Difference in SARS-CoV-2 Antibody Status Between Patients With Cancer and Health Care Workers During the COVID-19 Pandemic in Japan.

Importance: Patients with cancer and health care workers (HCWs) are at high risk of SARS-CoV-2 infection. Assessing the antibody status of patients with cancer and HCWs can help understand the spread of COVID-19 in cancer care. Objective: To evaluate serum SARS-CoV-2 antibody status in patients with cancer and HCWs during the COVID-19 pandemic in Japan. Design, Setting, and Participants: Participants were enrolled for this prospective cross-sectional study between August 3 and October 30, 2020, from 2 comprehensive cancer centers in the epidemic area around Tokyo, Japan. Patients with cancer aged 16 years or older and employees were enrolled. Participants with suspected COVID-19 infection at the time of enrollment were excluded. Exposures: Cancer of any type and cancer treatment, including chemotherapy, surgery, immune checkpoint inhibitors, radiotherapy, and targeted molecular therapy. Main Outcomes and Measures: Seroprevalence and antibody levels in patients with cancer and HCWs. Seropositivity was defined as positivity to nucleocapsid IgG (N-IgG) and/or spike IgG (S-IgG). Serum levels of SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured by chemiluminescent enzyme immunoassay. Results: A total of 500 patients with cancer (median age, 62.5 years [range, 21-88 years]; 265 men [55.4%]) and 1190 HCWs (median age, 40 years [range, 20-70 years]; 382 men [25.4%]) were enrolled. In patients with cancer, 489 (97.8%) had solid tumors, and 355 (71.0%) had received anticancer treatment within 1 month. Among HCWs, 385 (32.3%) were nurses or assistant nurses, 266 (22.4%) were administrative officers, 197 (16.6%) were researchers, 179 (15.0%) were physicians, 113 (9.5%) were technicians, and 50 (4.2%) were pharmacists. The seroprevalence was 1.0% (95% CI, 0.33%-2.32%) in patients and 0.67% (95% CI, 0.29%-1.32%) in HCWs (P = .48). However, the N-IgG and S-IgG antibody levels were significantly lower in patients than in HCWs (N-IgG: ß, -0.38; 95% CI, -0.55 to -0.21; P < .001; and S-IgG: ß, -0.39; 95% CI, -0.54 to -0.23; P < .001). Additionally, among patients, N-IgG levels were significantly lower in those who received chemotherapy than in those who did not (median N-IgG levels, 0.1 [interquartile range (IQR), 0-0.3] vs 0.1 [IQR, 0-0.4], P = .04). In contrast, N-IgG and S-IgG levels were significantly higher in patients who received immune checkpoint inhibitors than in those who did not (median N-IgG levels: 0.2 [IQR, 0.1-0.5] vs 0.1 [IQR, 0-0.3], P = .02; S-IgG levels: 0.15 [IQR, 0-0.3] vs 0.1[IQR, 0-0.2], P = .02). Conclusions and Relevance: In this cross-sectional study of Japanese patients with cancer and HCWs, the seroprevalence of SARS-CoV-2 antibodies did not differ between the 2 groups; however, findings suggest that comorbid cancer and treatment with systemic therapy, including chemotherapy and immune checkpoint inhibitors, may influence the immune response to SARS-CoV-2.

Reduction in nephrotoxicities using short hydration for chemotherapy containing cisplatin: a consecutive analysis of 467 patients with thoracic malignancies.

