Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0231528 (myalgia)
 6,565 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bryostatin 1 is a macrocyclic lactone derived from the marine invertebrate Bugula neritina. In vitro, bryostatin 1 activates protein kinase C (PKC), induces the differentiation of a number of cancer cell lineages, exhibits anti-tumour activity and augments the response of haemopoietic cells to certain growth factors. In vivo, bryostatin 1 is also immunomodulatory, but the range of tumours which respond to bryostatin 1 in xenograft tumour models is mostly the same as the in vitro tumour types, suggesting a direct mode of action. Nineteen patients with advanced malignancy were entered into a phase I study in which bryostatin 1 was given as a 24 h intravenous infusion, weekly, for 8 weeks. Myalgia was the dose-limiting toxicity and the maximum tolerated dose was 25 micrograms m-2 per week. The myalgia was cumulative and dose related, and chiefly affected the thighs, calves and muscles of extraocular movement. The mechanism of the myalgia is unknown. CTC grade 1 phlebitis affected every patient for at least one cycle and was caused by the diluent, PET, which contains polyethylene glycol, ethanol and Tween 80. Most patients experienced a 1 g dl-1 decrease in haemoglobin within 1 h of commencing the infusion which was associated with a decrease in haematocrit. Radiolabelled red cell studies were performed in one patient to investigate the anaemia. The survival of radiolabelled red cells during the week following treatment was the same as that seen in the week before treatment. However, there was a temporary accumulation of radiolabelled red cells in the liver during the first hour of treatment, suggesting that pooling of erythrocytes in the liver might account for the decrease in haematocrit. Total or activated PKC concentrations were measured in the peripheral blood mononuclear cells (PBMCs) of three patients for the first 4 h of treatment and during the last hour of the infusion. This showed that PKC activity was significantly modulated during the infusion. Bryostatin 1 is immunomodulatory in vitro, and we have confirmed this activity in vivo. An investigation of the first three cycles of treatment in seven patients showed an increased IL-2-induced proliferative response in peripheral blood lymphocytes and enhanced lymphokine-activated killer (LAK) activity. A previously reported rise in serum levels of interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF 1) was not confirmed in our study; of nine patients in this study, including patients at all dose levels, none showed an increase in these cytokines.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:A phase I trial of bryostatin 1 in patients with advanced malignancy using a 24 hour intravenous infusion. 764 Feb 33

The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m(2)) administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting > or = 6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.
 ...
PMID:Phase II study of biweekly plitidepsin as second-line therapy for advanced or metastatic transitional cell carcinoma of the urothelium. 1984 25

Regarding the frequency of muscular complains with the use of tyrosine kinase inhibitors (TKIs), we hypothesize that creatine kinase (CK) elevation may be more frequent than usually reported. We conducted a prospective study on patients treated with TKIs for solid tumors, to assess the incidence of CK increase on treatment. Most of the patients (105/155) had a gastrointestinal stromal tumor. Treatments were carried out with the following drugs: imatinib (87 cases); sunitinib (21 cases); HER antagonists (14 cases), other TKIs (15 cases); and imatinib-based combinations (2 cases). Myalgias were found in 50/155 patients (32%). Fifty-four patients (35%; 95%CI, 27-42%) had elevated CK. According to NCI-CTC grading, there was 49/54 (31%) grade 1 and 5/54 (3%) grade 2 (2.5 to 5 times ULN). CK elevation was more frequent with imatinib than with other TKIs (39 cases, 45% vs. 14 cases, 21%, respectively; chi-squared test: P=0.003), and CK was more likely to be abnormal in patients treated with any TKI for more than 6 months. We found increased CK in about one-third of patients under TKIs for solid tumors, including 3% of patients with CK as high as 2.5-5 times ULN.
 ...
PMID:Serum creatine kinase increase in patients treated with tyrosine kinase inhibitors for solid tumors. 2244 83