In Japan, amrubicin hydrochloride (AMR) is occasionally administered to patients with recurrent small cell lung cancer (SCLC). AMR therapy can induce febrile neutropenia (FN), a complication that may be fatal or compromise therapeutic efficacy due to treatment interruption or dose reduction. Identifying risk factors for FN is therefore critical to ensuring safe and effective AMR administration. Current evidence on this issue remains limited to small case series, underscoring the need for more robust studies. We conducted a multicenter retrospective analysis to examine predictors of FN during AMR treatment for recurrent SCLC. Patients who received AMR between April 1, 2013, and March 31, 2023, were included. The cohort comprised 256 patients, divided into 192 without FN and 64 with FN. Multivariate analysis demonstrated that performance status (PS) >2 (odds ratio: 5.8, 95% confidence interval: 1.70-19.80, p=0.005) and hematocrit (HCT) (odds ratio: 0.93, 95% confidence interval: 0.877-0.994, p=0.033) were significantly associated with FN development. These findings suggest that PS and HCT may serve as key indicators for predicting FN during AMR therapy in patients with recurrent SCLC.

Chemotherapy-induced peripheral neuropathy (CIPN) frequently develops following treatment of cancer with cytotoxic chemotherapeutics, such as taxanes, platinum-containing agents and vinca alkaloids, and leads to impairment of patients' QOL and dose limitation or cessation of chemotherapy in the worst-case scenario. We have demonstrated that extracellular release of high mobility group box 1 (HMGB1), a nuclear protein, plays a critical role in the developmental process of CIPN, and that thrombomodulin alfa (TMα) capable of degrading HMGB1 in a thrombin-dependent manner prevents CIPN development. Our retrospective cohort study in female patients with breast cancer or gynecological cancer undergoing paclitaxel-based chemotherapy has shown that postmenopausal estrogen decline is a risk factor for the development or aggravation of CIPN. We have also demonstrated that ovariectomy aggravates CIPN in laboratory animals treated with paclitaxel, which is prevented by estrogen supplementation or treatment with TMα. On the other hand, there is evidence from animal studies for inhibition of CIPN by progesterone and of neuropathic pain by androgen. Together, different sex hormones including estrogen may function to limit the development of CIPN, while age-related decline of sex hormones could be a risk for CIPN development. Our study to clarify the effects of sex hormones on HMGB1 behavior during the developmental process of CIPN is still in progress, but we nonetheless propose that TMα capable of inactivating HMGB1 is useful in preventive intervention for cancer patients with high risk of CIPN, e.g., postmenopausal females.

A 74‒year‒old male was diagnosed with advanced rectal cancer with bowel obstruction, and abscess formation. After sigmoid colostomy, FOLFOXIRI plus bevacizumab as preoperative chemotherapy was initiated. On day 3, during continuous administration of 5‒fluorouracil(5‒FU), the patient developed impaired consciousness accompanied by convulsive seizures and conjugate deviation. Electroencephalography(EEG)revealed no epileptic discharges, and imaging studies revealed no abnormality. A blood test showed a high ammonia level of 367μmol/L. In the absence of prior liver disease, the cause was suspected to be due to high‒dose 5‒FU. Administration of lactulose was started. The ammonia level normalized and the consciousness recovered quickly by the following day. It was thought that chemotherapy would be difficult to continue, and 1 month later, robot‒assisted low anterior resection and ileostomy were performed. The patient was discharged home without complication on postoperative day 13. We report this case of advanced rectal cancer in which administration of high‒dose 5‒FU caused hyperammonemia accompanied by impaired consciousness, with a literature review.

This study investigated the increase in blood concentration of methotrexate (MTX) due to delayed elimination when a dipeptidyl peptidase-4 (DPP-4) inhibitors with organic anion transporter 3 (OAT3) inhibitory effects was co-administered with high-dose methotrexate therapy (HD-MTX). During the study period, five patients received a DPP-4 inhibitors. Delayed MTX elimination was confirmed in two of these patients 48 hours after the start of MTX administration. Both patients had received a DPP-4 inhibitors with OAT3 inhibitory effects. Previous literature has reported that MTX elimination may be delayed by the co-administration of drugs that have OAT3 inhibitory effects, but no reports have addressed the impact on actual blood concentration. This study suggests that co-administration of a DPP-4 inhibitors with OAT3 inhibitory effects during HD-MTX may contribute to an increase in blood MTX concentration 48 hours after the start of MTX administration. When conducting HD-MTX therapy, consideration should be given to switching to an alternative treatment.

