Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV, of BP-C1, a new anticancer substance.

UNLABELLED: A benzene-poly-carboxylic acid complex with cis-diammineplatinum(II) dihydrocholride, BP-C1 is currently used in clinical trials in treating metastatic breast cancer. BP-C1 controls tumor growth with a few mild side-effects, improving quality of life. METHODS: The data consisted of prospectively collected laboratory results from 47 patients in two controlled clinical trials of daily intramuscular injections of BP-C1 for 32 days. Study I was performed as an open, nonrandomized, Phase I dose-response, multicenter study with a three-level, between-patient, response surface pathway design. The second study was a randomized, double-blind, and placebo-controlled, multicenter study with a stratified semi-crossover design. RESULTS: Hemoglobin (Hb) and hematocrit (Hct) increased significantly (P<0.01) during BP-C1 treatment, while red blood cell (RBC) count increased but not significantly. The most pronounced increase in Hb, RBC, Hct, and white blood cell (WBC) was in anemic patients (P≤0.01). WBC count and neutrophils increased significantly (P=0.01) in the overall data. WBCs and neutrophils (P<0.01), eosinophils (P=0.05) and monocytes (P<0.01) increased significantly and markedly in patients with lowest baseline levels. Additionally, low levels of thrombocytes significantly increased. No changes in liver parameters, amylase, glucose, creatinine, or albumin, were detected except for albumin in the subgroup with low baseline levels, where levels increased significantly (P=0.04). An increase in K(+), Ca(2+), and PO4 (3-) was most pronounced in patients with low baseline levels (P≤0.02). A similar pattern detected for Mg(2+), prothrombin time (PT), coagulation factors II, VII, X (KFNT), and C-reactive protein (CRP), which increased significantly (P≤0.05) in the groups with the lowest values. CONCLUSION: Our findings support the safety profile of BP-C1 use in cancer patients. BP-C1 did not induce anemia, infection, bleeding, hepatic insufficiency or electrolyte imbalances. In contrast, BP-C1 corrected abnormalities. No hematological and biochemical toxicity was observed.

Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial.

BACKGROUND: Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required. METHODS: In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization. RESULTS: Of 245 patients who completed the month 12 visit, 235 patients (108 everolimus and 127 controls) entered the 12-month extension phase. At month 24, mean measured glomerular filtration rate had increased by 3.2±12.3 mL/min from the point of randomization in everolimus-treated patients and decreased by 2.4±9.0 mL/min in controls (P<0.001), a difference that was significant within both the heart and lung transplant subpopulations. During months 12 to 24, 5.6% of everolimus patients and 3.1% of controls experienced biopsy-proven acute rejection (P=0.76). There were no significant differences in the rate of adverse events or serious adverse events (including pneumonia) between groups during months 12 to 24. CONCLUSIONS: Converting maintenance thoracic transplant recipients to everolimus with low-exposure CNI results in a renal benefit that is sustained to 2 years postconversion, with significantly improved measured glomerular filtration rate in both heart and lung transplant patients. Despite reductions of more than 50% in CNI exposure, there was no marked loss of efficacy. The safety profile of the everolimus-based regimen was acceptable.

Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial.

BACKGROUND: The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. METHODS: In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate > or =20 mL/min/1.73m and <90 mL/min/1.73 m) >1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. RESULTS: Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (P<0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). CONCLUSION: Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.

Cyclosporine C2 levels have impact on incidence of rejection in de novo lung but not heart transplant recipients: the NOCTURNE study.

BACKGROUND: Cyclosporine (CsA) absorption varies early after transplantation and can be accurately assessed by the area under the absorption curve (AUC). The 2-hour post-dose (C2) level of CsA in whole blood is reported to be a useful surrogate marker of CsA AUC in kidney and liver transplant monitoring, but should be further explored in thoracic organ recipients. METHODS: In a 12-month study we included de novo lung (n = 95) and heart (n = 96) recipients. All participants received cyclosporine (Sandimmun Neoral) monitored by C0 and blood was collected for analysis of C2 retrospectively. Abbreviated AUC (AUC(0-4)) was measured at 7 days and 3 months. Primary outcome was C2 relation to the frequency of acute cellular rejection (ACR) needing treatment and possible decline in measured glomerular filtration rate (mGFR). Recipients were divided into lower, middle and upper third C2 groups based on 2-week post-operative values (tertiles T1 to T3). RESULTS: C2 was the most robust substitute for AUC(0-4) in the group of patients studied. For lung, but not heart, recipients there were differences in mean number of ACRs (p = 0.05), incidence of any rejections (p = 0.04), mean number of any rejections (p = 0.001) and time to first rejection (p = 0.03) between T1 and T3. C2 did not predict reduction in mGFR. CONCLUSIONS: C2 is a sensitive predictor for ACR in lung, but not heart, recipients, C2 was not predictive of a decline in mGFR. This study suggests that management of lung recipients by C2 may diminish the number of ACRs.