Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1981, the National Cancer Institute undertook Phase II trials of interferon alfa-2a in patients with non-Hodgkin's lymphoma (including cutaneous T-cell lymphoma [CTCL]) and chronic lymphocytic leukemia (CLL). A dose of 50 X 10(6) U/m2, three times per week, was used initially, then adjusted downward as dictated by toxic effects. A 54% response rate was achieved among 24 patients with low-grade non-Hodgkin's lymphomas, and the median duration of response was 8 months. Less encouraging results emerged from studies in patients with intermediate- or high-grade disease. Responses were noted in only two of six patients in the former group, and only one of seven in the latter group. Results have likewise been disappointing in patients with CLL. Of 18 individuals treated, only two exhibited brief, partial responses. In CTCL, on the other hand, alpha interferon may be the most effective single agent. Among 20 patients with advanced disease who had failed previous therapies, 45% responded. The primary dose-limiting toxicity in all these trials has been flu-like symptoms, particularly fever and fatigue. Fever has generally resolved as treatment has been continued, but dosage reductions are usually necessary to alleviate fatigue. Future studies are likely to focus on the use of alpha interferon in combination with chemotherapeutic agents or other biologic response modifiers, such as monoclonal antibodies.
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PMID:Interferon therapy of non-Hodgkin's lymphoma. 349 59

Romidepsin (depsipeptide or FK228) is a histone deacetylase inhibitor, one of a new class of agents active in T-cell lymphoma. A phase 2 trial was conducted in cutaneous (CTCL) and peripheral (PTCL) T-cell lymphoma. Major and durable responses in CTCL supported the approval of romidepsin for CTCL. Forty-seven patients with PTCL of various subtypes including PTCL NOS, angioimmunoblastic, ALK-negative anaplastic large cell lymphoma, and enteropathy-associated T-cell lymphoma were enrolled. All patients had received prior therapy with a median of 3 previous treatments (range 1-11); 18 (38%) had undergone stem-cell transplant. All patients were evaluated for toxicity; 2 patients discovered to be ineligible were excluded from response assessment. Common toxicities were nausea, fatigue, and transient thrombocytopenia and granulocytopenia. Complete responses were observed in 8 and partial responses in 9 of 45 patients, for an overall response rate of 38% (95% confidence interval 24%-53%). The median duration of overall response was 8.9 months (range 2-74). Responses were observed in various subtypes, with 6 responses among the 18 patients with prior stem-cell transplant. The histone deacetylase inhibitor romidepsin has single agent clinical activity associated with durable responses in patients with relapsed PTCL.
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PMID:Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. 2163 14