Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphocytopenia is a prognostic factor for shorter survival in advanced lung cancer and it is likely related to an interleukin-2 (IL-2) deficiency occurring during cancer progression. Major surgery itself for cancer is known to induce lymphocytopenia in the postoperative period. Postoperative lymphocyte decrease in colorectal cancer can be prevented by preoperative administration of recombinant human (rhIL-2), indicating that it is possible to drive appropriately important host defence agents during critical events, such as major surgery. The aim of this study is to verify if recombinant human interleukin-2 (rhIL-2) administered preoperatively is able to prevent the lymphocyte decrease occurring after radical surgery in operable lung cancer. This phase II study included 40 patients with operable NSCLC screened as stage II or IIIA, randomized to receive rhIL-2, 9000000 IU subcutaneously twice daily for 3 days before surgery (treated group, 20 patients) or not (control group, 20 patients). At baseline, there were no significant differences in total lymphocyte number and lymphocyte subsets (T-cell, T-helper, CD8+, natural killer, CD4/CD8 ratio) between groups. Postoperatively the control group showed a decrease in total lymphocyte count, T-lymphocyte count, T-helper cell number and CD4/CD8 ratio, significant at the 14th postoperative day relative to baseline values. In contrast, in the rhIL-2 treated group, at the 3rd and at the 14th postoperative days, a significant increase was observed over both baseline and control group values of total lymphocyte count, T-cells and T-helper cells. NK cell number increased significantly only over the control group. CD4/CD8 ratio was increased at the 14th postoperative day significantly over both baseline and control values. At pathological staging after surgery, four patients in the rhIL-2 group and four in the control group resulted in stage pIIIB; one patient in the rhIL-2 group resulted in stage IV (contralateral metastasis). Indeed, 15/20 rhIL-2 treated patients and 16/20 control patients were radically operated. After a 24-month follow-up, 12/20 rhIL-2 treated patients were alive and 8/15 radically operated were disease-free; 8/20 control patients were alive and 4/16 radically operated were disease-free. Toxicity was mild to moderate and easy manageable; treatment was suspended in one patient due to skin rash with hypotension grade II. The preoperative administration of rhIL-2 is feasible and prevents lymphocyte decrease occurring postoperatively after surgery for lung cancer. Further studies are required to assess the impact on survival.
Lung Cancer 1998 Jun
PMID:Phase-II randomized study of pre-operative IL-2 administration in operable NSCLC. 973 54

The anthracenedione analogue, BBR 2778 is an active antitumour agent preclinically and has reduced potential for cardiotoxicity compared with other similar drugs in preclinical models. BBR 2778 was administered 3 weekly by a 1 h intravenous (i.v.) infusion to 24 patients and the dose escalated rapidly from 20 to 240 mg/m2. The dose-limiting toxicity (DLT) was neutropenia, common toxicity criteria (CTC) grade 4 in 3/5 patients at 240 mg/m2. Other toxicities > or = CTC grade 3 were: vomiting, lymphopenia, thrombocytopenia and lethargy. Blue discoloration of veins and urine was also noted. In 1 patient (120 mg/m2, four cycles) left ventricular ejection reaction (LVEF) fell (CTC grade 2) but with no clinical sequelae. BBR 2778 plasma pharmacokinetics were biphasic (mean t(1/2) at 180 mg/m2 = 14.1 h) and the urinary elimination of the unchanged drug was < 10%. In a patient with previously treated small cell lung carcinoma (SCLC), a 49% reduction in measurable disease was noted with resolution of pericardial and pleural effusions (120 mg/m2 x eight cycles). From the results of this phase I study a dose of 180 mg/m2 as a 1 h infusion every 3 weeks would be recommended for phase II trials.
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PMID:A clinical phase I and pharmacokinetic study of BBR 2778, a novel anthracenedione analogue, administered intravenously, 3 weekly. 1109 9

