastases are treated with a systemic chemoimmunotherpy. Promising approaches use interleukin-2, interferons, DTIC, temozolamide, vindesine and cisplatin. Radiotherapy is the treatment of first choice for bone and CNS metastases. These therapeutic strategies have improved the prognosis of metastatic melanoma. Additional multi-center trials and experimental approaches will help to reach the goal of a curative systemic therapy for metastatic melanoma.
 ...
PMID:[Systemic therapy of metastatic melanoma]. 1042 Aug 16

Melanoma frequently metastasizes to the central nervous system (CNS). The diagnosis of CNS metastases typically is made following the onset of clinical symptoms. Thus, more sensitive diagnostic approaches are needed to identify subclinical CNS metastases. Currently, standard cytologic analysis of the cerebrospinal fluid (CSF) is limited by its poor sensitivity. A more sensitive assay was therefore developed using multiple reverse transcriptase-polymerase chain reaction (RT-PCR) markers. CSF was collected and assessed by RT-PCR for three known melanoma-associated markers (MAGE-3, MART-1, and tyrosinase) to detect occult metastatic melanoma cells in the CSF of 37 American Joint Committee on Cancer (AJCC) stage IV melanoma patients. Cytologic analysis of CSF was performed on all patients, and immunohistochemistry (IHC) analysis was performed on 33 CSF samples using anti-S100 and anti-HMB-45 antibodies. Only one patient (3%) had tumor-positive CSF cytology and IHC upon entry into the study, whereas 12 patients (32%) were positive for at least one RT-PCR marker. The correlation between CSF RT-PCR positivity of MART-1 and/or MAGE-3 and the development of CNS metastases at 3 mo was significant (p = 0.04). Fifteen of 37 patients (41%) had either positive MRI and/or positive RT-PCR results. Multimarker RT-PCR is more informative and sensitive than cytology/IHC in assessing the CSF of melanoma patients.
 ...
PMID:Molecular detection of metastatic melanoma cells in cerebrospinal fluid in melanoma patients. 1151 19

Metastasis to the CNS develops in nearly half of patients with advanced melanoma; in 15% to 20% of these patients, the CNS is the first site of relapse. While systemic therapy for metastatic melanoma produces objective responses in 15% to 50% of patients, the available drugs do not penetrate well into the CNS, and these patients rarely benefit from systemic therapy. Although brain metastasis may be treated with surgery and/or stereotactic radiosurgery (SRS) when disease is limited to approximately one to three lesions, treatment for patients with large or multiple metastases is limited to whole brain irradiation (WBRT). While formal response and survival analyses of the impact of WBRT in melanoma have not been reported, the estimated median survival time for unselected patients with CNS metastases is only 2 to 4 months, with 1-year survival rates of less than 13%. In a selected population of patients with limited CNS involvement, surgical resection alone or in combination with WBRT appears to prolong median survival. More recently, SRS has been shown to be an effective local treatment for selected patients with brain metastases. In several retrospective reports of patients with melanoma CNS metastases, treatment with surgical resection alone or in combination with WBRT has been demonstrated to prolong median survival. More recently, SRS has been shown to be an effective local treatment for selected patients with brain metastases. In several retrospective reports, patients with CNS metastases from melanoma treated with a combination of WBRT plus SRS or SRS alone had median survivals and rates of control in the CNS superior to published reports for traditional WBRT. Most of these patients died from progressive extracranial disease with locally controlled CNS disease. Investigation of the contribution of newer systemic agents to the control of melanoma metastatic to the CNS has been based on the identification of drugs that have antitumor activity and the ability to cross the blood-brain barrier. Fotemustine is a nitrosourea that produced similar activity in CNS metastasis as in systemic disease, with a response rate of about 25%. Temozolomide (TMZ) is an oral alkylating agent that acts via the same mechanism as dacarbazine (DTIC), the most active single agent in melanoma. TMZ, which is highly active in brain tumors, has also been associated with activity in systemic and CNS metastases in melanoma patients, also in the 25% range. Efforts are underway to assess the additive benefit of TMZ and other drugs to WBRT or focused radiotherapy in this disease.
 ...
PMID:The treatment of brain metastases from malignant melanoma. 1240 17

The management of metastatic melanoma in 2005 remains a major clinical challenge. Multidisciplinary treatment planning and careful attention to sites of metastases, tumor biology, and comorbid conditions are critical to making the best clinical decisions for individual patients. No standard of care exists because no systemic therapies have yet shown efficacy in phase III trials. Single-agent or combination chemotherapy has not impacted over-all survival, and response rates are of short duration. High-dose IL-2 produces durable responses in a small subset (7%) of highly selected patients and has considerable toxicity and quality-of-life trade-offs. Biochemotherapy results in overall higher responses, but its impact on overall survival has been disappointing and its toxicity and expense are considerable. Re-searchers are further investigating biochemotherapy modifications with maintenance biotherapy and CNS consolidation in effort to increase durability of responses and prevent or delay the devastating sequela of CNS metastases. Despite a disappointing past, the advancement of science and a better understanding of critical cellular targets and pathways make the future of melanoma research encouraging. Clinical trials are actively studying novel immune potentiators, cytotoxics, and targeted therapies. Combinations of these new agents will likely be necessary to advance the treatment of the dis-ease. All patients should be encouraged to participate in clinical trials.
 ...
PMID:Management of metastatic melanoma 2005. 1663 24

