•Infusion site extravasation injury is a rare but serious adverse event of tisotumab vedotin.•Central venous access device should be considered in patients with risk factors receiving antibody drug conjugate therapy.•Topical steroids may be used as part of supportive measures.

Phlebitis is a common complication of intravenous administration and greatly affects clinical outcomes, patient satisfaction, and health-care expenditure. Numerous studies have revealed venous injuries only through visual and histopathological examination. Although sporadic studies have explored the cellular and molecular biological mechanisms of phlebitis and the outcomes of pharmacological interventions, an updated review over the last decade is not available.

Progress in research on the mechanisms and interventions of phlebitis was summarized from the perspective of endothelial cells and signaling pathways by retrieving the PubMed, Web of Science Core Collection, MEDLINE, Embase, and CNKI.

Phlebitis involves multiple signaling pathways (eg, nuclear factor kappa B, Wnt/β-catenin, focal adhesion kinase/protein kinase B, Toll-like receptor, protein kinase C beta/NADPH oxidase, PI3K/AKT/TNF, and JAK2/STAT3), upregulation of E-selectin, GBP5/NLRP3 inflammasome axis, cell apoptosis, intracellular ROS generation, SOD reduction, stimulation of angiogenesis, and induction of autophagy-associated cell death. Preventive and curative interventions included α-solanine, baicalein, escin, intermedin, Y15, micro-ribonucleic acid-223, sotrastaurin, cimetidine, aescin, resveratrol, α-chaconine, Chahuang ointment, QingLuoTongMai, Mailuo Shutong, and N-acetylcysteine. Laboratory models included vascular endothelial cells, real-time cell-monitoring analysis, network pharmacology analysis and experimental verification in vivo, animal models of phlebitis (rat, rabbit, and mouse), rabbit models with peripherally inserted central catheters (PICC) catheterization, models of PICC/central venous catheter indwelling with combined drugs in human umbilical vein endothelial cells, and compatibility with endothelial cells. Factors affecting vascular endothelial cell injury include difference in the same class of drugs, concentration and exposure time of precipitant, and infusion strategy.

Phlebitis is accompanied by endothelial dysfunction and may involve multiple molecular and cellular mechanisms. These findings improve our understanding of the molecular targets of interventions and help identify effective candidates for the prophylaxis and treatment of phlebitis. Vascular health and risk management should be considered when initiating intravenous administration.

Enfortumab vedotin is an antibody drug conjugate approved for management of pretreated locally advanced or metastatic urothelial carcinoma, which is associated with a rare risk of drug extravasation and soft tissue reactions.

We report two cases of EV extravasation with subsequent development of bullae and cellulitis.

They were both treated for cellulitis and had conservative management without surgical intervention and were able to resume treatment with Enfortumab vedotin without subsequent adverse events.

We propose that EV acts as a vesicant upon extravasation, highlight measures to prevent extravasation events, and encourage appropriate measures when dealing such as attempt of aspiration, removal of catheter, application of compresses, and thorough documentation with photographic evidence.

Subcutaneous physiology is distinct from other parenteral routes that benefit the administration of prolonged-release formulations. A prolonged-release effect is particularly convenient for treating chronic diseases because it is associated with complex and often prolonged posologies. Therefore, drug-delivery systems focused on nanotechnology are proposed as alternatives that can overcome the limitations of current therapeutic regimens and improve therapeutic efficacy.

This review presents an updated systematization of nanosystems, focusing on their applications in highly prevalent chronic diseases. Subcutaneous-delivered nanosystem-based therapies comprehensively summarize nanosystems, drugs, and diseases and their advantages, limitations, and strategies to increase their translation into clinical applications. An outline of the potential contribution of quality-by-design (QbD) and artificial intelligence (AI) to the pharmaceutical development of nanosystems is presented.

Although recent academic research and development (R&D) advances in the subcutaneous delivery of nanosystems have exhibited promising results, pharmaceutical industries and regulatory agencies need to catch up. The lack of standardized methodologies for analyzing in vitro data from nanosystems for subcutaneous administration and subsequent in vivo correlation limits their access to clinical trials. There is an urgent need for regulatory agencies to develop methods that faithfully mimic subcutaneous administration and specific guidelines for evaluating nanosystems.

The administration of chemotherapy is a high-risk and nurse-sensitive practice. One complication is extravasation.

The purpose of this study was to determine the incidence of and iatrogenic factors associated with extravasation in the ambulatory and inpatient settings of a community cancer center.

Events were reviewed by agent, route of administration, patient characteristics, and RNs administering the agent. A one-year, retrospective review of electronic health records and pharmacy and nursing reports was conducted.

The number of vesicants, irritants, and irritants with vesicant properties administered was 12,260 in the ambulatory setting and 612 on the inpatient unit, with 21 and 1 extravasation events, respectively. Incidence rates for both settings were 0.001%. The most common agent to extravasate was docetaxel, and all events occurred via peripheral route. The incidence of events was lower than the reported benchmark for National Cancer Institute-designated cancer centers.

