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Tracking small extracellular vesicles (sEVs), such as exosomes, requires staining them with dyes that penetrate their lipid bilayer, a process that leaves excess dye that needs to be mopped up to achieve high specificity. Current methods to remove superfluous dye have limitations, among them that they are time-intensive, carry the risk of losing sample and can require specialized equipment and materials. Here we present a fast, easy-to-use, and cost-free protocol for cleaning excess dye from stained sEV samples by adding their parental cells to the mixture to absorb the extra dye much like sponges do. Since sEVs are considered a next-generation drug delivery system, we further show the success of our approach at removing excess chemotherapeutic drug, daunorubicin, from the sEV solution., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Isaioglou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Acute myeloid leukemia (AML) treatment typically involves remission induction chemotherapy followed by consolidation chemotherapy. New treatments for AML have recently been introduced, including a chemotherapy formulation called CPX-351, which is administered via less time-intensive IV infusion than the standard "7 + 3" continuous infusion regimen of cytarabine plus an anthracycline. The purpose of this study was to estimate utilities that could be used in economic modeling of AML treatment. Materials and methods: In time trade-off interviews, participants from the UK general population valued 12 health states drafted based on literature and clinician interviews. To identify disutility associated with chemotherapy, two types of induction and four types of consolidation were added to an otherwise identical health state describing AML. The decrease in utility when adding these chemotherapy regimens represents the disutility of each regimen. Five additional health states were valued to estimate utilities associated with other AML treatments. Results: Two hundred participants completed interviews. Mean (SD) utilities were 0.55 (0.31) for pre-treatment AML and 0.66 (0.29) for AML in temporary remission. Adding any chemotherapy significantly decreased utility ( p  < 0.0001). Induction had a mean disutility of -0.11 with CPX-351 and -0.15 with 7 + 3. Mean disutility for consolidation ranged from -0.03 with outpatient CPX-351 to -0.11 with inpatient 5 + 2. Utilities are also reported for other AML treatments (e.g. transplant, low-intensity chemotherapy). Limitations: One limitation is that the differences in adverse event profiles between the treatment regimens were based on clinician opinion. Future use of CPX-351 in clinical trials or clinical settings will provide additional information on its adverse event profile. Conclusions: While all chemotherapy regimens were associated with disutility, regimens with shorter hospitalization and less time-intensive infusion were generally perceived as preferable. These utilities may be useful in cost-utility models comparing the value of AML treatments.

Purpose: Drug wastage is a major concern in oncology where costs of antineoplastic drugs are exorbitant, and the disposal of toxic drugs increases the chances of occupational hazards to healthcare and sanitary workers and environmental pollution at the site of disposal. The principal objective of this study was to ascertain the extent of drug wastage and calculate its financial costs., Materials and Methods: This was a prospective pilot study conducted to ascertain the quantity of drug wastage in a tertiary care hospital. This pilot study was conducted in day care and inpatient facilities in February 2016. The prescription of cytotoxic drugs, recommended dose, the quantity used, and remainder (waste) left were recorded from the nurses and pharmacy files of the hospital. Cost evaluation of the actual use and the waste was undertaken and an audit was conducted to understand in which anticancer drug the maximum wastage was generated., Results: The results of this study indicated that 6.1% of the total amount of reconstituted drugs was wasted. The highest drug wastage was observed in trastuzumab (29.55%), followed by etoposide (20.4%), dacarbazine (17.14%), daunorubicin (16.67%), and carboplatin (11.29%). Cost analysis showed that the total cost of the drug issued during the study period was Rs. 1,294,975 and the cost of drug wastage amounted to Rs. 143,820 (11.1%)., Conclusion: To the best of authors' knowledge, this is the first study from India and the results indicate that the financial impact of anticancer drug wastage was substantial. Attempts should be directed at minimizing the wastage and cost savings without risking patients' treatment regimen and administering effective dose schedule., Competing Interests: None

Aim: A comparative analysis of efficacy and toxicity of two chemotherapy regimens: standard German protocol ALL-BFM 90m and less intensive original test protocol ALL-MB 91 in a multicenter trial of acute lymphoblastic leukemia (ALL) in children., Material and Methods: In 1995-2002 a total of 834 patients with newly diagnosed ALL aged 0-18 years were admitted to 10 clinics of Russia. Of them, 713 were randomized in two groups: treatment program ALL-BFM 90m (n = 355) and ALL-MB 91 program (n = 358)., Results: In 7-year follow-up median, 10-year event-free survival (EFS) and overall survival (OS) did not differ significantly between the groups and was 67 +/- 3 and 68 +/- 3% (ALL-MB 91) and 74 +/- 2, 71 +/- 3% (ALL-BFM 90m), respectively. Though the rate of isolated recurrences in CNS in patients on the protocol ALL-MB 91 was 2.8%, they developed only in 0.8% patients of the standard risk group. Anemia, thrombocytopenia and agranulocytosis developed less frequently, hospital stay was significantly shorter on the test protocol vs the control one (p < 0.01)., Conclusion: EFS and OS on the test (ALL-MB 91) and control (ALL-BFM 90m) protocols were equivalent in lower toxicity and cost of therapy.