Optimal treatment of metastases to the central nervous system (CNS) in patients with malignant melanoma remains a clinical challenge. In particular, for patients with BRAF-mutant melanoma and CNS metastases, much remains unknown about the safety and efficacy of the novel BRAF-targeted agents when administered in close sequence with radiation. We report two cases of rapid development of CNS radiation necrosis in patients with metastatic melanoma treated with the BRAF inhibitor, vemurafenib, closely sequenced with stereotactic radiosurgery or fractionated stereotactic radiation therapy. In the absence of prospective safety data from clinical trials, we advise vigilance in monitoring patients with BRAF-mutant melanoma whose treatment plan includes CNS radiation and vemurafenib and caution when assessing treatment response within the CNS in these patients.
...
PMID:Radiation necrosis mimicking rapid intracranial progression of melanoma metastasis in two patients treated with vemurafenib. 2440 65

The discovery of the BRAFV600 mutation and the development of targeted therapies directed against this mutation as well as effective immunotherapies with durable benefits have revolutionized the treatment of patients with melanoma. Nonetheless, the frequent occurrence of brain metastases in patients with advanced melanoma represents a significant obstacle to long-term, high quality survival. The application of stereotactic radiation therapy has provided an opportunity to control brain metastases in the majority of patients with metastatic melanoma reducing the impact of these lesions on morbidity and mortality and enabling patients to receive and potentially benefit from these novel systemic treatments. Encouragingly, several of these novel new therapies have shown antitumor activity against CNS metastases that approach that seen against extracranial disease. As a consequence, several effective treatment options are now available for patients with melanoma brain metastases. With these tools in hand, it is anticipated that further investigation into the optimal sequence and/or combination of systemic therapies and local therapies along with multidisciplinary team practice will continue to improve the outcome of patients with this previously life-limiting disease complication.
...
PMID:Treatment of Melanoma CNS Metastases. 2660 67

OBJECTIVE Recent advancements in molecular biology have identified the BRAF mutation as a common mutation in melanoma. The wide use of BRAF kinase inhibitor ( BRAFi) in patients with metastatic melanoma has been established. The objective of this study was to examine the impact of BRAF mutation status and use of BRAFi in conjunction with stereotactic radiosurgery (SRS). METHODS This was a single-center retrospective study. Patient's charts and electronic records were reviewed for date of diagnosis of primary malignancy, BRAF mutation status, chemotherapies used, date of the diagnosis of CNS metastases, date of SRS, survival, local tumor control after SRS, and adverse events. Patients were divided into 3 groups: Group A, those with mutant BRAF without BRAFi treatment (13 patients); Group B, those with mutant BRAF with BRAFi treatment (17 patients); and Group C, those with wild-type BRAF (35 patients). Within a cohort of 65 patients with the known BRAF mutation status and treated with SRS between 2010 and 2014, 436 individual brain metastases (BMs) were identified. Kaplan-Meier methodology was then used to compare survival based on each binary parameter. RESULTS Median survival times after the diagnosis of melanoma BM and after SRS were favorable in patients with a BRAF mutation and treated with SRS in conjunction with BRAFi (Group B) compared with the patients with wild-type BRAF (Group C, 23 vs 8 months and 13 vs 5 months, respectively; p < 0.01, log-rank test). SRS provided a local tumor control rate of 89.4% in the entire cohort of patients. Furthermore, the local control rate was improved in the patients treated with SRS in conjunction with BRAFi (Group B) compared with patients with wild-type (Group C) or with BRAF mutation but no BRAFi (Group A) as an adjunct treatment for BMs. CONCLUSIONS BRAF mutation status appears to play an important role as a potent prognostic factor in patients harboring melanoma BM. BRAFi in conjunction with SRS may benefit this group of patients in terms of BM survival and SRS with an acceptable safety profile.
 ...
PMID:BRAF V600E mutation and BRAF kinase inhibitors in conjunction with stereotactic radiosurgery for intracranial melanoma metastases. 2720 49

Metastases to the central nervous system (CNS) are one of the most common and lethal complications of metastatic melanoma. Historically, melanoma patients with CNS metastases have had dismal outcomes and very limited treatment options. However, the development of more effective targeted, immune, and radiation therapies is now leading to promising new investigations and strategies. Optimizing the development and testing of such strategies will benefit from an improved understanding of the unique molecular features of these tumors and the influence of the brain microenvironment. Accounting for unique clinical features and challenges of CNS metastases will also be critical to making significant clinical impact in patients.
 ...
PMID:Melanoma Brain Metastases: Current Areas of Investigation and Future Directions. 2811 58

Recently, immune checkpoint inhibitors have revolutionized cancer care by enhancing anti-tumor immunity. However, by virtue of stimulating the immune system, they can lead to immune-related adverse events (irAEs). Neurologic irAEs are uncommon but are becoming increasingly recognized and can be quite serious or even fatal. Furthermore, central nervous system (CNS) manifestations may be difficult to distinguish from CNS metastases, posing management challenges. Here, we describe a patient who developed exacerbation of sarcoidosis leading to CNS involvement following dual checkpoint blockade with nivolumab and ipilimumab for metastatic melanoma and review the relevant literature.
 ...
PMID:Neurosarcoidosis following Immune Checkpoint Inhibition. 3018 34


1 2 Next >>