BBR 2778 is a novel aza-anthracenedione with no cardiotoxicity in preclinical models. This Phase I dose escalation trial of BBR 2778 was conducted to determine the maximum tolerated dose, the dose-limiting toxicity, and the pharmacokinetic profile of BBR 2778 in patients with advanced solid tumors. BBR 2778 was given in three consecutive weekly 30-min i.v. infusions over a 4-week cycle (cy). Thirty patients (pts) were treated with BBR 2778 at doses ranging from 5 to 150 mg/m2/week. The dose levels 5, 10, 16.5, 25, 37.5, 75, 112.5, and 150 mg/m2/week were investigated in 4 pts (9 cy), 3 pts (3 cy), 3 pts (5 cy), 6 pts (9 cy), 1 pt (1 cy), 4 pts (9 cy), 6 pts (18 cy), and 3 pts (4 cy), respectively. The dose-limiting toxicity was neutropenia, typically occurring at day 14. Other toxicities were mild to moderate and were principally thrombocytopenia, lymphopenia, alopecia, nausea, and vomiting and blue coloration of the skin and urine. No significant cardiac toxicity was observed. The plasma dose concentration curve fitted a biexponential profile, with a rapid distribution phase followed by a prolonged elimination phase (mean t1/2,z, 12 h). BBR 2778 displayed a large volume of distribution (range, 9.7-29.7 l/kg) with a high plasma clearance rate (0.75-1.31 l/h/kg). Less than 10% of the dose was recovered in urine as unchanged drug. The maximum tolerated dose was 150 mg/m2/week for 3 weeks, every 4 weeks. On the basis of this study, the recommended dose for Phase II studies is 112.5 mg/m2/week days 1 and 8 with individual optional administration at day 15, every 4 weeks. Antitumor activity was observed in patients with breast, small cell lung carcinoma, and facial cylindroma. This trial showed that BBR 2778 has a manageable toxicity profile on a weekly schedule. This lead compound of the aza-anthracenedione family shows promising antitumor activity and deserves Phase II investigation in patients with high risk of cumulative cardiotoxicity, such as anthracycline-pretreated breast cancer patients.
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PMID:A phase I and pharmacokinetic study of the novel aza-anthracenedione compound BBR 2778 in patients with advanced solid malignancies. 1120 16

We report on a case of cytomegalovirus (CMV) enterocolitis occurring in a 65-year-old patient after a first course of standard chemotherapy for a small cell lung carcinoma (SCLC). Colonic biopsies showed typical inclusion bodies, CMV IgM and IgG antibodies were found in the serum, and polymerase chain reaction for CMV-DNA was positive. Lymphopenia and diminished CD4 T-cell counts were observed. Diarrhoea ceased under ganciclovir treatment, the patient recovered, but died several months later of metastatic lung cancer. Significant immunosuppression leading to severe colitis by CMV infection or reactivation can occur after standard chemotherapy.
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PMID:Cytomegalovirus colitis--a severe complication after standard chemotherapy. 1465 Dec 17

Active specific immunotherapy with liposomal vaccines targeted to the mucinous carcinoma-associated glycoprotein MUC1 have shown promising results in animal models. The aim of this phase I study was to evaluate the safety and immunogenicity of 2 dose levels of the MUC1 liposomal vaccine preparation BLP25. Patients with stage IIIB or IV non-small-cell lung cancer received either 20 microg or 200 microg of the liposomal BLP25 vaccine preparation. Injections were administered subcutaneously at weeks 0, 2, 5, and 9. Immunological responses to vaccination were measured by antibody production, cytotoxic T lymphocytes (CTL), and proliferative T-helper cells. Seventeen patients were entered on study; 12 patients completed the vaccination protocol. Two patients, 1 in each dose group, developed clinically insignificant grade 3 lymphopenia during the study. Nonhematologic toxicities were mild and self-limiting, and there were no significant long-term injection site reactions. Immunological assays revealed the generation of CTLs against MUC1-positive tumor cell lines in 5 of 12 evaluable patients. These patients did not have CTLs prior to receiving the vaccine. No significant humoral response to the vaccination was observed. No objective antitumor responses were observed. Of the 12 patients completing all the vaccinations, 4 had stable disease. Median survival time was 5.4 months in the 20 microg group and 14.6 months in the 200 microg group. In summary, the BLP25 liposomal vaccine was well tolerated and elicited a primarily cellular immune response in these lung cancer patients. This study forms the basis for further clinical exploration of the MUC1 liposomal vaccine, BLP25.
Clin Lung Cancer 2001 Aug
PMID:Phase I study of the BLP25 (MUC1 peptide) liposomal vaccine for active specific immunotherapy in stage IIIB/IV non-small-cell lung cancer. 1465 92

