Low-Dose MST-16/VP-16 Combination Chemotherapy in 9 Patients with Tumor Stage Mycosis Fungoides.

BACKGROUND/AIM: MST-16 and VP-16, both of which are topoisomerase II inhibitors, are antitumor agents regularly used to treat malignant lymphoma and small cell lung carcinoma. New therapeutic agents for tumor stage mycosis fungoides (MF) have recently been developed, but their efficacy is limited. We herein retrospectively reported the use of MST-16/VP-16 combination therapy for tumor stage MF at multiple treatment centers and examined their antitumor effect. METHODS: Five male and four female patients with tumor stage MF were enrolled. Age at the start of therapy ranged from 33 to 80 years (average: 54.5 years), and the previous treatment consisted of R-CHOP, CAVOP-IFN, etc. The protocol for low-dose MST-16/VP-16 combination chemotherapy consisted of 800 mg MST-16 and 25 mg VP-16 administered 5 days per month. RESULTS: Three of the 9 patients died, but two of the three fatalities were unrelated to MF. A treatment effect was seen in three and 6 patients who showed a complete response and a partial response, respectively. The 5-year and 10-year overall survival rate was 85.7% and 57.1%, respectively. Adverse reactions consisted of 4 cases of nausea and 1 case of leukopenia. CONCLUSION: The present study demonstrated that the response rate to MST-16/VP-16 combination therapy was 100% and that the treatment effect was relatively long, suggesting that this therapy may be a viable option for treating tumor stage MF.

Clinical features of long-term low-dose levetiracetam treatment for epilepsy.

BACKGROUND: The aim of this study was to assess the rate of response to long-term low-dose levetiracetam (LEV) treatment and the clinical factors associated with response. METHODS: The response to low-dose LEV of 43 patients with epilepsy (22 male, 21 female; age range, 5-39 years; median age, 13 years) was retrospectively assessed. Patients aged <15 years received <20 mg/kg/day LEV, whereas those aged ≥15 years received <1000 mg/day LEV. Clinical features were compared between responders to low-dose LEV, responders to the recommended dose, and non-responders. RESULTS: Of the 43 patients who received low-dose LEV, 13 (30%) showed improvement, defined as seizure cessation or >75% seizure reduction over 6 months for patients with monthly, weekly, and daily seizures; and over 1 year for patients with yearly seizures. Efficacy was maintained for >1 year in 10 (77%) of the 13 patients. Long-term response to low-dose LEV was significantly associated with older age at onset and fewer previous treatments with ineffective anti-epileptic drugs. All patients showing long-term response to low-dose LEV developed only focal seizures. CONCLUSIONS: Titration of LEV starting from a low dose may be effective in selected patients. Once patients respond to low-dose treatment, maintenance of the effective dosage may prolong response.

Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study.

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

Process Evaluation of a Double-Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra-Low-Dose Treatment for Hypertension Within a Federally Qualified Health Center Network (QUARTET USA).

BACKGROUND: This convergent parallel-design mixed-methods process evaluation of the QUARTET USA (Quadruple Ultra-Low-Dose Treatment for Hypertension USA) clinical trial (NCT03640312) explores patient and health care professional perceptions about the use of low-dose quadruple therapy (LDQT) as a novel strategy for hypertension management. METHODS AND RESULTS: A survey of all 62 patients enrolled in the QUARTET USA trial was conducted. A subsample of 13 patients and 11 health care professionals, recruited via purposive sampling, took part in semistructured interviews. At enrollment, 68% of participants (mean [SD] age, 51.7 [11.5] years; 56% self-identified as Hispanic: Mexican ethnicity, 16% as Hispanic: other ethnicity, 16% as Black race, 8% as White race, and 1.6% as South Asian race) reported that their current health depended on blood pressure medications, and 48% were concerned about blood pressure medications. At trial completion, 80% were satisfied with LDQT, 96% were certain the benefits of taking LDQT outweighed the disadvantages, and 96% reported that LDQT was convenient to take. Both patients and health care professionals found LDQT acceptable because it reduced patients' perceived pill burden and facilitated medication adherence. Health care professionals stated that a perceived limitation of LDQT was the inability to titrate doses. Steps to facilitate LDQT implementation include introducing stepped-care combinations and treatment protocols, inclusion in clinical practice guidelines, and eliminating patient cost barriers. CONCLUSIONS: LDQT was an acceptable strategy for hypertension treatment among patients and health care professionals involved in the QUARTET USA clinical trial. Although LDQT was generally perceived as beneficial for maintaining patients' blood pressure control and facilitating adherence, some clinicians perceived limitations in titration inflexibility, adverse effects, and costs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03640312.