Gastrointestinal perforation during chemotherapy for gastric cancer is an infrequent but important adverse event. We report a case of ileal ulcer perforation induced S-1 chemotherapy for gastric cancer. A 73-year-old male underwent total gastrectomy in December 2020(palliative surgery)and S-1 chemotherapy was initiated in January 2021. The treatment was well tolerated until late March, when he presented with sudden abdominal pain and fever. He was diagnosed with perforation of the gastrointestinal tract and acute generalized peritonitis. Emergency laparotomy revealed a 2-mm perforation in the ileum, approximately 30 cm proximal to the terminal ileum. About 7 cm of ileum including the perforated area was partially resected. Histopathological analysis confirmed a Ul-Ⅳ ulcer with granulation tissue and severe inflammation. Based on clinical and pathological findings, the perforation was attributed to S-1-induced small intestinal ulceration. The patient subsequently received up to fourth-line chemotherapy. He survived for 15 months after the initial surgery.

Fluoropyrimidine anticancer agents, exemplified by 5-fluorouracil (5-FU), induce severe adverse effects-such as myelosuppression, emesis, diarrhea, and hand-foot syndrome-in approximately 10-30% of patients. As such toxicities can result in delays or discontinuation of therapy, accurate prediction of drug response prior to treatment initiation is of critical importance. The metabolic degradation of 5-FU is primarily mediated by the drug-metabolizing enzymes dihydropyrimidine dehydrogenase (DPD) and dihydropyrimidinase (DHPase). These enzymes are encoded by the DPYD and DPYS genes, respectively; polymorphisms in these genes that reduce or abolish enzymatic activity lead to elevated systemic concentrations of 5-FU, thereby increasing the risk of severe toxicity. In Caucasian populations, four DPYD polymorphisms have been identified as predictive markers of adverse drug reactions. However, these variants are rarely observed in Japanese individuals, and reliable pharmacogenomic biomarkers remain largely unreported in this population. To address this gap, we conducted a comprehensive in vitro functional analysis of DPD and DHPase activity of DPYD and DPYS variants identified through large-scale whole-genome sequencing databases. This review summarizes our findings and elucidates the underlying mechanisms affecting the function of 5-FU-metabolizing enzymes, as revealed by our prior research.

Based on the POTENT trial results, S-1, an oral fluoropyrimidine, is used in the adjuvant setting for various cancers, including hormone receptor-positive and HER2-negative breast cancers. Although S-1 is generally well tolerated, rare but serious adverse effects, such as rhabdomyolysis, have been reported. We present a case of suspected S-1-induced rhabdomyolysis in a 56-year-old woman with a history of hypertension and dyslipidemia, who was taking amlodipine besilate and pravastatin sodium. Sixteen months prior, she underwent nipple-sparing mastectomy with axillary dissection and TRAM flap reconstruction for right breast cancer. Following dose-dense EC therapy and discontinuation of docetaxel owing to drug-induced pneumonitis, she began adjuvant therapy with letrozole and S-1. Serum creatine kinase(CK)level progressively increased, peaking at 4,419 U/L during the 14th course, accompanied by myalgia. After discontinuation of S-1, the CK level returned to normal despite the continuation of other medications. No other obvious cause of rhabdomyolysis was identified. Given the temporal relationship and resolution upon drug withdrawal, S-1 was considered the likely causative agent. Although extremely rare, clinicians should be aware of the potential for S-1-induced rhabdomyolysis and monitor for muscle-related symptoms during treatment.

