Japanese Journal of Cancer and Chemotherapy最新文献

Antibody-drug conjugate(ADC)contain monoclonal antibodies that target-specific tumor antigens, cytotoxic payloads, and linkers. ADCs use antibodies to selectively act on tumors, making them more effective and less toxic. In Japan, 4 drugs are approved as ADCs for leukemia and lymphoma: gemtuzumab ozogamicin(GO)consists of an anti-CD33 monoclonal antibody bound to calicheamicin via a linker, approved for relapsed/refractory acute myeloid leukemia. Brentuximab vedotin (BV)has anti-CD30 antibodies bound to MMAE via a linker and is approved for CD30-positive Hodgkin's lymphoma, peripheral T-cell lymphoma, and cutaneous T-cell lymphoma. BV, in combination with multi-agent chemotherapy, resulted in significantly prolonged progression-free survival(PFS)in classical Hodgkin's lymphoma and peripheral T-cell lymphoma compared to the control group. Inotuzumab ozogamicin(IO)has an anti-CD22 antibody bound to calicheamicin via a linker, approved for relapsed/refractory CD22-positive B-cell acute lymphoblastic leukemia. In relapsed/refractory B-cell acute lymphoblastic leukemia, IO showed a higher complete remission rate than the control group. Polatuzumab vedotin(PV)has an anti-CD79b monoclonal antibody bounds to MMAE via a linker, approved for diffuse large B-cell lymphoma(DLBCL). In DLBCL patients with an international prognostic index score(IPI score)of 2 or higher, the combination of PV plus rituximab, cyclophosphamide, doxorubicin, and prednisone(PV+R-CHP)extended PFS at 2 years compared with R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), which has long been the standard of care. As shown, ADCs exhibit high therapeutic efficacy in leukemia and lymphoma treatment, but many aspects of their resistance mechanisms remain unclear and require further research.

In May 2022, Hyogo Medical University Hospital introduced protocol-based pharmacotherapy management(PBPM), which is jointly planned by doctors and pharmacists, for certain cancer drug therapies. Colorectal cancer patients who underwent outpatient cancer chemotherapy in the Department of Lower Gastrointestinal Surgery from October to December 2021(before the introduction of PBPM)and from May to August 2022(after the introduction of PBPM)were retrospectively studied. The proportion of clinical examinations performed, number of prescription questions, and time taken by pharmacists to solve the prescription questions before and after the introduction of PBPM were compared. Additionally, the number of modifications made in the medical record by pharmacists on behalf of doctors in response to the prescription questions was assessed. The proportion of clinical examinations performed(clinical examinations actually performed/clinical examinations that should have been performed)improved from 93.2%(260/279)before to 98.8%(405/410)after the introduction of PBPM(p<0.001). The number of prescription questions decreased from an average of 64.7(±11.9)per month before to an average of 29.5(±3.4)per month after the introduction of PBPM. The average number of modifications made in the medical record by pharmacists on behalf of the doctors in response to the prescription questions was 25.8(±5.4)per month after the introduction of PBPM. There was no significant difference before and after the introduction of PBPM in regard to the median(interquartile range)time taken by pharmacists to solve the prescription questions (before PBPM: 1.88 minutes per case[1.70-2.28 minutes]; after PBPM: 1.71 minutes per case[1.61-2.06 minutes][p= 0.75]). The increased proportion of clinical examinations performed after the implementation of PBPM may have improved the safety of cancer drug management, and the decreased number of prescription questions is speculated to have led to a reduction in physician workload.