Therapeutic and Prophylactic Use of Oral, Low-Dose IFNs in Species of Veterinary Interest: Back to the Future.

Cytokines are important molecules that orchestrate the immune response. Given their role, cytokines have been explored as drugs in immunotherapy in the fight against different pathological conditions such as bacterial and viral infections, autoimmune diseases, transplantation and cancer. One of the problems related to their administration consists in the definition of the correct dose to avoid severe side effects. In the 70s and 80s different studies demonstrated the efficacy of cytokines in veterinary medicine, but soon the investigations were abandoned in favor of more profitable drugs such as antibiotics. Recently, the World Health Organization has deeply discouraged the use of antibiotics in order to reduce the spread of multi-drug resistant microorganisms. In this respect, the use of cytokines to prevent or ameliorate infectious diseases has been highlighted, and several studies show the potential of their use in therapy and prophylaxis also in the veterinary field. In this review we aim to review the principles of cytokine treatments, mainly IFNs, and to update the experiences encountered in animals.

Comparison of the Effect of High and Low Doses of Adrenocorticotropic Hormone (ACTH) in the Management of Infantile Spasms.

OBJECTIVES: Infantile spasms can have irrecoverable adverse effects on a child's brain. Adrenocorticotropic hormone (ACTH) is the most common first-line medication for the treatment of infantile spasms. However, the suitable dose and duration of treatment continue to be debated among specialists. Since high doses of ACTH, which are commonly used, can produce more side effects, lower doses are preferred. The aim of this study was to determine the effect and extent of complications caused by high and low doses of ACTH in children with infantile spasms. MATERIALS & METHODS: This clinical trial was performed on 32 infants with infantile spasms, aged 1.5-18 months. The subjects were divided into high- and low-dose ACTH groups. Treatment continued for two months. The therapeutic effects and complications were then compared over 18 months. RESULTS: The results indicated no significant difference between the groups in terms of the short-term prognosis of convulsions, final prognosis of patients with spasm relapse, EEG changes after treatment, and post-treatment development of hypertension. On the other hand, there was a significant difference in the frequency distribution of restlessness intensity and becoming Cushingoid, which were more frequent in the high-dose group. CONCLUSION: The results indicated that high- and low-dose ACTH are equally effective in controlling spasms, yet the low dose causes fewer side effects.

Anti-Tumor Effects of Low Dose Zoledronate on Lung Cancer-Induced Spine Metastasis.

Zoledronate (Zol) is an anti-resorptive/tumoral agent used for the treatment of many cancers including spinal bone metastasis. High systemic administration of a single dose is now the standard clinical care, yet it has been associated with several side effects. Here, we aimed to evaluate the effects of lower doses Zol on lung cancer and lung cancer-induced bone metastasis cells over a longer time period. Human lung cancer (HCC827) and three bone metastases secondary to lung cancer (BML1, BML3 and BML4) cells were treated with Zol at 1, 3 and 10 µM for 7 days and then assessed for cell proliferation, migration, invasion and apoptosis. Low Zol treatment significantly decreased cell proliferation (1, 3 and 10 µM), migration (3 and 10 µM) and invasion (10 µM) while increasing apoptosis (10 µM) in lung cancer and metastatic cells. Our data exploits the potential of using low doses Zol for longer treatment periods and reinforces this approach as a new therapeutic regimen to impede the development of metastatic bone cancer while limiting severe side effects following high doses of systemic drug treatment.