Chemotherapy extravasation can lead to serious patient harm in patients with cancer. For nurses who administer vesicant chemotherapy, extravasation is a primary concern. Regardless of nurse experience level and despite prevention strategies, extravasations occur. Literature related to nurse management of chemotherapy extravasation beyond initial treatment is lacking, and no descriptors are available for a formalized process. Communication gaps and a lack of standardized follow-up within a 1400-bed, quaternary care academic medical institution contributes to challenges in care continuity when patients transition between hospital and ambulatory settings. With chemotherapy extravasation, the site does not immediately exhibit signs of tissue injury, leading to a false sense of security. As a result, tissue damage can be significant by the time the patient returns for his or her regular appointment. Two oncology clinical nurse specialists (CNSs) recognized an opportunity to bridge the gap and overcome the challenges by addressing patient needs postextravasation. Between 2015 and 2016, a formal consult process was designed, approved, and implemented to observe, manage, and make recommendations for timely care and follow-up. Since implementation of the process, the oncology CNSs have received multiple requests for consultations. Nursing staff report increased comfort levels with this process in place. A formalized process for managing chemotherapy extravasations increases patient safety and patient and nurse satisfaction.

Carboplatin is a platinum chemotherapeutic agent commonly used in veterinary oncology that is currently classified as an irritant to local tissues when extravasated. To the authors' knowledge, there are no reports of vesicant injuries associated with carboplatin administration reported in the veterinary literature. In this case series, seven dogs are described to have experienced injuries following a suspected carboplatin extravasation resembling vesicant injuries a median of 7 days after carboplatin administration (range 4-15 days). Wounds healed with a variety of treatments, including medical management and/or surgical debridement, a median of 25.5 days (range 7-49 days) after observation of the suspected extravasation injury. There were no obvious similarities involving carboplatin administration among patients to explain why these reactions occurred. Extravasation injury should be considered a possible local complication associated with carboplatin chemotherapy.

Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small cell lung, prostate, gastric, head and neck, and ovarian cancers, as well as in the adjuvant setting for operable node-positive breast cancers. Although the true incidence of dermatological adverse events (AEs) in patients receiving taxanes is not known, and has never been prospectively analysed, they clearly represent one of the major AEs associated with these agents. With an increase in the occurrence of cutaneous AEs during treatment with novel targeted and immunological therapies when used in combination with taxanes, a thorough understanding of reactions attributable to this class is imperative. Moreover, identification and management of dermatological AEs is critical for maintaining the quality of life in cancer patients and for minimizing dose modifications of their antineoplastic regimen. This analysis represents a systematic review of the dermatological conditions reported with the use of these drugs, complemented by experience at comprehensive cancer centres. The conditions reported herein include skin, hair, and nail toxicities. Lastly, we describe the dermatological data available for the new, recently FDA-and EMA- approved, solvent-free nab-paclitaxel.

Extravasation, or leakage of vesicant drugs into subcutaneous tissues, causes serious complications such as induration and necrosis in chemotherapy-treated patients. As macroscopic observation may overlook symptoms during infusion, we focused on skin temperature changes at puncture sites and studied thermographic patterns related to induration or necrosis caused by extravasation.

Outpatients undergoing chemotherapy using peripheral intravenous catheters were enrolled in this prospective observational study. We filmed and classified infrared thermography movies of puncture sites during infusion; ultrasonography was also utilized at puncture sites to observe the subcutaneous condition. Multiple logistic regression analysis was performed to examine the association of thermographic patterns with induration or necrosis observed on the next chemotherapy day. Differences in patient characteristics, puncture sites, and infusions were analyzed by Mann-Whitney's U test and Fisher's exact test according to thermographic patterns.

Eight patients developed induration among 74 observations in 62 patients. Among six thermographic patterns, a fan-shaped lower temperature area gradually spreading from the puncture site (fan at puncture site) was significantly associated with induration. Ultrasonography revealed that catheters of patients with fan at puncture site remained in the vein at the end of infusion, indicating that the infusion probably leaked from the puncture site. Patients with fan at puncture site had no significant differences in characteristics and infusion conditions compared with those with the other five thermographic patterns.

We determined that fan at puncture site was related to induration caused by extravasation. Continuous thermographic observation may enable us to predict adverse events of chemotherapy.

The circulatory pathway for particles deposited outside of blood capillaries has not been well characterized for non-traditionally-delivered chemotherapeutics.

Blood and lymph pharmacokinetics of docetaxel (5 mg/kg) and carboplatin (14 and 28 mg/kg) following subcutaneous (s.c.) versus intravenous (i.v.) delivery were determined in a rodent model with catheterizations of both the thoracic lymphatic duct and jugular vein for prolonged synchronous blood and lymph sampling.

