Doses Of Drugs In Combination Research Articles

Efficacy and safety of low-dose albumin-bound paclitaxel plus tislelizumab as second- or further lines treatment for elderly patients with metastatic non-small cell lung cancer.

e21066 Background: Lung cancer ranks first globally in morbidity and mortality rates among cancers. There are few studies focused on the different doses of chemotherapy drugs in combination with programmed cell death-1 (PD-1) inhibitors in non-small-cell lung cancer (NSCLC). Tislelizumab, a novel PD-1 monoclonal antibody, has been shown to improve antitumor activity when combined with chemotherapy as first-line treatment for patients with NSCLC. Elderly patients usually have poor physical conditions and many complications, resulted in higher risks of chemotherapy. This study aimed to preliminarily assess the efficacy and safety of low-dose chemotherapy plus tislelizumab for elderly patients with metastatic NSCLC. Methods: Eligible patients should be diagnosed as metastatic NSCLC, aged ≥65 years, and failed in one or more lines treatment. Patients with epidermal growth factor receptor (EGFR) / anaplastic lymphoma kinase (ALK) inhibitor resistance could be enrolled in the study. Participants received albumin-bound paclitaxel (130mg/m2) plus tislelizumab (200mg) every 3 weeks. Chemotherapy lasted for no more than 6 cycles. Once chemotherapy intolerance occurred or at end of 6 cycles, patients with objective response or stable disease would continue to receive tislelizumab until confirmed disease progression, death, and unacceptable toxicity. Primary endpoints were progression free survival (PFS) and safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), as well as overall survival (OS). Results: Total 23 patients were enrolled from May 2019 to March 2020: 43.5% (10/23) male, 39.1% (9/23) smokers, 26.1% (6/23) with squamous cell carcinoma and 56.5% (13/23) with ECOG 2. Median age was 71 yr (range: 65, 82). Patients had received 1 (47.8%) or ≥2 (52.2%) lines of therapy. 13 (56.5%) patients with EGFR/ALK TKI resistance participated in the study. As of data cut-off on December 1, 2020, the median PFS was 9.5 months (95% CI: 5.7–13.3 months). Nine patients achieved partial response (PR). The ORR was 39.1% (9/23) and DCR was 87.0% (20/23). Only 4 participants died in the study and the mOS was not reached. Sixteen (69.6%) patients had a decrease in tumor size as compared with baseline and the median change from baseline was −22%. 13 (56.5%) participants suffered at least one adverse event (grade 3 in 3 (13.0%) patients). The main adverse events were fatigue (17.4%), fever (17.4%), abnormal liver function (17.4%), rash (13.0%) and numbness (13.0%). No grade 4 adverse event was reported. Conclusions: Low-dose albumin-bound paclitaxel plus tislelizumab might be an optional choice for elderly patients with metastatic NSCLC after the failure of platinum-based chemotherapy or targeted therapy. Perspective clinical studies with large sample size are needed to validate our results.

Prolonged (more than ten hours) neuromuscular blockade after cardiac surgery: report of two cases

We examine two cases of prolonged neuromuscular blockade (NMB) after cardiac surgery. To the best of our knowledge, these are the first reported cases of complete paralysis lasting more than ten hours after surgery. We attribute the extended durations of NMB (more than ten hours) to high doses of NMB drugs in combination with magnesium sulphate and moderate renal failure. Advanced age, hepatic disease, aminoglycoside exposure, hypocalcemia, and possible interaction between rocuronium and pancuronium may have played minor roles. We should avoid administering large doses of NMB agents, even in the context of planned postoperative ventilation. If NMB is not monitored intraoperatively in patients who are at risk of prolonged NMB, then train-of-four response should be measured in the intensive care unit. Adequate sedation should be provided until proper recovery of neuromuscular function is documented.

COMPARATIVE STUDY OF COMBINED DRUGS OF ENALAPRIL MALEATE AND HYDROCHLOROTHIAZIDE: «RENIPRIL HT» AND «CO-RENITEC» IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

Aim. Tto study efficiency and safety of new combined drug of enalapril maleate and hydrochlorothiazide “Renipril HT: in patients with mild to moderate arterial hypertension (AH) in comparison with the original combined drug with the same substances – “Co-renitec”, possibility of reaching target blood pressure (BP) level with separate treatment with each drug, and in combination with atenolol if necessary. Material and methods. 30 patients (11 men and 19 women) with mild to moderate AH took part in randomized, open, cross over study. 10-14 days before the study started, previous antihypertensive treatment had been canceled for all the patients. Each patient by turns was treated during 6 weeks with Renipril HT (RH) and Co-renitec (CR). Efficiency of antihypertensive therapy was assessed at visits to physician every 2 weeks within the whole period of study. Within first 2 weeks patients were treated with RH 10/12,5 mg daily or CR 10/6,25 mg daily. Within next 2 weeks doses of drugs were doubled if target BP level (<140/90 mmHg) was not reached. If therapy with doubled doses of combined drugs was inefficient, atenolol 25 mg daily was added for the last 2 weeks of treatment with each drug. After 6-week treatment with the first randomized drug, antihypertensive therapy was canceled for 7-14 days depending on addition of atenolol to the therapy. Results. After 6-week treatment with RH average level of systolic BP reduced by 21,8 mmHg compared to the initial level, after 6-week treatment with CR – by 23,8 mmHg. Average level of diastolic BP reduced by 10,8 and 13,5 mmHg respectively (differences between drugs in BP decrease are not significant). By the end of 6-week treatment with RH target BP level was reached in 74% of patients, with CR - in 64% of patients. Bigger number of side-effects was registered in treatment with RH (p=0,03), but most part of them were not severe and didn’t demand therapy correction. Conclusion. New combined drug of enalapril maleate and hydrochlorothiazide – RH is an efficient and safe antihypertensive drug with all advantages of combined drugs. It has no less efficiency than the original drug with the same active components – CR in patients with mild to moderate hypertension. Convenience of taking – once per day – provides high compliance with treatment with this drug.

