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Safety and efficacy of subcutaneous and continuous intravenous infusion rIL-2 in patients with metastatic renal cell carcinoma.

ABSTRACT: A retrospective analysis was conducted on data from four open-label, nonrandomised, phase II trials of recombinant interleukin-2 (rIL-2) in patients with metastatic renal cell carcinoma to compare the safety and efficacy of administration by subcutaneous (s.c.) and continuous intravenous (c.i.v.) infusion (n=103 s.c. and n=225 c.i.v.). No statistically significant differences were found between the cohorts in terms of overall response rate (s.c.: 13.6% vs c.i.v.: 12.4%, P=0.77), response duration (s.c.: 9.8 months vs c.i.v.: 10.1 months, P=0.99), and overall survival (P=0.08). Compared with c.i.v. administration, more patients in the s.c. cohort experienced stable disease (50.5 vs 29.8%) and fewer underwent disease progression (35.0 vs 43.6%). Subcutaneous administration was associated with a significantly lower incidence of grade 3 or 4 adverse events (46 vs 76%; P<0.001), and fewer s.c. patients required dose reductions because of toxicity (20 vs 82%). At the doses and within the schedules tested, this comparative analysis did not detect any difference in efficacy between s.c. and c.i.v. administration of rIL-2 in terms of overall survival, duration of response and response rate in patients with metastatic renal cell carcinoma. However, s.c. delivery of rIL-2 was associated with improved tolerability.

SUBMITTER: Geertsen PF

PROVIDER: S-EPMC2409650 | biostudies-other | 2004 Mar

REPOSITORIES: biostudies-other

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Efficacy and safety of sunitinib in elderly patients with metastatic renal cell carcinoma.

Project description:BackgroundWe retrospectively analyzed sunitinib outcome as a function of age in metastatic renal cell carcinoma (mRCC) patients.MethodsData were pooled from 1059 patients in six trials. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were compared by log-rank test between patients aged <70 (n=857; 81%) and ≥70 (n=202; 19%) years.ResultsIn first-line patients, median PFS was comparable in younger and older patients, 9.9 vs 11.0 months, respectively (HR, 0.89; 95% CI: 0.73-1.09; P=0.2629), as was median OS, 23.6 vs 25.6 months (HR, 0.93; 95% CI: 0.74-1.18; P=0.5442). Similarly, in cytokine-refractory patients, median PFS was 8.1 vs 8.4 months (HR, 0.79; 95% CI: 0.49-1.28; P=0.3350), while median OS was 20.2 vs 15.8 months (HR, 1.14; 95% CI: 0.73-1.79; P=0.5657). Some treatment-emergent adverse events were significantly less common in younger vs older patients, including fatigue (60% vs 69%), cough (20% vs 29%), peripheral edema (17% vs 27%), anemia (18% vs 25%), decreased appetite (13% vs 29%), and thrombocytopenia (16% vs 25%; all P<0.05). Hand-foot syndrome was more common in younger patients (32% vs 24%).ConclusionsAdvanced age should not be a deterrent to sunitinib therapy and elderly patients may achieve additional clinical benefit.

| S-EPMC3950861 | biostudies-literature

A Pharmacometric Framework for Axitinib Exposure, Efficacy, and Safety in Metastatic Renal Cell Carcinoma Patients.

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| S-EPMC5488123 | biostudies-literature

Efficacy of Vildagliptin Added to Continuous Subcutaneous Insulin Infusion (CSII) in Hospitalized Patients with Type 2 Diabetes.

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| S-EPMC7048888 | biostudies-literature

Phase I trial of systemic intravenous infusion of interleukin-13-Pseudomonas exotoxin in patients with metastatic adrenocortical carcinoma.

Project description:Adrenocortical carcinoma (ACC) is a rare but lethal malignancy without effective current therapy for metastatic disease. IL-13-PE is a recombinant cytotoxin consisting of human interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin A (PE). The main objectives of this Phase I dose-escalation trial were to assess the maximum-tolerated dose (MTD), safety, and pharmacokinetics (PK) of IL-13-PE in patients with metastatic ACC. Eligible patients had confirmed IL-13 receptor alpha 2 (IL-13Rα2) expressions in their tumors. IL-13-PE at dose of 1-2 μg/kg was administered intravenously (IV) on day 1, 3, and 5 in a 4-week cycle. Six patients received 1 μg/kg and two patients received 2 μg/kg of IL-13-PE. Dose-limiting toxicity was observed at 2 μg/kg, at which patients exhibited thrombocytopenia and renal insufficiency without requiring dialysis. PK analysis demonstrated that at MTD, the mean maximum serum concentration (Cmax ) of IL-13-PE was 21.0 ng/mL, and the terminal half-life of IL-13-PE was 30-39 min. Two (25%) of the eight patients had baseline neutralizing antibodies against PE. Three (75%) of the remaining four tested patients developed neutralizing antibodies against IL-13-PE within 14-28 days of initial treatment. Of the five patients treated at MTD and assessed for response, one patient had stable disease for 5.5 months before disease progression; the others progressed within 1-2 months. In conclusion, systemic IV administration of IL-13-PE is safe at 1 μg/kg. All tested patients developed high levels of neutralizing antibodies during IL-13-PE treatment. Use of strategies for immunodepletion before IL-13-PE treatment should be considered in future trials.

