The patient was a 54-year-old woman with chronic myeloid leukemia. Ten months after treatment with dasatinib, she developed a cough. Imaging studies showed ground-glass patterns in the lower lung fields of both lungs, which led to suspicion of drug-induced lung injury and prompted discontinuation of dasatinib. A transbronchial lung biopsy showed epithelioid granuloma without necrosis in the alveolar region. There were no other systemic symptoms or signs to support a diagnosis of sarcoidosis. Fifteen days after withdrawal of dasatinib, both the cough and X-ray findings improved. Granulomatous tissue was detected on lung biopsy, which indicates that drug-induced sarcoidosis-like reaction (DISR) may cause interstitial lung injury as a respiratory complication of dasatinib treatment. Case reports of DISR following administration of immune checkpoint inhibitors and immunomodulatory drugs have recently become more frequent. Here we report a case of dasatinib-induced DISR with a review of the literature.

Non-clinical pharmacological safety studies are conducted using cells and animals to ensure the safety of pharmaceuticals in humans. Following these studies, drug candidates are administered to humans during clinical trials. Safety must be sufficiently confirmed in non-clinical studies to ensure that test participants suffer no adverse health effects. However, due to species differences, low ability to extrapolate from in vitro to in vivo evaluation methods, and other problems, health hazards may unfortunately still occur. Therefore, sophisticated in vitro evaluation systems using human cells are actively being pursued. The main challenge remains the lack of a reliable methodology for extrapolating in vitro results to in vivo settings. We have attempted to extract parameters that can be predictably translated from in vitro [contractile evaluation in three-dimensional (3D) heart tissue] to in vivo (guinea pig echocardiography) conditions, using cardiac contractile dysfunction induced by anticancer drugs as an example. In this review, we introduce the in vitro methods developed to date to evaluate this cardiac contractile dysfunction, analyze the factors enabling highly accurate prediction of torsades de pointes in humans based on past proarrhythmic risk prediction methods using human induced pluripotent stem cell-derived cardiomyocytes, and apply them to evaluate cardiac contractile dysfunction caused by anticancer drugs using three-dimensional heart tissue. We also introduce the proposed strategy for this evaluation method in this section.

We herein report the hair loss and recovery rates of patients treated with scalp cooling therapy at our hospital. Overall, 14 Japanese women with breast cancer who were scheduled to undergo chemotherapy and who used the Paxman Scalp Cooling SystemTM between May 2022 and May 2023 participated in our study. We retrospectively evaluated the efficacy of the scalp cooling therapy in preventing hair loss. We also assessed the extent of hair recovery at 1, 3, 6, and 12 months after chemotherapy using the scalp cooling therapy. Data were evaluated using the Dean scale. Post-chemotherapy, 8 patients (57.1%)experienced Grade 4 hair loss(defined as hair loss of >75%). No statistically significant difference was observed. A month after chemotherapy ended, the number of patients with Grade 4 hair loss reduced to 2/14(14.3%). No patient experienced Grade 4 hair loss after 3 months. By 6 months, all patients had recovered their pre-treatment hair volume. One year after chemotherapy, hair volume was sufficiently preserved. Our data indicate that scalp cooling during chemotherapy can reduce hair loss and accelerate hair regrowth.

Cardiovascular disease and dysfunction in cancer patients is often a medical problem. Cancer therapeutics related cardiac dysfunction(CTRCD)has long been known as late toxicity of anthracycline use and irradiation of the preserved breast and chest wall in breast cancer patients, CTRCD has received increasing attention, but there is still little evidence for prevention or prediction. Breast cancer has a good treatment outcome, and there is a need to address late cardiotoxicity. In recent years, the introduction of new drugs has forced us to deal with patients with new cardiotoxic and cardiovascular complications, such as myocarditis, which, combined with the increase in the number of cancer survivors with improved outcomes, has increased the number of situations requiring the concurrent consultation of oncologists and cardiologists. The goal is to improve life outcomes with optimal cancer treatment while reducing cardiac disease through appropriately timed interventions. Since drugs play different roles in initial treatment aiming for cure and palliative drug therapy for metastatic or recurrent breast cancer, cardiotoxicity should be discussed separately in close communication with cardiologists when considering the risk-benefit ratio. Discussions regarding the continuation of cardiac treatment and cancer treatment need to be done separately in'close collaboration'between oncologists and cardiologists.