This Phase I/II study investigated weekly docetaxel (Taxotere) with concurrent radiotherapy in 42 patients with untreated stage III non-small cell lung cancer (NSCLC). All patients were treated with chest irradiation: 2Gy administered 5 days/week for 5 weeks, to a total of 50Gy. Docetaxel (1-h infusion) was administered on days 1, 8, 22, and 29< or =2 h before radiation fractions 1, 6, 16, and 21 (i.e. every week excluding the third week of treatment). In the Phase I study (n=12), docetaxel was started at 20 mg/m2 per week (n=3) and escalated in 10 mg/m2 increments (30 mg/m2, n=3; 40 mg/m2, n=6). Dose-limiting toxicity (grade 3-4 esophagitis) occurred with docetaxel 40 mg/m2. The Phase II study (n=30), therefore, evaluated docetaxel 30 mg/m2 (considered recommended dose). All patients except one experienced asymptomatic grade 3-4 lymphopenia; four patients (9.5%) had grade 3-4 esophagitis. The overall response rate was 45.5%, with eight (24.2%) complete responses. The median time to progression at the recommended dose of 30 mg/m2 (n=33) was 12.0 months and the median survival time was 13.6 months. The 1-year survival rate was 60.6%. Five patients (one from Phase I and four from Phase II) were alive after >5 years. In conclusion, weekly docetaxel 30 mg/m2 plus radiotherapy is active and well tolerated in stage III NSCLC.
Lung Cancer 2005 Oct
PMID:Weekly docetaxel with concurrent radiotherapy in locally advanced non-small cell lung cancer: a phase I/II study with 5 years' follow-up. 1600 5

Strongyloidiasis can present with a wide variety of symptoms and can lead to a potentially fatal hyperinfection. Although any factors that suppress the host defense mechanisms can potentially trigger hyperinfection, prolonged steroid use has been quite well described. A patient with disseminated small cell lung cancer suffered a Strongyloides stercoralis hyperinfection syndrome complicating ectopic adrenocorticotropic hormone (Cushing syndrome). Evaluation revealed lymphopenia, elevated levels of adrenocorticotropic hormone in the setting of elevated cortisol levels, a normal pituitary, and metastatic malignancy. S. stercoralis larval forms were seen in the stool and sputum. At autopsy, S. stercoralis larval forms were seen in the lung along with evidence of metastatic small cell lung carcinoma.
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PMID:Strongyloides hyperinfection syndrome complicating (ectopic) Cushing syndrome. 1858 Jul 21

TLR-9 agonists are immunostimulating agents that have antitumor effects in animal models. A phase I trial was conducted to define the safety profile of subcutaneous injections, combined with intrathecally administration of CpG-28, a TRL 9 agonist, in patients with neoplastic meningitis (NM). Cohorts of 3-6 patients with NM were treated for 5 weeks with escalating doses of CpG-28. The primary endpoint was tolerance. Secondary endpoints were progression free survival (PFS) and overall survival (OS). Twenty-nine patients were treated with CpG-28. The primary cancers were malignant glioma, lung carcinoma, breast cancer, melanoma or melanocytoma, ependymoma, and colorectal cancer. The median age was 56 years and median Karnovsky Performance status (KPS) was 70%. The treatment was well tolerated. Adverse effects that were possibly or probably related to the studied drug were grade 2 lymphopenia, anemia and neutropenia, local erythema at injection sites, fever and seizure. There were five serious adverse events: two confusions, two infections of ventricular devices and one grade 4 thrombopenia and neutropenia. The median PFS was 7 weeks and median OS was 15 weeks. Interestingly, the median survival was slightly (but not significantly) higher in the eight patients who were concomitantly treated with bevacizumab (19 weeks vs 15 weeks; P = 0.11). CpG-28 was well tolerated at doses up to 0.3 mg/kg subcutaneously and 18 mg intrathecally. Additional trials are warranted.
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PMID:Immunotherapy with CpG-ODN in neoplastic meningitis: A phase I trial. 2609 10