Background: Economic analyses of agents used in the treatment of AIDS and opportunistic diseases are particularly important in developing countries., Purpose: To analyze the cost-effectiveness of AIDS-related Kaposi's sarcoma (AIDS-KS) chemotherapy regimens in Brazil., Method: A decision-analysis model was developed, and effectiveness data were derived from randomized phase III trials evaluating pegylated liposomal doxorubicin (PLD), liposomal daunorubicin (DNX), and the ABV regimen (doxorubicin, bleomycin, and vincristine). Resource data on direct medical costs were obtained from local sources., Results: The cost-effectiveness estimates (defined as average costs per patient who responds completely or partially) favored PLD (US $10,272/responder) in comparison to DNX (US $16,263/responder). Regarding cost-effectiveness, the ABV regimen that is widely used in developing countries had better results when compared to both PLD (US $1,268 vs. US $10,271) and DNX (US $1,268 vs. US $16,260). The incremental cost per additional responder of using PLD instead of ABV was US $20,990. Sensitivity analyses suggest that these results hold over a wide range of assumptions., Conclusion: ABV seems to be the most reasonable treatment option for AIDS-KS patients in resource-limited countries like Brazil.

Pharmacoeconomic analyses are being used with greater frequency in clinical oncology trials. These analyses provide guidelines for prioritizing competing interventions and allocating health care resources, particularly when deciding whether to use a drug with a higher acquisition cost. For liposomal anthracyclines, the competing treatments are other liposomal anthracyclines and nonliposomal chemotherapy agents with similar activity. Pharmacoeconomic analyses of data from clinical trials in patients with Kaposi's sarcoma determined that the overall cost to achieve objective response was substantially lower with pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) than with liposomal daunorubicin (DaunoXome [DNX]). Additional economic analyses in patients with ovarian cancer showed that PLD has lower overall treatment costs than topotecan because it is administered less frequently and requires fewer interventions for toxicity. The decision to allocate health care resources to liposomal anthracycline treatment must therefore include consideration of cost-effectiveness and potential cost savings owing to improved tolerability.

Economic evaluations of new AIDS treatment drugs are important. For physicians treating patients with Kaposi's sarcoma, these issues are especially meaningful since cancer treatment costs for this group of patients are high. Kaposi's sarcoma is the most frequently occurring neoplasm in AIDS patients, affecting about 15% of this population. In our study, a retrospective economic evaluation has been made based on data from two randomized phase III clinical studies of severely immune-compromised HIV-infected individuals and which compares liposomal doxorubicin with liposomal daunorubicin. We have estimated the cost and cost effectiveness of the two drugs. The costs per complete or partial response are USS 18340 for daunorubicin and USS 8871 for doxorubicin. The incremental cost per additional responder by using liposomal doxorubicin instead of liposomal daunorubicin is USS 1910. Sensitivity analysis shows that these results hold over a wide range of assumptions.

Liposomal formulations have been shown to alter the efficacy and toxicity profiles of anthracylines for patients with HIV-related advanced Kaposi's sarcoma (KS). Using decision-analysis models, the costs and cost-effectiveness of the two U.S. Food and Drug Administration (FDA)-approved liposomal formulations of these agents were estimated. Estimates of costs, effectiveness, and cost-effectiveness were derived from clinical trial data of separate, randomized phase III trials of pegylated liposomal doxorubicin (20 mg/m2 every 3 weeks) and liposomal daunorubicin (40 mg/m2 every 2 weeks). Clinical response rates were 59% for pegylated liposomal doxorubicin and 25% for liposomal daunorubicin. Despite higher acquisition costs for pegylated liposomal doxorubicin, total estimated costs of treatment for KS and chemotherapy-related hematologic toxicities were similar ($7,066 U.S. compared with $6,621 U.S. for liposomal daunorubicin). Cost-effectiveness profiles, defined as average costs per responder, favored pegylated liposomal doxorubicin ($11,976 U.S./responder versus $26,483 U.S./responder for liposomal daunorubicin), reflecting the higher reported response rate in the phase III trial. Sensitivity analyses suggested that the costs and cost-effectiveness results would not differ markedly when evaluated over a range of assumptions, including response rate, neutropenia rate, and dosage variations.

Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P = 0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d; P < 0.0001) and thus patients required less time in hospital (mean 20 v 29 d) and less blood product support. 5-year relapse-free survival (28% v 23%; P = 0.05) and survival (23% v 18%; P < 0.05) were also better with DAT 3 + 10. Post-remission intensification of therapy with MAZE resulted in fewer relapses (66% v 74% at 5 years; P = 0.03) but patients allocated MAZE required considerably more supportive care and 14 (4.5%) died following 312 MAZE courses, whereas no deaths occurred following COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of outpatient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not only more effective than DAT 1 + 5, even for older patients, but is also less expensive; intensive post-remission therapy with MAZE achieves better leukaemic control but at the cost of substantial toxicity; whereas low-level maintenance therapy confers no apparent advantage in survival as well as being inconvenient and costly.

The use of new drugs in the treatment of AML could dramatically increase the cost of induction chemotherapy. To evaluate the cost-effectiveness of such new drugs, the overall cost to achieve complete remission (CR) with treatments including these drugs has to be compared to the cost of the daunorubicin-cytosine arabinoside (DNR-AraC) association, considered as the reference treatment. A retrospective analysis of charts from 15 patients treated with DNR-AraC was used to identify 228 items of cost, including general cost, diagnostic, supportive care, and chemotherapy. Eleven patients underwent CR after one course of chemotherapy for a cost of US$16,701 +/- 4451, and four patients achieved CR after two courses for a cost of US$37,130 +/- 4923. The chemotherapy represented only 1.4% of the total cost, supportive care 25% and general cost 56%. According to these data, the projective cost of a treatment with mitoxantrone instead of DNR was simulated in 40 untreated patients with AML. The better rate of CR obtained after one course of chemotherapy leads to a saving of 9% (US$1261) per patient, despite the higher cost of chemotherapy. Cost-effectiveness evaluation should be included in the clinical study of trials with new drugs.