A 75-year-old man diagnosed with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia did not respond to standard induction chemotherapy, but was successfully treated with inotuzumab ozogamicin (InO). Although ascites developed after three cycles of InO, the clinical criteria for sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD) were not met due to the absence of jaundice and hepatomegaly. However, an increase in the HokUS-6 score from 1 to 4 led us to discontinue InO, considering the risk of SOS/VOD. Three months later, the ascites recurred and a transjugular liver biopsy (TJLB) was performed, resulting in a pathological diagnosis of SOS/VOD. Although the symptoms associated with SOS/VOD temporarily improved with recombinant thrombomodulin and other supportive care, the ascites returned 1 month later along with jaundice. The patient died of liver failure progression that showed no improvement with defibrotide. Pathological examination at autopsy revealed enlarged endothelial cells and fibrosis of the central hepatic vein. In cases where the diagnosis of SOS/VOD is inconclusive based on clinical findings and HokUS scores, TJLB may facilitate earlier diagnosis and effective therapeutic decision-making for SOS/VOD.

Oral complications arising from cancer pharmacotherapy can profoundly impair patients' quality of life and potentially hinder the continuity and efficacy of cancer treatment. Proactive oral healthcare is essential in mitigating the incidence and severity of these complications, thereby facilitating oral functions such as eating and speaking, and sustaining patients' overall well-being. Accordingly, it is strongly recommended that dental professionals engage in oral management as part of the multidisciplinary cancer care team, beginning prior to the initiation of cancer therapy. However, due to the limited number of dental professionals working within hospital settings, collaboration with community-based dental clinics is frequently required. Moreover, interdisciplinary cooperation with nurses, pharmacists, and other healthcare professionals is indispensable to ensure the provision of high-quality oral healthcare. We contend that by harnessing the specialized knowledge of each discipline within a collaborative framework, the standard of oral care can be elevated, ultimately contributing to improved patient quality of life and enhanced therapeutic outcomes.

Patient 1 was a 65-year-old woman diagnosed with chronic myeloid leukemia (CML) in 2016. She was treated with dasatinib at a dose of 100 mg. After achievement of deep molecular remission (DMR) in 2018, the dasatinib dose was decreased to 50 mg a day. In April 2021, the patient suddenly developed high fever, skin swelling and redness, muscle swelling, and pain in bilateral lower extremities. Detection of G type hemolytic streptococcus in blood culture led to a diagnosis of streptococcal toxic shock syndrome (STSS). The patient recovered from disseminated intravascular coagulation and multiple organ failure by treatment with several antibiotics, fresh frozen plasma (FFP), and plasma exchange over a period of 2 months. Patient 2 was a 53-year-old man who developed CML in 2011. He was prescribed nilotinib, but efficacy could not be evaluated due to poor treatment adherence. Treatment with dasatinib was started instead within a year. DMR was achieved, but the patient developed STSS in July 2021. Both of these cases of STSS occurred in patients treated with dasatinib, which suggests that STSS may be related to dasatinib treatment in CML patients. We conducted a literature review to determine whether CML treatment selection was appropriate in these patients.

The effectiveness of scalp cooling systems (SC) for preventing hair loss during perioperative chemotherapy for breast cancer has been reported; however, few studies have evaluated their efficacy in elderly patients. From January 2018 to December 2022, at Matsue Red Cross Hospital, the efficacy of SC (Paxman Scalp Cooling System), combined with chemotherapy, in elderly patients (≥65 years, 14 cases) was compared with that in younger patients (<65 years, 30 cases). The percentage of patients with hair loss reduced to ≤50% postchemotherapy was 71.4% in the elderly group and 66.7% in the younger group. Three months postchemotherapy, all patients in both the groups had hair regrowth, no elderly patients discontinued treatment because of adverse events, and in a survey conducted 3 months postchemotherapy, 71% of the elderly patients indicated that they would recommend SC to others. With advances in supportive care, more elderly patients are receiving perioperative chemotherapy, and SC has been demonstrated to be useful for maintaining QOL even among elderly patients.