| S-EPMC4529344 | biostudies-literature

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Project description:A multicenter retrospective study was conducted to evaluate the efficacy and safety of cabozantinib in patients with advanced or metastatic renal cell carcinoma (mRCC). We enrolled 53 patients with mRCC who received cabozantinib at eight institutions in Japan. The primary endpoint was overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). In addition, we analyzed prognostic factors in patients with mRCC treated with cabozantinib. The median follow-up period was 8 months, and the median OS was 20.0 months. The ORR and DCR were 39.6% and 83.0%, respectively. The median PFS was 11.0 months. PFS was significantly shorter in patients previously treated with at least two tyrosine kinase inhibitors and in those with C-reactive protein (CRP) ≥ 1.27 mg/dL (p = 0.021 and p = 0.029, respectively). Adverse events of any grade and grades ≥3 occurred in 42 (79.2%) and 10 (18.9%) patients, respectively. Cabozantinib is a useful treatment option for patients with mRCC and may benefit from earlier use. In this study, CRP ≥ 1.27 mg/dL is a poor prognostic factor in patients treated with cabozantinib, and careful follow-up may be required in treating patients with high CRP.

| S-EPMC9775439 | biostudies-literature

Impact of Medicare Continuous Subcutaneous Insulin Infusion Policies in Patients With Type 1 Diabetes.

Project description:BackgroundThe Centers for Medicare and Medicaid Services (CMS) has numerous requirements for coverage of continuous subcutaneous insulin infusion (CSII; insulin pump). Due to recent improvements in diabetes treatment, people with type 1 diabetes are living longer, resulting in an increase in the number of individuals who are eligible for Medicare and are impacted by CMS policies regarding CSII.MethodsTwo hundred forty-one adults with type 1 diabetes who had been on CSII with CMS coverage for at least 6 months were surveyed. Median age was 67 years, mean A1c was 7.0%, 64% were women, 93% were white, and the median type 1 diabetes duration was 42 years. Participants reported median CSII use of 15 years and 82% were on CSII before starting CMS.ResultsOf those starting CSII while on CMS, challenges included cost of supplies (29%) or the insulin pump (24%). The majority (57.5%) reported issues with obtaining supplies, the most common problems being delays in release of supplies (29%), difficulty getting paperwork completed (23.5%), and seeing a health care provider every 90 days (18%). Participants reported changing their CSII behaviors because of supply delays (39%) including leaving site in place >3 days (64%), and reusing pump supplies (34%). Consequently, participants reported adverse outcomes including more erratic (48%) or higher (42%) blood glucose and pain or irritation at sites (34%).ConclusionThis study concluded that current CMS CSII policies promote adverse CSII behaviors and outcomes in type 1 diabetes and thus call for changes in the CMS CSII policies.

| S-EPMC7196863 | biostudies-literature

Efficacy and Safety of Sorafenib Therapy on Metastatic Renal Cell Carcinoma in Korean Patients: Results from a Retrospective Multicenter Study.

Project description:ObjectiveTo evaluate the efficacy and safety of sorafenib for Korean patients with metastatic renal cell carcinoma (mRCC).MethodsA total of 177 mRCC patients using sorafenib as first- (N = 116), second- (N = 43), and third-line (N = 18) therapies were enrolled from 11 Korean centers between 2006 and 2012. The patient characteristics, therapy duration, tumor response, disease control rate, and tolerability were assessed at baseline and at routine follow-ups, and the progression-free survival (PFS) and overall survival (OS) times and rates were analyzed.ResultsAmong all patients, 18 (10.2%) stopped sorafenib treatment for a median of 1.7 weeks, including 15 (8.5%) who discontinued the drug, while 40 (22.6%) and 12 (6.8%) patients required dose reductions and drug interruptions, respectively. Severe adverse events (AEs) or poor compliance was observed in 64 (36.2%) patients, with 118 (7.4%) ?grade 3 AEs. During the treatment, one myocardial infarction was observed. The number of ?grade 3 AEs in the first-line sorafenib group was 71 (6.8% of the total 1048 AEs). During a median follow-up of 17.2 months, the radiologically confirmed best objective response rate, disease control rate, median PFS, and median OS were 22.0%, 53.0%, 6.4 months (95% confidence interval [CI], 5.2-8.9), and 32.6 months (95% CI, 27.3-63.8) for the total 177 sorafenib-treated patients, respectively, and 23.2%, 56.0%, 7.4 months (95% CI, 5.5-10.5), and not reached yet (95% CI, 1.0-31.1) for the first-line sorafenib group, respectively.ConclusionsSorafenib produced tolerable safety, with a ?grade 3 AE rate of 7.4% and an acceptable disease control rate (53.0%) in Korean mRCC patients.

| S-EPMC4550402 | biostudies-literature

Efficacy and Safety of Subcutaneous Infusion of Non-formulated Furosemide in Patients with Worsening Heart Failure: a Real-World Study.

