Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The National Cancer Institute of Canada Clinical Trials Group undertook a phase II study of 2'-deoxycoformycin in patients with metastatic renal cell carcinoma. When 2'-deoxycoformycin 4 mg/m2 was administered intravenously weekly for three weeks then every two weeks no significant antitumor activity was noted in 19 evaluable patients. Toxic effects experienced were as expected, consisting primarily of nausea/vomiting, anorexia, and lethargy. It is concluded that 2'-deoxycoformycin at this dose and schedule has no clinical activity in the treatment of metastatic renal cell carcinoma.
 ...
PMID:Phase II study of 2'-deoxycoformycin in patients with renal cell carcinoma. A National Cancer Institute of Canada Clinical Trials Group study. 178 28

Polyinosinic-polycytidylic acid, a double-stranded ribonucleic acid that is a potent inducer of interferon production, was used in a stabilized form to treat 11 patients with metastatic renal cell carcinoma. Seven patients completed a full course of 8 infusions at maximum tolerated dosage. All patients experienced transient fever and marked fatigue. Anorexia was mild. Transient leukopenia occurred in 3 patients and reversible elevation in creatinine was observed in 1. All 4 patients with brain metastases became lethargic, and 3 died during or shortly after therapy. Only 2 patients demonstrated measurable total regression of isolated metastases (pleural/pulmonary in 1 and bone in 1) but in both metastases at other sites progressed. No partial regressions were seen. Metastases at all other sites (liver, brain and renal fossa) progressed during therapy. Patients who appeared to respond and who performed best during therapy generally demonstrated a higher performance status initially. Expression of natural cytotoxicity in in vitro testing did not correlate with a demonstrated response to treatment.
 ...
PMID:Immunotherapy of metastatic renal cell carcinoma with polyinosinic-polycytidylic acid. 380 4

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m2 IV continuous infusion days 1-5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1-15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.
 ...
PMID:Phase II evaluation of merbarone in renal cell carcinoma. 786 Feb 33

Background: Patients with metastatic renal cell carcinoma (mRCC) are commonly treated with tyrosine kinase inhibitors (TKIs). An adverse effect frequently suffered by patients is lethargy, which often leads to dose reduction or drug cessation. We aimed to assess whether hypogonadism is related to treatment with TKIs. Methods: We prospectively assessed gonadal function in 41 consecutive males with mRCC treated with TKIs. Demographic, clinical, and biochemical variables were collected, and statistical analyses performed to assess correlation and survival. Data Capture for each patient was perfomred at the time of entry in the study. Results: There was a 77% incidence of hypogonadism in this cohort. Assessment of testosterone level and time on TKI treatment revealed a correlation with linear regression R2 of 0.24 and regression coefficient of -0.003 (p = 0.019). Odds ratio for hypogonadism at >30 months on TKIs was 12.1 (p = 0.011). Odds ratios above and below this value showed a confirmatory trend, suggesting that this may be a chronic adverse effect. Conclusions: Our findings provide an important and robust hypothesis for a prospective clinical trial to be performed. Expert Opinion: Given the present data, patients who have symptoms suggestive of hypogonadism must have an assessment of gonadal function and be treated.
 ...
PMID:Chronic tyrosine kinase inhibitor (TKI) use in metastatic renal cell carcinoma (mRCC): can this lead to the adverse effect of hypogonadism? 3099 30