Japanese journal of clinical oncology最新文献

Background: In systemic treatment for renal cell carcinoma, some patients require dose reduction to prevent adverse events. However, there is currently almost no evidence to support a reduced starting dose for cabozantinib + nivolumab (C + N) in clinical practice.

Methods: We retrospectively analyzed single-institution data for patients with renal cell carcinoma with an assessed response to C + N. The starting dose was determined during a multidisciplinary meeting for each patient by considering the following patient characteristics: age, performance status, body weight, and medical history. In all cases, the dosage and schedule of nivolumab could not be modified. Efficacy and adverse events were examined.

Results: Fourteen and eighteen patients, respectively, received 20 (reduced dose) and 40 mg (standard dose) of cabozantinib in C + N treatment. The median age was 79.5 years in the reduced-dose group and 69.5 years in the normal-dose group (P < .0001). The objective response rate was 71% in the reduced-dose group and 78% in the normal-dose group (P = .6807). There were no significant differences in progression-free survival and overall survival, nor in the overall and grade ≥ 3 adverse events rates between the groups. Liver dysfunction of any grade occurred significantly more frequently in the normal-dose group (61%) versus the reduced-dose group (21%) (P = .0247).

Conclusions: A 20-mg starting dose of cabozantinib in C + N therapy can achieve almost the same efficacy as a normal starting dose for patients who are hesitant to start treatment at the normal 40-mg dose.

Background: Multiple myeloma is a significant cause of mortality, and treatments for patients with relapsed/refractory multiple myeloma have limited efficacy. Treatment regimens with belantamab mafodotin have demonstrated significant improvement in progression-free survival compared with current standard-of-care regimens but have been associated with an increased risk of ocular adverse events (OAEs). These practice guidelines aim to provide recommendations to support Japanese clinicians in managing OAEs and facilitate confidence in the use of belantamab mafodotin.

Methods: An expert panel of Japanese haematologists/oncologists and ophthalmologists convened to discuss and agree on the recommendations for managing OAEs in patients treated with belantamab mafodotin.

Results: The expert panel identified four key themes and 13 clinical questions to guide the recommendations for managing belantamab mafodotin-related OAEs in the real-world setting in Japan. The four key themes were: (i) identification of OAEs associated with belantamab mafodotin treatment; (ii) management and dose modification of belantamab mafodotin treatment for OAEs; (iii) multidisciplinary collaboration for effective management of ocular events; and (iv) a patient-centred approach to the management of OAEs.

Conclusions: The recommendations in these practice guidelines build on published clinical trial evidence and the practical experience of the expert panel to help Japanese clinicians make informed treatment decisions in the management of multiple myeloma in the real-world setting.

Currently, it is routine to determine the treatment plans for pancreatic ductal adenocarcinoma (PDAC) based on the resectability status, which is classified into: resectable (R), borderline resectable (BR), and unresectable (UR). In patients with R-PDAC, we have frequently encountered distant metastases only after laparotomy. In addition, early postoperative recurrence may be noted even after curative resection. To overcome these issues, preoperative treatment has been recommended to estimate the tumor aggressiveness and avoid unnecessary surgery. For BR disease, all clinical trials comparing upfront surgery with preoperative treatment have shown a better prognosis with the latter. For UR disease, especially with distant metastases, a previous multi-institutional retrospective study suggested that we should consider conversion surgery after at least 8 months of chemotherapy. However, the postoperative prognosis remains unsatisfactory. Appropriate regimens and durations of preoperative treatment for each respectability status have yet to be established. Other issues, such as the feasibility of arterial reconstruction and whether all metastatic lesions should be removed, remain to be addressed.

Objectives: Treatment delay can adversely affect cancer prognosis and public health. However, previous studies have not examined the association between cancer treatment delay and 5-year mortality risk for various cancer types in a single study population.

Methods: We used retrospective cohort data from 21 740 patients diagnosed with common cancers between 2000 and 2017, with mortality follow-up to 2022, from the Philippines' Department of Health-Rizal Cancer Registry to understand how treatment delay of <30, 30-90, or >90 days was associated with 5-year all-cause mortality risk, by cancer type and stage at diagnosis. Poisson regression with robust variance was used to obtain the risk ratio and 95% confidence interval for the associations.

Results: After adjusting for confounding, patients with treatment delays of more than 90 days had significantly higher 5-year mortality risk (risk ratio = 1.09; 95% confidence interval: 1.04-1.14) compared to those with delays of <30 days. Treatment delay was significantly associated with higher 5-year mortality in breast and cervical cancers, but not for the other cancer types (P-trend < .05). There was also a significant association between treatment delay and 5-year mortality of non-metastatic but not metastatic cancer at diagnosis (P-trend < .05).

