Glucocorticoid-related adverse events in ethnic Chinese patients

IntroductionThe treatment of relapsed/refractory multiple myeloma (RRMM), a common hematological malignancy, remains a great challenge in China, partially due to the limited accessibility to novel agents and inadequate public health insurance coverage. Ixazomib, a novel oral proteasome inhibitor (PI), was approved by the China Food and Drug Administration (CFDA) for RRMM in 2018. While bortezomib, a traditional PI, is the recommended agent in the clinical guideline for MM. Here, we compared their costs and effectiveness.MethodsRRMM patients who has received an ixazomib-based regimen (at least 2 cycles) were analyzed. Using a propensity score matching method, we generated a control group of RRMM patients who received the bortezomib-based regimen. The criteria included the number of treatment lines, age, and the revised international staging system stage (R-ISS) which representing the disease stage for myeloma, and paired at a ratio of 1:2 (allowing one control to match multiples). The difference in hospitalization stay, grade 3/4 adverse events rates, overall response rate (ORR), mortality during treatment, and treatment costs was then compared.ResultsNineteen patients received ixazomib and twenty-seven that received bortezomib were included. The ixazomib-group demonstrated a shorter hospital stay (9 days versus 27 days, p < 0.001), lower grade 3–4 adverse events rates (42.1% versus 55.6%, p < 0.001), higher ORR (63.2% versus 48.1%, p = 0.228), and lower mortality rate during treatment (0% versus 7.4%, p = 0.169) than that of bortezomib-group. The ixazomib group had lower total costs (127,620CNY versus 156,424CNY [18,033USD versus 22,103USD], p > 0.05), lower drug costs (98,376CNY versus 103,307CNY [13,901USD versus 14,598USD], p > 0.05), and the lower costs of supportive treatment (5,507CNY versus 14,701 CNY [778USD versus 2,077USD], p < 0.001). Only in terms of self-funded costs, the bortezomib-based regimen was significantly lower (37,127CNY versus 11,521CNY [5,246USD versus 1,628USD], p < 0.001).ConclusionsCompared with the bortezomib-based regimen, the ixazomib-based regimen has better therapeutic effects on MM patients while saving costs. Hence, it may be preferable for use in the treatment of RRMM in China.

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Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety

Infectious Diseases of Poverty ◽

10.1186/s40249-021-00819-2 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Jing-Tao Gao ◽

Juan Du ◽

Gui-Hui Wu ◽

Yi Pei ◽

Meng-Qiu Gao ◽

...

Keyword(s):

Adverse Events ◽

Multidrug Resistant ◽

World Health ◽

Chinese Patients ◽

Prolonged Treatment ◽

Drug Resistant ◽

Aminosalicylic Acid ◽

Clinical Patient ◽

New Drug ◽

Resistant Tuberculosis

Abstract Background World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). Methods AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. Results By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1–2) and 33.1% as serious (Grade 3–5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75–169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. Conclusions Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

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Basal Cell Carcinoma of the Head and Neck Region in Ethnic Chinese

International Journal of Surgical Oncology ◽

10.1155/2011/890908 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Velda Ling Yu Chow ◽

Jimmy Yu Wai Chan ◽

Richie Chiu Lung Chan ◽

Joseph Hon Ping Chung ◽

William Ignace Wei

Keyword(s):

Neck Region ◽

Surgical Excision ◽

Chinese Patients ◽

Skin Closure ◽

Recurrence Rates ◽

Tumour Control ◽

Female Patients ◽

Ethnic Chinese ◽

Elderly Female ◽

Tertiary Centre

Objectives.This study aims to report our experience in the management of HNBCC in ethnic Chinese over a 10-year period.Methods.A retrospective review of all ethnic Chinese patients with HNBCC treated in a tertiary centre from 1999 to 2009.Results.From 1999 to 2009, 225 patients underwent surgical excision for HNBCC. Majority were elderly female patients. Commonest presentation was a pigmented (76.2%) ulcer (64.8%) over the nose (31.6%). Median skin margin taken on tumour excision was 2.0 mm; primary skin closure was achieved in 51.8%. Postresection skin margin was clear in 75.4%. Of those with inadequate skin margins, 56.7% opted for further treatment, 43.4% for observation. Recurrence rates were 2.6% and 13.8%, respectively (). Overall recurrence rate was 5.5%.Conclusions.HNBCC commonly presented as pigmented ulcers over the nose of elderly female patients in our locality. Adequate tumour excision ± reconstruction offered the best chance of cure. Reexcision of those with inadequate skin margins improved local tumour control.