With advancements in cancer treatment, the number of cancer survivors is increasing, underscoring the growing importance of cardio-oncology. For the safe and effective completion of cancer treatment, managing cardiovascular risk factors and cancer therapy-related cardiovascular complications is essential. Recently, several cardio-oncology clinical guidelines have been published both domestically and internationally. However, a significant evidence gap remains, as the majority of high-class recommendations are based on low-level supporting evidence. Additionally, the rapid advancements in both oncology and cardiology pose challenges in maintaining the relevance of guidelines. Therefore, interdisciplinary collaboration focused on the validity, feasibility, and sustainability of clinical practice guidelines is crucial for the future. Japan, as a super-aged society ahead of the rest of the world, could serve as a valuable source of real-world evidence, positioning itself as a global leader in education, clinical practice, and research in cardio-oncology.

A 65-year-old woman was diagnosed with hepatocellular carcinoma (HCC) in February 20XX-1. Following three cycles of transarterial chemoembolization (TACE) for recurrent HCC, combination therapy with atezolizumab and bevacizumab (Atezo+Beva) was initiated in February Y, 20XX. Eight days after treatment initiation (Y+8), the patient developed a fever and generalized malaise. By day 14 (Y+14), her symptoms worsened, prompting a visit to her primary physician, where a fever of 39°C was recorded. However, no hypoxemia was observed, and she was sent home. The following day (Y+15), she developed dyspnea and hypoxemia (SpO2 in the 80% range), and chest computed tomography (CT) revealed a hilar central alveolar infiltration. She was subsequently admitted to her previous hospital. Comprehensive evaluation led to a diagnosis of congestive heart failure associated with thyrotoxicosis. According to the IMbrave150 study, thyroid dysfunction occurs in 13.4% of patients receiving Atezo+Beva therapy;however, cases classified as Common Terminology Criteria for Adverse Events Grade 3 or higher, requiring hospitalization, are extremely rare, with an incidence of only 0.3%.

An 86-year-old man underwent laparoscopic ileocecal resection with lymph node dissection(pT3N0M0, Stage Ⅱa, Ly1a, V1a). The patient did not receive any adjuvant chemotherapy. Two years later, the patient was diagnosed with a recurrence at the anastomotic site(RAS mutant, HER2 negative, MSI-low). After 4 courses of FOLFOX plus bevacizumab, the patient was admitted for ileus. Preoperative echocardiography revealed an ejection fraction(EF)of 35% and BNP level of 562.2 pg/ mL. Therefore, asymptomatic cardiomyopathy was suspected because of bevacizumab administration. Although the last bevacizumab dose was administered within 2 weeks, we performed a laparoscopic tumor resection with lymph node dissection. Histological examination revealed colon cancer recurrence without lymph node metastasis. The patient was discharged on 19 POD without heart failure and had no recurrence of UFT/UZEL for 11 months. Three months after surgery, EF increased to 61% and BNP level was 14 pg/mL. VEGF inhibitors are associated with a very high risk of cardiomyopathy according to the ESC guidelines(2022). These side effects in conversion therapy for cancer should be carefully considered, even though they are rare.

Diterpenoid alkaloids are major pharmaceutically active constituents of Aconitum plants. In phytochemical investigations on Aconitum japonicum subsp. subcuneatum, Aconitum yesoense var. macroyesoens, and Delphinium elatum cv. Pacific Giant (Ranunclaceae), the structures of isolated C19- and C20-diterpenoid alkaloids were elucidated. Three aconitine-type C19-diterpenoid alkaloids, jesaconitine, aconitine, and mesaconitine, which are main components of A. japonicum subsp. subcuneatum, are significantly toxic to the central nervous system. However, lycoctonine-type C19-diterpenoid alkaloids and C20-diterpenoid alkaloids are less toxic. Several diterpenoid alkaloids from the genera Aconitum and Delphinium and their derivatives exhibited slight cytotoxic activity against several human tumor cell lines [A549 (lung carcinoma), DU145 (prostate carcinoma), MDA-MB-231 (triple-negative breast cancer), MCF-7 (estrogen receptor-positive, HER2-negative breast cancer), KB (identical to cervical carcinoma HeLa derived AV-3 cell line), and multidrug-resistant (MDR) subline KB-VIN]. In our course of studies on synthetic derivatives of the C19-diterpenoid alkaloids delcosine and delpheline and the C20-diterpenoid alkaloids lucidusculine, pseudokobusine, and kobusine, we found several derivatives showing significant cytotoxic activity and, thus, providing promising new leads for further development as antitumor agents. Notably, several diterpenoid alkaloids were more potent against MDR subline KB-VIN cells than the parental drug-sensitive KB cells. Among non-cytotoxic synthetic analogues, several lycoctonine-type C19-diterpenoid alkaloid derivatives effectively and significantly sensitized MDR cells to three anticancer drugs, paclitaxel, vincristine, and doxorubicin.