We describe the cases of 4 patients with breast cancer who developed an allergy to fosnetupitant (Pro‒NETU). Case 1: A 67‒year‒old woman with breast cancer and bone metastasis received premedication that included Pro‒NETU. Minutes after administration, she complained of flushing, tachycardia, and dyspnea. Administration was discontinued. Minutes after discontinuation, the patient's symptoms were alleviated. She experienced no further complaints of such symptoms, and her premedication subsequently excluded Pro‒NETU. Case 2: A 50‒year‒old woman with early stage breast cancer received premedication that included Pro‒NETU. Minutes after administration, she complained of flushing, dyspnea, and drowsiness. Administration was discontinued. Minutes after discontinuation, her symptoms ameliorated. Case 3: A 41‒year‒old woman with early stage breast cancer received premedication that included Pro‒NETU. Minutes after administration, she complained of flushing, tachycardia, and dyspnea. Administration was thus discontinued, and she received an H2‒blocker and corticosteroid. Minutes after discontinuation, her symptoms were alleviated. Case 4: A 50‒year‒old woman with early stage breast cancer received premedication that included Pro‒NETU. Minutes after administration, she complained of flushing and tachycardia. Administration was discontinued. Minutes after discontinuation, her symptoms ameliorated. Fosaprepitant did not cause these allergies. The patients in cases 2, 3, and 4 had known allergies to docetaxel, and the cause of allergy in case 4 was unknown. Polysorbate 80, contained in docetaxel, fosaprepitant, and Pro‒NETU, was suspected to be the cause of allergy in cases 1, 2, and 3.

The Ser/Thr-specific kinase, polo-like kinase 1 (Plk1), is a crucial eukaryotic cell cycle regulatory protein. Overexpression of this kinase is observed in many cancer cells and where it can be related to their aggressiveness. Dysfunction of Plk1 in cancer cells causes mitotic arrest and subsequent apoptosis. Accordingly, Plk1 is considered as a target for the development of anti-cancer agents. Plk1 has two domains, a catalytic kinase domain (KD) and a polo-box domain (PBD). PBD intramolecularly interacts with its KD and regulates Plk1 activity and localization. Therefore, in addition to the KD, the PBD is considered to be a potential drug target. We have been developing peptidic low-nanomolar-affinity PBD-binding inhibitors. However, these peptides do not show significant cytotoxicity, due to their low cell membrane permeability. To obtain cell-active Plk1 inhibitors, I applied a bivalent approach designed to simultaneously engage both KD and PBD regions of Plk1 for enhancing the potency, selectivity and lipophilicity. Here, I developed bivalent Plk1 inhibitors, in which the PBD-binding peptides are conjugated with the known KD-binding inhibitors BI2536 or wortmannin using PEG linkers. These bivalent inhibitors exhibit up to 100-fold enhanced Plk1 affinity relative to the best monovalent PBD-binding ligands, higher selectivity for tested kinases compared to BI2536, and significant cytotoxicity against HeLa cells.

In cancer drug therapy involving anti-epidermal growth factor receptor (EGFR) antibody drugs, skin disorders such as acneiform rash are frequently observed and often progress to severe forms, resulting in treatment discontinuation. The severity of these skin disorders has been reported to correlate with therapeutic efficacy. Therefore, appropriate management is essential to avoid interruption of treatment due to severe dermatological toxicity. Identifying patients at risk of developing serious skin disorders at the start of anti-EGFR antibody drug therapy is necessary to enable prophylactic or early intervention. However, risk factors for skin disorders induced by anti-EGFR antibody drugs remain poorly understood, and predicting the severity of these conditions is challenging. This review highlights findings from retrospective and prospective observational studies conducted to predict the severity of skin disorders associated with anti-EGFR antibody drugs.

High-dose methotrexate (MTX) therapy was developed nearly 50 years ago with the introduction of leucovorin (LV) rescue. Since then, its dosing and administration have been optimized for different diseases, subtypes, and risk groups. Important supportive modalities that are still in use today, such as high-volume hydration, alkalinization, and LV rescue, were established as high-dose MTX protocols were being developed. Glucarpidase (GCP), which directly hydrolyzes extracellular MTX, is now available in Japan as well. GCP can prevent or reduce complications, especially in patients with severely delayed MTX elimination or renal injury. The primary function of GCP is to avert or mitigate complications arising from excessive extracellular MTX. Due to the importance of conventional supportive care, it is crucial to be well-versed in its history and evidence.