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Dealing With Death Taboo: Discussion of Do-Not-Resuscitate Directives With Chinese Patients With Noncancer Life-Limiting Illnesses

American Journal of Hospice and Palliative Medicine® ◽

10.1177/1049909119828116 ◽

2019 ◽

Vol 36 (9) ◽

pp. 760-766 ◽

Cited By ~ 9

Author(s):

Hon-Wai Benjamin Cheng ◽

Pui-Shan Karen Shek ◽

Ching-Wah Man ◽

Oi-Man Chan ◽

Chun-Hung Chan ◽

...

Keyword(s):

Decision Making ◽

Chinese Culture ◽

Ethnic Disparities ◽

Retrospective Chart Review ◽

Female Gender ◽

Tertiary Hospital ◽

Chinese Patients ◽

Team Approach ◽

Do Not Resuscitate ◽

Ethnic Chinese

Background: Noncancer patients with life-limiting diseases often receive more intensive level of care in their final days of life, with more cardiopulmonary resuscitation performed and less do-not-resuscitate (DNR) orders in place. Nevertheless, death is still often a taboo across Chinese culture, and ethnic disparities could negatively affect DNR directives completion rates. Objectives: We aim to explore whether Chinese noncancer patients are willing to sign their own DNR directives in a palliative specialist clinic, under a multidisciplinary team approach Design: Retrospective chart review of all noncancer patients with life-limiting diseases referred to palliative specialist clinic at a tertiary hospital in Hong Kong over a 4-year period. Results: Over the study period, a total of 566 noncancer patients were seen, 119 of them completed their own DNR directives. Patients had a mean age of 74.9. Top 3 diagnoses were chronic renal failure (37%), congestive heart failure (16%), and motor neuron disease (11%). Forty-two percent of patients signed their DNR directives at first clinic attendance. Most Chinese patients (76.5%) invited family caregivers at DNR decision-making, especially for female gender (84.4% vs 69.1%; P = .047) and older (age >75) age group (86.2% vs 66.7%; P = .012). Of the 40 deceased patients, median time from signed directives to death was 5 months. Vast majority (95%) had their DNR directives being honored. Conclusion: Health-care workers should be sensitive toward the cultural influence during advance care planning. Role of family for ethnic Chinese remains crucial and professionals should respect this family oriented decision-making.

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Pharmacokinetics of Indinavir at 800, 600, and 400 Milligrams Administered with Ritonavir at 100 Milligrams and Efavirenz in Ethnic Chinese Patients Infected with Human Immunodeficiency Virus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.11.4476-4478.2004 ◽

2004 ◽

Vol 48 (11) ◽

pp. 4476-4478 ◽

Cited By ~ 1

Author(s):

Lawrence S. Lee ◽

Anushia Panchalingam ◽

Marline C. Yap ◽

Nicholas I. Paton

Keyword(s):

Human Immunodeficiency Virus ◽

Chinese Patients ◽

Ethnic Chinese ◽

Immunodeficiency Virus ◽

Trough Concentrations ◽

Different Doses

ABSTRACT We assessed the pharmacokinetics of three different doses of indinavir in five patients. All doses achieved trough concentrations above efficacy thresholds. Toxic trough concentrations were observed in all patients receiving 800 mg, in two patients receiving 600 mg, and in none receiving 400 mg. Indinavir at 400 mg may be efficacious and less toxic in patients taking ritonavir and efavirenz.