Synergism between corticosteroids and Rapamycin for the treatment of intraocular inflammation

The authors studied the combination effect of corticosteroids with the new immunosuppressant Rapamycin for the treatment of intraocular inflammation. A median-effect analysis, of the combined effect of Rapamycin and dexamethasone, was performed on the inhibition of lymphocyte proliferation in culture. The mathematical formulas allowed for the calculation of combination indices and dose-reduction factors. On the basis of these in-vitro results, treatment with reduced doses of drugs in combination was evaluated in the rat model of experimental autoimmune uveoretinitis. The results showed that Rapamycin and dexamethasone were synergistic over a wide concentration range. The calculated dose reduction factors indicated that an equivalent inhibition of lymphocyte proliferation was achieved with a combination of Rapamycin and dexamethasone reduced by 5-7 and 3-6 fold respectively, compared to the concentration required when each drug was used alone. In animals, there was a significant reduction of the incidence and severity of ocular inflammation with low doses of the drugs in combination. The authors conclude that the observed synergistic effect between Rapamycin and dexamethasone suggests that the use of this drug combination might be advantageous in the treatment of patients with severe uveitis.

Dose-response relationships for spironolactone in combination with a potassium-wasting diuretic.

The plasma and urine electrolyte responses to repeated doses of spironolactone, 25, 50, and 100 mg, in combination with metolazone, 2.5, 5.0, and 10 mg, were examined in 18 healthy subjects (six at each dose of metolazone). During the period of pharmacologic steady state, there were log linear spironolactone dose-response relationships for plasma potassium, sodium, and bicarbonate (P less than 0.001 in each case) with no contraindication to parallelism between the metolazone groups. In the absence of mineralocorticoid challenge, spironolactone dose-urine electrolyte responses could not be demonstrated. However, after fludrocortisone, spironolactone log dose-response trends were linear with respect to natriuresis (P = 0.027), antikaliuresis (P = 0.020), and log 10 Na/K (P = 0.001), which is usually considered the best single index of renal antimineralocorticoid activity, and exhibited parallelism between the metolazone doses. These observations suggest that a convenient bioassay for aldosterone antagonists in normal men may be provided by the electrolyte responses to repeated doses of such drugs in combination with potassium-wasting diuretics. In view of the limitations of other methods, this approach may have particular relevance to the evaluation of potassium-sparing properties.

Precautions in use of antihypertensive drugs, including chlorothiazide.

The aim in antihypertensive therapy should be to lower the blood pressure gradually by using the safest, mildest, and least symptomproducing drugs; dosages are determined by patient observation over weeks or months of time. One of the various preparations of Rauwolfia should be used first, an effort being made to achieve the antihypertensive effect without depression. A second drug, Veratrum, may be added if extensive trial has shown the first alone to be inadequate. Again an effort is made to lower the blood pressure without side-effects; in the case of Veratrum these are usually nausea and vomiting, rarely cardiac arrhythmia and collapse. A third drug to be tried with Rauwolfia is hydralazine; it is a potent hypotensive drug, but it can have acute and chronic toxic effects. The fourth is chlorothiazide, which can, in addition to a desirable hypotensive effect, cause diuresis and quickly deplete the body of potassium. The dosage should be kept low and supplements of potassium should be given in patients receiving long-term treatment. A fifth class of available drugs are the ganglionic blocking agents, the dosages of which are so critical that especially exacting care is needed in adapting them to the individual case. Each class of drug may be used in combination with the others, but every change should be instituted gradually. By use of minimal effective doses of drugs in combination, a safe antihypertensive regimen can generally be developed.

Subacute staphylococcus aureus endocarditis: recovery following combined antibiotic therapy

1. 1. A case of subacute bacterial endocarditis due to a penicillin-resistant, coagulase-positive Staph. aureus superimposed on chronic rheumatic valvular disease has been reported. 2. 2. Combination antibiotic therapy consisting of the simultaneous administration of penicillin, dihydrostreptomycin, and aureomycin for thirty-three days resulted in prompt clearing of the blood stream, progressive improvement, and the absence of any evidence of active infection when the patient was examined seven and sixteen months later. 3. 3. Treatment of similar cases with large doses of antibiotic drugs in combination is suggested.