BACKGROUND: Conventional hydration (CH) in chemotherapy containing cisplatin (CDDP) has been recommended to prevent renal toxicity. Although an increasing number of studies have demonstrated the feasibility of short hydration (SH), few large studies have reported the superiority of SH, compared with CH, in terms of nephrotoxicities. METHODS: We conducted a consecutive retrospective analysis of 467 patients who had been treated with chemotherapy including CDDP. Statistical analyses were performed to evaluate the risk factors for nephrotoxicities. The following factors were included in the analyses: age, sex, performance status (PS), concomitant thoracic radiotherapy, CDDP dose, magnesium supplementation, baseline creatinine values and method of hydration. RESULTS: The patients' characteristics were as follows: male/female, 323/144 patients; median age (range), 62 (27-69) years; PS 0/1/2/3, 238/217/10/2 patients and SH/CH, 111/356 patients. The proportion of patients requiring a CDDP dose reduction in the SH group was 6.3%, while that in the CH group was 12.9%. Patients who discontinued CDDP because of nephrotoxicities accounted for 0.9% of the patients in the SH group and 2.2% of the patients in the CH group. After CDDP-based chemotherapy, a creatinine increase of more than grade 1 was observed in 14.4% and 33.1% of the patients in the SH and CH groups, respectively. A logistic regression analysis revealed a significantly lower incidence of grade 1 or higher creatinine toxicity after the first cycle of chemotherapy in the SH group (OR, 0.20; 95% CI 0.06 to 0.63; p=0.006). CONCLUSIONS: SH resulted in a significantly lower incidence of nephrotoxicity.

Oral rehydration solution (OS-1) as a substitute of intravenous hydration after cisplatin administration in patients with lung cancer: a prospective multicenter trial.

BACKGROUND: The aim of this trial was to evaluate the safety and efficacy of oral hydration as a substitute for intravenous hydration after cisplatin (CDDP) administration. METHODS: The major eligibility criteria included patients with lung cancer, indications for a CDDP-based regimen at a dose of 60 mg/m2 or higher, an age of between 20 and 74 years and adequate renal function. Antiemetic prophylaxis consisted of an appropriate dose of palonosetron, aprepitant, dexamethasone and magnesium sulfate (8 mEq). Five hundred millilitres of commercially available oral hydration solution (OS-1: Otsuka Pharmaceutical Factory, Tokushima, Japan) was used as a substitute for intravenous posthydration. The planned sample size was 46 to reject a proportion of 70% under an expectation of 88% with a power of 90% and an alpha error of 5%. RESULTS: Between May and November 2013, 31 men and 15 women with a median (range) age of 65 (33-74) years were enrolled from three institutions. Of these, five received adjuvant chemotherapy, 17 received definitive chemoradiotherapy and 24 received chemotherapy for advanced diseases. The median (range) number of chemotherapy cycles was 4 (1-5). After the first cycle of CDDP administration, none of the patients experienced a creatinine elevation of grade 2 or higher, thereby meeting the primary endpoint. Of the 46 patients, 45 (97.8%, 95% CI 88.2 to 99.9) completed the CDDP-based chemotherapy without grade 2 or higher renal dysfunction. CONCLUSION: Oral hydration can be used as a safe and convenient substitute for intravenous posthydration for CDDP administration at the standard dose. TRIAL REGISTRATION NUMBER: UMIN000010201.

Protective effect of magnesium preloading on cisplatin-induced nephrotoxicity: a retrospective study.

OBJECTIVE: Magnesium supplementation has been reported to have a nephroprotective effect on cisplatin-induced renal dysfunction, but little evidence exists regarding the effect of magnesium preloading before cisplatin administration. We started to include magnesium preloading (8 mEq) in cisplatin-containing treatment regimens in January 2011. The aim of the present study was to evaluate whether magnesium preloading reduces cisplatin-induced nephrotoxicity. METHODS: We retrospectively reviewed 496 thoracic malignancy patients treated with cisplatin (≥60 mg/m²)-containing regimens as a first-time chemotherapy between January 2009 and December 2011. We compared the incidence of Grade ≥2 serum creatinine elevation according to the Common Terminology Criteria for Adverse Events, version 4.0, between magnesium preloading group (n = 161 [32%]) and non-magnesium preloading group (n = 335 [68%]) during the first cycle and all cycles. RESULTS: The median number of administered cycles was four in both groups. The incidence of Grade ≥2 serum creatinine elevation in magnesium preloading group was significantly lower during both the first cycle and all cycles than in the non-magnesium preloading group (4.9 versus 19.1% during the first cycle, and 14.2 versus 39.7% during all the cycles). A multivariate analysis indicated that magnesium preloading significantly reduced cisplatin-induced nephrotoxicity throughout the entire period from after the first administration (odds ratio: 0.262, 95% confidence interval: 0.106-0.596 during the first cycle, and odds ratio: 0.234, 95% confidence interval: 0.129-0.414 during all cycles). CONCLUSIONS: Magnesium preloading before cisplatin administration significantly reduced cisplatin-induced nephrotoxicity.