The "Kiel Concept" of Long-Term Administration of Daily Low-Dose Sildenafil Initiated in the Immediate Post-Prostatectomy Period: Evaluation and Comparison With the International Literature on Penile Rehabilitation.

INTRODUCTION: Radical prostatectomy (RP) is the most common definitive invasive treatment option for localized prostate cancer. Although the different surgical procedures-open RP, laparoscopic RP, and robot-assisted laparoscopic RP-do not differ significantly for the results of postoperative erectile dysfunction (ED) and continence, the fear of losing erectile function (EF) is often an important factor for preoperatively sexually active men when deciding for or against a procedure. AIM: To review the available literature on rehabilitation of EF after RP and to evaluate the value of the "Kiel concept" against different strategies of phosphodiesterase type 5 inhibitor (PDE5i) low-dose treatments. METHODS: A review of the available literature up to January 2017 was undertaken using the key terms postsurgical ED, penile rehabilitation," PDE5i rehabilitation, and PDE5i daily dose treatment. MAIN OUTCOME MEASURES: As a main outcome measure we chose reviewed different concepts on the rehabilitation of EF after RP, taking into account the clinical background of the Kiel concept. RESULTS: The different therapeutic concepts for rehabilitation of EF after nerve-sparing RP are surprising. The most frequently applied method is application of different PDE5is. Despite different studies on efficacy, the issue of an optimal concept remains unresolved. The reason for this, among others, can be found in the difficulty of comparing different studies, which can vary with respect to the degree of nerve sparing, postoperative preservation of nocturnal erections, concomitant morbidity, and the number and experience of surgeons. CONCLUSION: In 86% of patients, the Kiel concept has been shown to support rehabilitation of EF after nerve-sparing RP with some form of therapeutic method. The Kiel concept is one therapeutic option among other comparable therapeutic options. Osmonov DK, Jünemann KP, Bannowsky A. The "Kiel Concept" of Long-Term Administration of Daily Low-Dose Sildenafil Initiated in the Immediate Post-Prostatectomy Period: Evaluation and Comparison With the International Literature on Penile Rehabilitation. Sex Med Rev 2017;5:387-392.

Longevity study with low doses of selegiline/(-)-deprenyl and (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP).

AIMS: The first longevity study demonstrating that rats treated with the MAO-B inhibitory dose of (-)-deprenyl (0.25mg/kg) lived significantly longer than their saline-treated peers was published in 1988, and corroborated in many papers. The recent findings that (-)-deprenyl is primarily a PEA-derived synthetic catecholaminergic activity enhancer substance; (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP) is a tryptamine-derived synthetic enhancer substance, initiated our first longevity study on rats with low enhancer doses of (-)-deprenyl and BPAP to test the enhancer effect's role in life extension. MAIN METHODS: We used the shuttle box technique for selecting the optimum doses of (-)-deprenyl and BPAP. (-)-Deprenyl exerts in rats in 0.001mg/kg its 'specific' enhancer effect and in 0.1mg/kg its 'non-specific' enhancer effect. BPAP exerts its 'specific' enhancer effect in 0.0001mg/kg and its 'non-specific' enhancer effect in 0.05mg/kg. Groups of male Wistar rats (N=40) were treated subcutaneously from their 10th week until death, three times weekly, with saline (0.5ml/kg), and the selected doses of (-)-deprenyl or BPAP, respectively. As an indicator of aging we tested the age-related changes in their learning ability. KEY FINDINGS: Rats treated with 0.0001 or 0.05mg/kg BPAP lived significantly longer than their saline treated peers (P<0.02) and BPAP was more potent in extending rats' lifespan than (-)-deprenyl. 18-month-old rats treated with 0.0001mg/kg BPAP were as good learners as 3-month-old saline treated rats. SIGNIFICANCE: The study revealed that the enhancer effect is responsible for life extension.