Subcutaneous docetaxel demonstrates preferential lymphatic accumulation based on the area under the time-concentration curve (AUC_0-24h) whereas i.v. docetaxel resulted in a greater plasma maximum concentration measured (C_max). The apparent elimination half-life (t_1/2) in lymph for docetaxel is greater following i.v. or s.c. delivery compared to t_1/2 in blood. Carboplatin demonstrates a dose-dependent increase in plasma C_max regardless of delivery route; the total carboplatin exposure over 24 h in lymph and plasma are comparable.

Subcutaneous docetaxel achieves lymphatic accumulation greater than that of i.v. delivery.

Esophageal cancer (EC) mostly affects the elderly population and is frequently diagnosed at an advanced stage. Self-expanding metal stents (SEMS) are the most popular mode of palliation, but they are associated with reocclusion caused by tumor growth. To overcome this problem, docetaxel (DTX)-loaded polyurethane formulations were prepared for stent application. The films were evaluated against the cancer cell lines, OE-19 and OE-21, and normal esophageal cell line Het-1A. The DTX and the formulations were evaluated in vitro for the cytotoxicity and in vivo in nude mice. It was found that DTX and the formulations have a weak activity against the EC cell lines and an even weaker activity against Het-1A cell line. Preliminary in vivo studies showed skin toxicity in nude mice necessitating modification of the formulation. Reevaluation in a mouse xenograft model resulted in toxicity at high dose formulations while the low dose formulation exhibited modest advantage over commercial IV formulation; however, there was no significant difference between the commercial IV and blank formulation. DTX combination with an anti-cancer agent having complementary mode of action and non-overlapping toxicity could yield better outcome in future.

The incidence and management of antitumoral compound extravasation that occurred in our medical day hospital unit were registered in a 10-year period.

A total of 114 episodes were consecutively recorded out of an estimated number of 211,948 administrations performed (0.05%). Type of compound, localization, timing, symptoms, treatment, resolution, or sequelae were documented.

Extravasations after anthracyclines (17/114), platinum compounds (34/114), vinca alkaloids (7/114), and taxanes (34/114) were more frequently associated with edema and erythema ± pain. Five cases of monoclonal antibodies extravasation were observed without sequelae. With the involvement of an interdisciplinary task force and the use of dedicated guidelines, conservative management was successful in all patients. In the great majority of cases, recovery was complete within 48 hours after antidote administration. The support of our pharmacy was crucial. Physiatric evaluation was considered in several cases. No patients required surgery.

We confirm that the adopted standardized approach to this event resulted in a satisfactory outcome and could be suggested as appropriate for managing extravasation in a large clinical context.

Intravenous paclitaxel has been underused in dogs due to severe and acute hypersensitivity reactions. Subcutaneous (SC) administration of paclitaxel and its safety are unknown. In this preliminary study, SC administration of paclitaxel was evaluated for hypersensitivity reactions and toxicity in 21 dogs with advanced cancer. Dogs received 1 to 5 paclitaxel doses, ranging from 85 to 170 mg/m(2), SC every 14 or 21 days. A total of 40 paclitaxel doses were administered and none of the 21 dogs developed systemic or acute local hypersensitivity reactions. Severe skin lesions at the injection site developed in 2 dogs after the 4th injection at the same location. Grade 4 neutropenia was observed in 50% of the dogs 5 days after the first treatment at 115 mg/m(2) (n = 14). Two animals developed Grade 5 diarrhea and died likely due to hemodynamic failure or sepsis. Paclitaxel can be administered SC in dogs with no hypersensitivity reaction.

Docetaxel is one of the most widely used anticancer drugs and an ideal candidate for the development of generic formulations to reduce the economic cost. However, the use of generic drugs is an issue of debate because studies of their safety and efficacy in comparison with the original drug are not required for approval. The aim of this study is to determine whether the change in the formulation of the original drug is responsible for the toxicity changes observed.

A retrospective study contrasts the incidence of acute infusion reactions and skin reactions to four different presentations of docetaxel including the original drug. These drugs differ in the amounts of excipients.

1.031 doses of docetaxel were administered to 268 patients. A total of 26 grade 3/4 infusion reactions were detected. Compared to the original formulation, the relative risk of acute infusion reaction was 3.74 (1.52-9.18, p = 0.002), 0.57 (0.19-1.64, p = 0.288) and 0.37 (0.1-1.34, p = 0.117) for the patients treated with drugs 2, 3 and 4. For the dermal toxicity, 9 % of patients suffered a clinically significant skin reaction. The relative risks of clinically significant dermal toxicity for the different formulations of docetaxel versus the original formulation were as follows: 6.15 (2.78-13.58) and 7.13 (3.24-15.69) for drugs 3 and 4 (p < 0.001).

Our study suggests that some toxic effects of docetaxel may be related to the excipients used in different formulations of the drug.