The efficacy of antibody-drug conjugates(ADCs)has been well-established in clinical use, prompting ongoing research and development efforts to advance the field of ADCs further. This chapter provides overview of the structure and mechanism of action of ADCs, detailing the roles of its components: the antibody, the payload, and the linker. ADCs leak from cancer vessels to bind to specific antigens on the surface of tumor cells. Upon binding and internalization, the drug is released by metabolic enzymes, such as peptidases in the lysosome. The therapeutic window of the conjugated drug is therefore expanded. To enhance the efficacy of ADCs, the chapter will also explore the development of methodologies for generating homogeneous ADCs and the concept of bystander effects, which are particularly relevant in the tumor microenvironment. Additionally, innovative approaches such as radioimmunotherapy, utilizing alpha-ray emitting radionuclides, and photoimmunotherapy, are discussed as promising next-generation ADC strategies. The integration of ADCs with immunotherapy may offer amplified effectiveness through synergistic actions. The chapter underscores that the prolonged therapeutic impact of ADCs cannot be solely attributed to the targeted delivery and controlled release of the payload. A comprehensive understanding from the perspective of cancer immunology is imperative for elucidating the underlying mechanisms contributing to their sustained efficacy.

Antibody-drug conjugates(ADCs)have become widely used in the treatment of various malignancies over the past 15 years. In breast cancer, T-DM1 and T-DXd which is HER2-targeted ADC have been approved and are broadly used in Japan. Sacituzumab govitecan, TROP2-ADC has been approved in US. Hence, multiple ADCs could be used for breast cancer treatment. In gynecological cancers, tisotumab vedotin for cervical cancer and mirvetuximab soravtansine for ovarian cancer have been approved in the US. Optimizing treatment sequences and overcoming resistance mechanisms for ADC are important challenges in the situations where multiple ADCs are available. The current development landscape suggests further enhancement of ADC treatment efficacy through new targets, novel payloads, bispecific ADCs, and combination therapies with immunotherapy. This article outlines the current status of ADCs in breast and gynecological cancers, highlighting ongoing development and challenges emerging in the field.

Undifferentiated sarcoma of the liver is rare, especially in adults, and is an aggressive malignancy that originates from the primary mesenchymal tissues. A 53-year-old man was referred to our hospital for further evaluation of a low-grade fever. Contrast-enhanced CT revealed an 18-cm tumor in the right lobe of the liver. The tumor was characterized by low-density areas suspected of cystic components, a high-density area suspected of hemorrhage, and contrast enhancement in the thickened marginal and internal septa. MRI revealed a high-intensity tumor with a heterogeneous structure on T2-weighted images. Angiosarcoma of the liver with intratumoral hemorrhage was suspected, and right hepatectomy was performed. The pathological diagnosis was an undifferentiated sarcoma based on the presence of undifferentiated mesenchymal tumor cells with a stellate to spindle-shaped pleomorphism. Following a multidisciplinary discussion, 4 courses of the AI regimen (doxorubicin and ifosfamide)were administered as adjuvant chemotherapy, and no recurrence was confirmed at 2 years and 6 months follow-up. Our case suggests that radical resection followed by adjuvant chemotherapy may contribute to a favorable prognosis for undifferentiated sarcoma of the liver.

Adenomyoepithelioma(AME)of the breast is a rare condition, and comorbidity with carcinoma is even more unusual. Herein, we report a case of both AME and apocrine carcinoma in different breasts of a single patient. A 48-year-old woman presented to our clinic with a right breast tumor. Fine needle aspiration cytology(FNAC)was indeterminate and suspicious for both papilloma and non-invasive ductal carcinoma, but excisional biopsy indicated an AME. Immuno-histochemical staining showed EMA(+), AE1/3(+), and CK7(+)mammary duct cells and αSMA(+), CK5/6(+), and p63(+) myoepithelial cells. Six months later, the patient noticed a left breast tumor, and although FNAC indicated no malignancy, after 6 additional months, the tumor size had increased and a mammography revealed tumor microcalcification, suggesting malignancy. Vacuum-assisted biopsy revealed an apocrine carcinoma. The patient underwent partial mastectomy and sentinel node biopsy, followed by radiotherapy and chemotherapy. The post-surgical pathology was pT1pN0M0, Stage Ⅰ, triple- negative, and the patient was disease-free for 12 years postoperatively. To our knowledge, this is only the second case of AME and breast cancer in different breasts reported in Japan.