CPX-351 (Vyxeos®), a liposomal formulation used in the treatment of acute myeloid leukemia, has been associated with cutaneous adverse events, particularly purpura, in previous clinical trials. We present the case of a 73-year-old woman with refractory acute monocytic leukemia and leukemia cutis, who was treated with CPX-351 as salvage induction therapy. Following treatment, the extramedullary lesions resolved; however, some skin lesions developed into pustular eruptions. These pustules appeared during the neutropenic phase, and cultures ruled out infection, leading to the diagnosis of sterile pustulosis. Supportive care, including skin care measures and application of antibiotic ointment, allowed for continued treatment, and the pustules resolved after crusting. To our knowledge, this is the first reported case of sterile pustulosis associated with CPX-351 treatment, highlighting the importance of early detection and appropriate management of skin complications for the successful continuation of therapy.

Ixazomib (IXA) is a convenient oral anticancer drug; however, due to its fixed dosage, IXA tolerability among elderly Japanese individuals may be reduced. Therefore, this study aimed to clarify the difference in relative dose intensity (RDI) of IXA in IRd therapy in elderly patients. Between October 2018 and September 2023, patients who underwent IRd therapy (IXA, lenalidomide, and dexamethasone combination treatment) at Ogaki Municipal Hospital were enrolled in the study and categorized into two age groups: ≥75 years (group O, n=16) and <75 years (group Y, n=6). We retrospectively analyzed RDI of IXA, in IRd therapy. In addition, we evaluated the reasons for dose reduction or delayed treatment. The median initial IXA dose was 3 mg (range: 2.3-4 mg) and 4 mg (range: 3-4 mg) in group O and Y, respectively (p=0.122). The median RDI in group O (65.8%, range: 51.1-91.7%) was significantly lower than in group Y (93.3%, range: 80.5-100.0%) (p=0.002). Among them, anorexia was more common in group O than in group Y (p=0.049). In group O, dose adjustments were made due to anorexia (n=10), diarrhea (n=5), nausea (n=2), and fatigue (n=2). In group Y, adjustments were made due to diarrhea (n=2) and thrombocytopenia (n=1). Upon IXA (4 mg) administration, the rate of dose adjustments due to gastrointestinal symptoms were 75% and 17% in group O and Y, respectively (p=0.051). Overall, RDI was lower in group O owing to gastrointestinal symptoms. This suggests that the fixed IXA dosage (4 mg) is less tolerable in older individuals.

Emesis and vomiting are the most common adverse events related to trastuzumab deruxtecan(T-DXd). T-DXd is listed as a moderate emetogenic chemotherapy(MEC)agent in the latest guidelines for the appropriate use of antiemetic drugs in Japan; however, the National Comprehensive Cancer Network Guidelines regard it as a highly emetogenic chemotherapy (HEC)agent. We investigated the risk factors for chemotherapy-induced nausea and vomiting(CINV)associated with T-DXd by analyzing data from 40 patients with advanced breast cancer(median age, 56 years)were receiving T-DXd administration between June 2020 and July 2023. CINV was graded using CTCAE v5.0. All patients were treated with antiemetic therapy consisting of a 5-HT3 receptor antagonist(5-HT3RA)and dexamethasone(DEX); 3 patients also received an NK1 receptor antagonist(NK1RA). Emesis was observed in 23(57.5%)(Grade≥2 in 7), and vomiting in 2 patients(5.0%, Grade 1). Emesis occurred >1 day after T-DXd administration in 78.3% and lasted for ≥7 days in 69.6%. These symptoms may be characteristic of T-DXd-related CINV. Antiemetic therapy for CINV in HEC may be considered to control T-DXd-associated CINV in patients aged<50 years or in those who did not achieve sufficient curative effects with MEC.