Project description:We aimed to evaluate the efficacy (short-term changes in surrogates of decongestion) and safety following the ambulatory administration of subcutaneous furosemide (SCF) in patients with WHF. Fifty-five ambulatory patients were treated with SCF administered by an elastomeric pump for at least 72 h. Surrogates of congestion were assessed at baseline, 72 h, and 30 days. Spot urinary sodium (uNa+) was assessed at baseline, 24-48-72 h, and 30 days. The median (IQI) of NT-proBNP and uNa+ at baseline was 5218 pg/mL (2856-10878) and 68±3 mmol/L, respectively. Following administration of SCF (median dose of 100 mg/daily), we found a sustained increase in uNa+ during the first 72 h of treatment compared to baseline, paralleled with evidence of decongestion at 72 h, and 30 days. No significant safety concerns were observed. SCF was an effective and safe diuretic strategy for outpatient congestion management. Non-formulated subcutaneous furosemide in patients with WHF. Efficacy and safety.

| S-EPMC9213343 | biostudies-literature

Phase III study of the efficacy and safety of subcutaneous versus intravenous tocilizumab monotherapy in patients with rheumatoid arthritis.

Project description:ObjectiveTo evaluate the efficacious noninferiority of subcutaneous tocilizumab injection (TCZ-SC) monotherapy to intravenous TCZ infusion (TCZ-IV) monotherapy in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to synthetic and/or biologic disease-modifying antirheumatic drugs (DMARDs).MethodsThis study had a double-blind, parallel-group, double-dummy, comparative phase III design. Patients were randomized to receive TCZ-SC 162 mg every 2 weeks or TCZ-IV 8 mg/kg every 4 weeks; no DMARDs were allowed during the study. The primary end point was to evaluate the noninferiority of TCZ-SC to TCZ-IV regarding the American College of Rheumatology criteria for 20% improvement in disease activity (ACR20) response rates at week 24 using an 18% noninferiority margin. Additional efficacy, safety, pharmacokinetic, and immunogenicity parameters were assessed.ResultsAt week 24, ACR20 response was achieved in 79.2% (95% confidence interval [95% CI] 72.9, 85.5) of the TCZ-SC group and in 88.5% (95% CI 83.4, 93.5) of the TCZ-IV group; the weighted difference was -9.4% (95% CI -17.6, -1.2), confirming the noninferiority of TCZ-SC to TCZ-IV. Remission rates of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate and the Clinical Disease Activity Index at week 24 were 49.7% and 16.4% in the TCZ-SC group and 62.2% and 23.1% in the TCZ-IV group, respectively. Serum trough TCZ concentrations were similar between the groups over time. Incidences of all adverse events and serious adverse events were 89.0% and 7.5% in the TCZ-SC group and 90.8% and 5.8% in the TCZ-IV group, respectively. Anti-TCZ antibodies were detected in 3.5% of the TCZ-SC group; no serious hypersensitivity was reported in these patients.ConclusionTCZ-SC monotherapy demonstrated comparable efficacy and safety to TCZ-IV monotherapy. TCZ-SC could provide additional treatment options for patients with RA.

| S-EPMC4225471 | biostudies-literature

Efficacy of temsirolimus in metastatic chromophobe renal cell carcinoma.

Project description:Renal cell carcinoma (RCC) is a histopathologically and molecularly heterogeneous disease with the chromophobe subtype (chRCC) accounting for approximately 5% of all cases. The median overall survival of advanced RCC has improved significantly since the advent of tyrosine kinase inhibitors and mammalian target of rapamycin (mTOR) inhibitors. However, high-quality evidence for the use of new generation tyrosine kinase inhibitors in patients with advanced chRCC is lacking. Few published case reports have highlighted the use of temsirolimus in chRCC.Here, we report the case of a 36-year-old Caucasian woman with metastatic chRCC with predominantly skeletal metastases who was refractory to sunitinib who demonstrated a durable clinical response to temsirolimus lasting 20 months. We review the available evidence pertaining to the use of new generation molecularly targeted agents, in particular mTOR inhibitors in chRCC and discuss their emerging role in the management of this disease which would aid the oncologists faced with the challenge of treating this rare type of RCC.Conducting randomised clinical trials in this rarer sub-group of patients would be challenging and our case report and the evidence reviewed would guide the physicians to make informed decision regarding the management of these patients.

| S-EPMC3679738 | biostudies-other

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