Background: Cancer patients are often complicated by weight loss and malnutrition, thus it is important to provide nutritional therapy in parallel with disease treatment. This study examined the significance of early intervention by NST for cancer patients.

Methods: Seventy-five cancer patients out of 281 patients who underwent NST intervention between July 2021 and June 2022 were included. Intervention outcomes, such as energy and protein sufficiency(=intake/target), and final evaluation by a NST nutritionist at the end of the intervention("improvement"/"unchanged"/"disease progression"/ "death"), were compared between patients who received NST intervention within 7 days from admission(Group A)and after 7 days from admission(Group B).

Results: Nutritional sufficiency at the end of NST intervention was higher in Group A for both energy and protein, and the proportion of"improvement"was higher in Group A for the final evaluation by a NST nutritionist. Patients' situation(pre-initial treatment/post-chemotherapy/post-surgery/worsening nutritional status during follow-up)was biased between 2 groups, however Group A showed better results for nutritional sufficiency rate and final evaluation in each subgroup of patients' situation.

Conclusion: Early intervention may improve the effectiveness of NST for cancer patients. It is important to extract subjects and start NST intervention at early timing.

The G-Lasta BodyPod(BodyPod), a newly developed on-body injector that automatically injects pegfilgrastim(Peg-G), has been approved for clinical use in Japan. However, its precise operation is yet to be established. Exploring accumulated literature, we reviewed the efficacy and safety of the Peg-G on-body injector used in other countries and determined its eligibility criteria, operating procedures, and troubleshooting guideline. Overseas, the Peg-G on-body injectors were utilized in relatively young patients, approximately 50 years of age. The incidence of on-body injector failure was low(0.1-4.9%)and comprised injection failure, drug leakage, and dropout. We defined eligible patients as those capable of self-management (handling the BodyPod and understanding troubleshooting). For convenience of patients, the BodyPod was applied to them in the outpatient chemotherapy center by nurses with expertise in the application technique. We categorized BodyPod- related issues as(1)allergic symptoms after application and Peg-G injection,( 2)malfunction or failure before initiating the Peg-G injection, or(3)malfunction or failure after initiating the Peg-G injection. In conclusion, a careful understanding of the handling and malfunction of the BodyPod is essential prior to application in clinical settings, along with patient indications and troubleshooting guidelines appropriate for each hospital.

The gut(intestinal)microbiota is said to number about 1,000 species and about 100 trillion, and recent studies have reported that there is an interaction between cancer and the gut microbiota. It has been elucidated that certain gut microbiota affects the occurrence and risk of cancer, and in gastric cancer, an association with Helicobacter Pylori infection has been reported. Studies on multiple cancer types have also reported a correlation between the gut microbiome and the efficacy and toxicity of cancer immunotherapy. The gut microbiome has attracted attention as a promising biomarker for predicting the efficacy of immunotherapy, and interventional trials have been conducted to verify that it increases the efficacy of immunotherapy. Biomarker studies of immunotherapy and gut microbiome in advanced gastric cancer have reported associations between gastric cancer-specific gut microbiota and therapeutic efficacy and toxicity.

At Oita University Hospital, we switched our usage of pemetrexed(PEM)from brand-name to generic drugs. We conducted a comparative study of the preparation efficiency and therapeutic safety with the brand-name product and examined the economic effect thereof. The incidence of adverse drug reactions was investigated retrospectively using electronic medical records for patients who received PEM brand-name and generic drugs at our hospital between April 2021 and December 2022. The preparation time per mg was significantly shorter in the generic group at 0.17(0.08-0.38)seconds compared to 0.34(0.15-0.94)seconds for the brand-name group(p<0.01). Regarding the safety comparison, none of the 13 eligible patients developed new hematologic or non-hematologic toxicities of Grade 2 or higher after switching to the generic product. The switch to generics had an economic impact of 7,369,278 yen during the study period. The results suggest that switching from brand-name to generic products is reasonable from the perspectives of therapeutic safety and economic benefits, as well as the expected improvement in preparation efficiency.