Advances in leukemia treatment have significantly increased the number of long-term survivors, highlighting the importance of managing late complications. Osteonecrosis and osteoporosis are major skeletal complications that can severely impair quality of life. Osteonecrosis frequently occurs in adolescents and young adults and is associated with treatments such as corticosteroids and asparaginase. Although no established preventive strategy exists, intermittent dexamethasone dosing has been linked to lower incidence. Osteoporosis characterized by ischemic necrosis is associated with decreased bone mineral density and increased risk of fragility fractures, influenced by multiple factors including the disease itself, medications, nutrition, and physical inactivity. Early evaluation and risk-based management are essential for both conditions. In addition, bone pain or fractures may be the only initial symptom of leukemia, and the patient may have bone density loss before diagnosis. Comprehensive strategies for early detection, prevention, and intervention are urgently needed. Standardized assessment tools and prospective studies are critical to improving outcomes for bone complications in leukemia survivors.

Recent advances in cancer therapy have improved the long-term outcomes of cancer patients, increasing the importance of managing cardiovascular complications arising not only from cancer itself but also from chemotherapy, radiation therapy, and immunotherapy. In the field of hematology, there are serious concerns about cardiovascular complications of various chemotherapeutic agents such as anthracyclines, immunomodulatory drugs, BCR-ABL tyrosine kinase inhibitors, proteasome inhibitors, and immune checkpoint inhibitors. Chemotherapy has a wide variety of effects on the cardiovascular system, and the molecular mechanisms underlying the cardiovascular toxicities of individual molecularly targeted agents remain to be precisely defined. This "Onco-Cardiology" approach is expected to enhance interdisciplinary collaboration between oncology/hematology and cardiology specialists across clinical practice, research, and education to protect cancer patients and survivors from cardiovascular complications.

Cancer patients who develop cardiovascular complications have significantly lower survival rates due to their inability to continue appropriate cancer treatment. Onco-cardiology is an interdisciplinary area in which cardiologists and oncologists collaborate to optimize cancer treatment. The goal is to improve the prognosis and quality of life of cancer patients by ensuring that they can continue cancer treatment with appropriate cardiac management. When cardiotoxic anticancer drugs will be used, the oncologist should assess the patient's risk and cardiac function before starting treatment, and adjust treatment based on risk factors. During treatment, cardiac evaluation should be performed according to the patient's risk. Echocardiographic left ventricular ejection fraction (LVEF) is used to assess cancer treatment-related cardiac dysfunction (CTRCD), and global longitudinal strain is considered useful for anthracycline therapy. Troponin I/T and BNP/NT-proBNP are used as biomarkers of cardiac function. When a patient has reduced LVEF, a cardiologist should be consulted for treatment of CTRCD and cardioprotective therapy should be considered.

Recent advances in molecular genetic research, driven by the development of genomic analysis technologies, have significantly improved treatment outcomes for leukemia. In recent years, mounting evidence indicates that germline genetic background influences drug sensitivity and the risk of adverse effects, underscoring the growing importance of personalized treatment strategies. In particular, the NUDT15 polymorphism, which determines sensitivity to 6-mercaptopurine, has garnered significant attention. Notably, a low-activity variant of this polymorphism, prevalent in Asian countries, has been shown to substantially increase the risk of bone marrow suppression and other adverse effects. Pre-treatment analysis of the NUDT15 polymorphism has demonstrated utility in dose adjustment, helping to mitigate the risk of treatment-related toxicities. Studies have also explored the relationship between genetic background and late complications of leukemia treatment. Optimization of therapeutic strategies based on pharmacogenetic insights holds promise for minimizing complications while maximizing treatment efficacy for each individual patient.

Hepatitis B virus(HBV)reactivation during cancer chemotherapy is a life-threatening condition with a high risk of severe or fulminant disease. Effective management is essential; however, individual physicians may lack a structured system for handling HBV-related risks, and both physicians and pharmacists often face significant administrative burdens, including making inquiries, entering orders for additional testing, and verifying appropriate orders. To address this challenge, we developed a pharmacist-initiated, protocol-based pharmacotherapy management system for HBV(PBPM-HBV), allowing pharmacists to order HBV-related tests on behalf of physicians in accordance with the Guidelines for the Safety Management of Medical Information Systems. Implementing PBPM-HBV under these guidelines reduced the number of HBV-related test requests from 224 to 50, resulting in an approximately 75.7% reduction in workload. The introduction of PBPM-HBV at our hospital has improved workflow efficiency for both physicians and pharmacists while ensuring the safety of the medical information system and cancer chemotherapy processes.