Conclusion: Our findings suggest that the 5-year prognosis of certain cancer types and non-metastatic cancer may be more adversely influenced by their delayed treatment, which will inform cancer control programs globally to reduce treatment delay and improve cancer prognosis.

Background: Despite several attempts to improve the prognosis of patients with diffuse large B-cell lymphoma (DLBCL), the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen remains the standard of care in previously untreated DLBCL. A randomized phase II/III study (JCOG0601) was performed to investigate the efficacy of dose-dense weekly rituximab combined with standard CHOP (RW-CHOP). Herein, we report the final results of JCOG0601 as a post hoc assessment after an 8-year follow-up.

Methods: Patients aged 20-79 years with previously untreated DLBCL (stages I-IV, performance status 0-2) were randomized to either standard R-CHOP or RW-CHOP.

Results: Between December 2007 and December 2014, 421 patients were randomly assigned to R-CHOP (n = 213) or RW-CHOP (n = 208). With a median follow-up of 9.6 years, no meaningful differences were found in progression-free survival (PFS) and overall survival (OS) [hazard ratio (HR) in PFS, 0.94; 95% confidence interval (CI), 0.67-1.32; HR in OS, 0.94; 95% CI, 0.63-1.41]. The median PFS and OS were not estimable in both arms. Twenty-one (5.0%) cases of grade ≥ 3 cardiac toxicity were observed. The cumulative incidence rates of secondary malignancy were 14.6% and 16.8% in the R-CHOP and RW-CHOP arms, respectively. The median time from study enrollment to the onset of secondary malignancy was 4.5 years, and the incidence was time-dependent. No unexpected adverse events, including opportunistic infections, occurred.

Conclusion: These final follow-up data confirmed the nonsuperiority of RW-CHOP in terms of PFS and OS. Standard R-CHOP remains the standard of care for untreated DLBCL.

Background: Opioids are essential for cancer pain; however, regional and hospital prescribing variations in Japan remain poorly understood. This study aimed to investigate the regional and hospital functional differences in opioid prescribing among terminally ill patients with cancer in Japan using nationwide claims data.

Methods: We analysed anonymized claims data from the DeSC database, focusing on patients who died of cancer in hospitals (2018-2022). We calculated opioid prescription prevalence and mean daily doses (converted to oral morphine equivalents) in the last 30 days of life. Outcomes were compared across regions and hospital functions using multivariate logistic and linear regression models adjusted for age, sex, and cancer type.

Results: We analysed 119 850 decedents. Oxycodone injection use was highest in Tokai (16.4%) and South Kanto (15.7%), approximately four times that in Shikoku (4.0%). Transdermal fentanyl use ranged from 51.5% in Kyushu/Okinawa to 25.4% in South Kanto. Oxycodone injections increased with hospital functionality (4.1% in non-acute care vs. 20.4% in university hospitals), whereas transdermal fentanyl use declined (56.7%-13.1%). Compared to South Kanto, adjusted odds ratios (ORs) for opioid prescribing were higher in Kyushu/Okinawa (1.29) and lower in Kinki (0.68). For dose, no region exceeded South Kanto, and the lowest geometric mean ratio (GMR) was observed in Shikoku (0.87). No significant differences in adjusted ORs or GMRs were observed across hospital categories.

Conclusion: Opioid prescribing patterns varied across regions and hospital functions, with significant differences in both prevalence and dosing. These findings may contribute to advancing the uniform implementation of palliative care.

Background: Immune checkpoint inhibitors (ICI) have recently been developed and launched in Japan, at the same time, soaring national healthcare costs have become one of the major social issues. We investigated the volume of prescriptions and the drug costs of ICIs using National Database (NDB) open data.

Methods: This is a retrospective cohort study; we used aggregate data between fiscal year (FY)2015 and FY2022 (April 2015-March 2023) from the NDB. The drugs of interest included nivolumab, ipilimumab, pembrolizumab, avelumab, atezolizumab, and durvalumab. Findings are presented as descriptive statistics.

Results: Since the introduction of ICIs, prescription volume of all ICIs increased overtime. Overall ICI drug costs increased from 16 898 million yen in FY2015 to 419 615 million yen in FY2022; the total of ICI drug costs from FY2015 to FY2022 was over 1 793 billion yen. For each drug, >70% of drug costs were generally for patients aged 65 years or older. In addition, total drug costs tended to increase over the years among those aged 75 and over.

Conclusions: Drug costs for ICIs are significantly increasing despite the Japanese government's frequent efforts to reduce ICI drug prices. The elderly population made up a particularly high proportion of those burdened with the higher costs. Healthcare economic policies are warranted to ensure efficient distribution of budgetary resources.