Lung cancer working group report.

Asia needs a guideline for non-small-cell lung cancer because of differences in medical care, medical care insurance, ethnic variation and drug approval lag within Asian countries and compared with Western countries. Due to ethnic differences, drug dosages are often higher in the USA than in Japan. EGFR mutation in non-small-cell lung cancer was detected in 32% of Asians but only 6% of non-Asians, while differences in irinotecan metabolism cause higher frequencies of toxicity (leukopenia, diarrhea) in Asians. Pharmacodynamic ethnic differences in relation to paclitaxel/carboplatin resulted in longer median survival and a higher 1-year survival rate for Japanese-advanced non-small-cell lung cancer patients compared with Americans. To solve the problem of drug lag, pharmaceutical companies must perform multinational Asian clinical trials with quick accrual of patients, while regulatory authorities must establish high-quality, efficient approval processes, and achieve regulatory harmonization. The National Comprehensive Cancer Network promotes creation of national clinical practice guidelines, and Korea, China and Thailand adapted the National Comprehensive Cancer Network guidelines. Many Asian countries still lack such guidelines, and there are no pan-Asian guidelines for non-small-cell lung cancer. Japan developed its own non-small-cell lung cancer guidelines and also a gefitinib guidance. The study group members concluded that immediate establishment of an Asian non-small-cell lung cancer guideline will be difficult because of the differences among the countries. Asian collaborative trials on treatment of non-small-cell lung cancer need to be started at an early date to generate Asian data.

Efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B12 in previously treated patients with non-small cell lung cancer.

PURPOSE: The objective of this study was to evaluate the efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B(12) in pretreated Japanese patients with advanced non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Patients with an Eastern Cooperative Oncology Group performance status 0 to 2, stage III or IV, and who received previously one or two chemotherapy regimens were randomized to receive 500 mg/m(2) pemetrexed (P500) or 1,000 mg/m(2) pemetrexed (P1000) on day 1 every 3 weeks. The primary endpoint was response rate. RESULTS: Of the 216 patients evaluable for efficacy (108 in each arm), response rates were 18.5% (90% confidence interval, 12.6-25.8%) and 14.8% (90% confidence interval, 9.5-21.6%), median survival times were 16.0 and 12.6 months, 1-year survival rates were 59.2% and 53.7%, and median progression-free survival were 3.0 and 2.5 months for the P500 and P1000, respectively. Cox multiple regression analysis indicated that pemetrexed dose was not a significant prognostic factor. Drug-related toxicity was generally tolerable for both doses; however, the safety profile of P500 showed generally milder toxicity. Main adverse drug reactions of severity grade 3 or 4 were neutrophil count decreased (20.2%) and alanine aminotransferase (glutamine pyruvic transaminase) increased (15.8%) in P500 and neutrophil count decreased (24.3%), WBC count decreased (20.7%), and lymphocyte count decreased (18.0%) in P1000. One drug-related death from interstitial lung disease occurred in the P500. CONCLUSION: P500 and P1000 are similarly active with promising efficacy and acceptable safety outcomes in pretreated patients with NSCLC. These results support the use of P500 as a second- and third-line treatment of NSCLC.