The patient was a 70-year-old man who underwent distal gastrectomy for gastric carcinoma of the antrum. One year after surgery, the patient developed a recurrence in the cardia lymph nodes. Following chemotherapy, the patient underwent a total resection of the remnant stomach and recurrent lymph nodes 2 years and 10 months after the resection of the primary tumor. The patient was re-treated with chemotherapy following surgery; however, he relapsed again, and pembrolizumab was initiated. After the administration of the 10th round of chemotherapy, the patient suddenly developed thirst and polydipsia. Marked hyperglycemia(BS level, 900 mg/dL)and ketoacidosis were observed; therefore, the patient was diagnosed with fulminant type 1 diabetes mellitus. The patient's symptoms improved after insulin administration, and self-injection was initiated. The patient was treated with pembrolizumab for 2 years with no apparent recurrence. The incidence of type 1 diabetes mellitus as an irAE is approximately 0.5% in patients on pembrolizumab. Although this is a rare complication, early detection and therapeutic intervention are desirable, and attention in daily practice is necessary.

We report a case of retroperitoneal abscess due to penetration of colonic diverticulosis during chemotherapy for sigmoid colon cancer. The patient was a 56-year-old man who was outpatient for chronic rheumatoid arthritis and was diagnosed sigmoid colon cancer with multiple simultaneous liver and lung metastases. The antitumor drugs were effective and the primary tumor was resected, and chemotherapy was continued due to progression of liver metastasis. After the molecular targeted drug was changed to bevacizumab, the patient was hospitalized with a diagnosis of colonic diverticulitis and was discharged with conservative therapy. Two months after discharge, the patient was hospitalized due to fever and gait disorder. Abdominal CT scan revealed abscess(12×7 cm)around the right kidney extended to abscess(15×4 cm)along the right iliopsoas muscle to the right hip joint. The retroperitoneal cavity was drained through right lumbar region and right inguinal area, and the retroperitoneal abscess disappeared. The patient improved gait disorder and was discharged from the hospital. The retroperitoneal abscess caused after the administration of bevacizumab, was fortunately possible to eliminate the retroperitoneal abscess by performing incision and drainage from extraperitoneal cavity.

A 76-year-old man with advanced colorectal cancer was started on oral S-1 monotherapy as postoperative chemotherapy. He had dyspnea on exertion, and imaging studies revealed frosted shadows in the bilateral lower lung fields. Transbronchial lung biopsy showed thickening of the alveolar wall, infiltration of inflammatory cells. Based on clinical history and examination results, he was diagnosed interstitial pneumonia with caused by S-1. His respiratory distress on exertion was markedly improved by oral administration of prednisolone(PSL). Thereafter, S-1 medication was not resumed and the patient was followed up on an outpatient basis while the PSL was gradually reduced. According to the S-1 package insert, the frequency of interstitial pneumonia is 0.3%, regardless of the presence or absence of concomitant chemotherapy, so the incidence of S-1 monotherapy is considered to be even lower. In this study, we report a case of colorectal cancer with interstitial pneumonia during monotherapy with S-1, with a review of the literature.

Despite recent advances in chemotherapy with immune-checkpoint inhibitor(ICI), some patients may have to undergo surgery after the immune-related adverse events(irAE). We report here a case of a 61-year-old man who developed the irAE-related anastomotic stenosis after robotic gastrectomy for gastric cancer. Previously, he was diagnosed as double cancers of far-advanced hung cancer and gastric cancer. He was treated with ICI-based chemotherapy comprising CBDCA, PEM and pembrolizumab for lung cancer, and developed drug-induced pneumonia and dermatomyositis due to severe irAE. Stenosis was improved with steroid therapy. Until now, there has been no recurrence without symptoms in these 2 years.

The patient, a 70-year-old post-menopausal woman diagnosed with cT2N0M0, Stage ⅡA, triple-negative breast cancer (TNBC), received neoadjuvant chemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab. After 3 courses of chemotherapy, the patient experienced diarrhea over 10 times per day. The stool culture was negative for CD and cytomegalovirus antigens. A histological examination of the sigmoid colon and rectum using needle biopsy revealed lymphocytic infiltration of epithelial cells, apoptosis, and collagen band thickening, consistent with irAE-induced enteritis. We diagnosed diarrhea and colitis due to irAE and treated the patient with high-dose steroids according to the NCCN treatment guidelines. The diarrhea and fever resolved rapidly following steroid administration. Lymphocytic infiltration, apoptosis, and collagen bands in the epithelial cells of the biopsied mucosa are critical for diagnosing irAE-induced enteritis. PD-1-associated enterocolitis is rare, with laboratory findings often revealing only minor changes in the early disease stages. Diarrhea worsens if treatment is delayed, underscoring the importance of early diagnosis and prompt initiation of steroid therapy.

Fluoropyrimidines are one of the key drugs in cancer chemotherapy, but rare adverse events are difficult to diagnose and treat. Here we report a case who developed the relatively rare adverse events of rhabdomyolysis and refractory enteritis during S-1-based chemotherapy for gastric cancer. Because S-1 is frequently used in daily practice of cancer chemotherapy, we should always manage adverse events with detailed knowledge of rare and potentially serious adverse events.

We report a case of phenytoin(PHT)toxicity due to a drug interaction with capecitabine started as postoperative adjuvant chemotherapy for rectal cancer. Nevertheless the patient was able to complete 8 courses with therapeutic drug monitoring (TDM). Case: 42-year-old female, diagnosed with epilepsy at age 15, taking PHT. She started CAPOX therapy as postoperative adjuvant chemotherapy for recto-sigmoid colon cancer. 23 days after starting capecitabine, she presented with dizziness and weakness of the legs. She was diagnosed with PHT intoxication because her serum PHT concentration was elevated at 45.8 μg/mL. CAPOX therapy was continued with frequent serum PHT concentration measurements and dosage adjustment, and the planned 8 courses were completed. During the course of the treatment, there were no epileptic seizures or reappearance of PHT intoxication symptoms. In this case, we were able to safely administer CAPOX therapy with TDM.

Tumor-specific active drug release from macromolecular antitumor drugs after tumor delivery is critical to achieve efficient cellular uptake of the active drug, thereby ensuring therapeutic efficacy. Upon reaching the tumor tissue, protease-facilitated depegylation of pegylated zinc protoporphyrin with ester bonds between PEG and ZnPP (esPEG-ZnPP) occurs, leading to a faster cellular uptake and superior antitumor efficacy compared to PEG-ZnPP with ether bonds (etPEG-ZnPP). This finding provides a viable strategy for achieving efficient tumor-specific drug release by utilizing an ester linkage between PEG and antitumor drugs. Another strategy involves using styrene-maleic acid copolymer (SMA), an amphiphilic polymer. Drug-encapsulating SMA aggregates disintegrate upon interaction with cell membrane components, releasing the encapsulated active drug. The author has demonstrated an improvement in the tumor accumulation of SMA-based macromolecular drugs by conjugating pirarubicin (THP), an anthracycline antitumor drug, with SMA. Furthermore, by conjugating various molecular weights of N-(2-hydroxypropyl)methacrylamide (HPMA) to THP via a hydrazone bond (P-THP, DP-THP, and SP-THP), the author has established a positive correlation between HPMA molecular weight and therapeutic efficacy as well as toxicity. Notably, P-THPs release THP under acidic conditions within tumor tissue; however, this release occurs solely outside tumor cells due to HPMA-mediated inhibition of cellular uptake. The author is currently developing macromolecular anticancer drugs using albumin for the tumor-targeted release of anticancer agents both intra- and extracellularly. The strategic development of tumor-targeting macromolecular antitumor drugs based on a comprehensive understanding of polymer characteristics and the tumor-specific environment is imperative for effective cancer therapy.

Many anticancer drugs, including anthracycline drugs, pose a risk of cardiovascular damage as an adverse reaction. This can detrimentally impact the prognosis and quality of life of patients, potentially leading to the interruption of cancer chemotherapy and compromising cancer treatment. Recently, onco-cardiology (or cardio-oncology) has developed as a new interdisciplinary field that focuses on the prevention and treatment of cardiovascular toxicity of anticancer drugs. In this review, we explore the mechanism underlying the cardiotoxicity of anthracyclines and examine pharmacological agents that safeguard the heart from anthracycline-induced damage. Anthracycline-induced cardiotoxicity primarily involves oxidative stress, characterized by radical production in mitochondria and subsequent apoptosis in cardiomyocytes. While various antioxidant agents, such as resveratrol, vitamin E, and melatonin have demonstrated efficacy in reducing anthracycline-induced cardiotoxicity in animal models, their clinical effectiveness remains inconclusive. Alternatively, dexrazoxane, an intracellular iron chelator, along with standard heart failure medications, such as β-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers, reduce anthracycline cardiotoxicity and prevent subsequent heart failure in both animal and human studies. Additionally, statins [hydroxymethylglutaryl (HMG)-CoA reductase inhibitors] and ranolazine have emerged as potential candidates for attenuating anthracycline-induced cardiotoxicity in clinical settings. Notably, recent in vitro findings suggest that everolimus, an autophagy/mitophagy-inducing antitumor drug, may protect cardiomyocytes from anthracycline-induced toxicity without reducing the antitumor effects of anthracycline. Although promising, further clinical research is warranted to validate the potential of everolimus as a safer and more effective anthracycline chemotherapeutic strategy.