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Bortezomib (Velcade ™) Observational Study in China: Efficacy and Safety of Bortezomib-Based Regimen in 395 Relapsed or Refractory Multiple Myeloma Patients

Blood ◽

10.1182/blood.v112.11.5179.5179 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5179-5179

Author(s):

Zhi-Xiang Shen ◽

Hua Yan ◽

Linna Wang

Keyword(s):

Multiple Myeloma ◽

Adverse Events ◽

Observational Study ◽

Response Rate ◽

Complete Response ◽

Chinese Patients ◽

Efficacy And Safety ◽

Female Ratio ◽

Bortezomib Treatment ◽

Grade 3

Abstract Introduction: Multiple myeloma (MM) is a plasma-cell malignancy and overall survival for patients who have relapsed after initial therapy is approximately 2 years. Bortezomib (VELCADE TM) is a first-in-class proteasome inhibitor that has demonstrated significant anti-tumor activity in MM patients. Here we report the results of an observational study of the efficacy and safety of bortezomib-based regimens in Chinese relapsed/refractory MM patients. Methods: This was a multi-center, open-label, phase IV observational study designed to enroll 550 patients with relapsed or refractory MM. From Mar 2006 to May 2008, 500 patients with relapsed or refractory MM were enrolled from 43 medical centers in China and 395 of them were evaluated. Bortezomib (0.7 to 1.6 mg/m2 i.v.) was given on days 1, 4, 8, and 11 in in a 21-day cycle, up to a maximum of 8 cycles, combined with other agents, mainly with the addition of dexamethasone (60.1%). Major endpoint included response rate, safety and time to response. Responses of 62% patients were determined by European Group for Blood and Marrow Transplantation criteria (EBMT). Bortezomib withheld if patients developed neutropenia fever, grade 4 haematologic adverse events (AEs), or grade 3 non-haematologic AEs, and re-administered at 75% of the initial dosage after recovery. Results: In 395 evaluable cases, the median age was 59 years (range 35–82) and the male/female ratio was 1.5:1. 90% of patients were in late stage(stage II/III) and 50% of them were IgG subtype. Patients had received various prior therapies before bortezomib treatment, including VAD (31.3%), VBMCP (M2, 15.1%) and thalidomide-based regimens(14.9%), with best response rate of 10.4% complete response (CR) and 42.3% partial response (PR) from prior therapies. 311 (82%) cases of patients received 1.0–1.4mg/m2 bortezomib-based regimens treatment and 38.5% of them received at least 4 cycles of treatment. 364 patients were evaluable for response, the overall response rate was 287/364 (78.8%), 89 patients (24.5%) achieved a CR, 30(8.24%) had a nearly complete response (nCR), 168 (46.2%) had a PR, 39 (10.7%) had minimal response (MR), 24 (6.6%) had stable disease (SD), and the other 14 (3.9%) had progressive disease (PD). Median time to response was 1 cycle of treatment (range 1–6). Patients who received 4 or more cycles of bortezomib treatment achieved a higher response rate (CR+PR: 81.5%) compared to those who received fewer cycles (partly due to adverse events). And prognosis-related analysis showed that the dosage of bortezomib at 1.0 mg/m2 or more had a significant influence on the time to response and response rate, but no obvious effect on response duration, time to progress or the survival time. Drug related adverse events (AEs) were reported in 50.4% of patients during treatment, including hematologic AEs (mainly thrombocytopenia, 22.5%), gastrointestinal AEs (24.8%), and peripheral neuropathy (22.5%). The rates of grade 3–4 AEs of them were 46.1%, 11.2% and 15.7%, respectively. Serious AEs occurred in 33 (8.4%) cases and 23 (70%) patients recovered finally. Most AEs were predictable and manageable. Conclusion: Bortezomib-based regimen is effective treatment with higher response rate and is well tolerated in most Chinese patients with relapsed and refractory MM patients. Long-term follow-up is continuing.

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Capecitabine (X) plus vinorelbine (N) as second-line therapy in Chinese patients (pts) with metastastic breast cancer (MBC)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10679 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10679-10679

Author(s):

B. Xu ◽

L. Tian ◽

Q. Wu ◽

M. Zhou ◽

H. Wang ◽

...

Keyword(s):

Breast Cancer ◽

Adverse Events ◽

Chinese Women ◽

Complete Response ◽

Hepatic Function ◽

Chinese Patients ◽

Thoracic Wall ◽

Large Cities ◽

Grade 3 ◽

Few Data

10679 Background: Breast cancer is one of the most common malignancies among Chinese women and the incidence continues to rise, particularly in large cities such as Shanghai. X monotherapy is consistently effective and very well tolerated in pretreated MBC. N is also commonly used in this indication. In several studies, the combination of X + N led to response rates ranging from 43–67% in first-line MBC. As there are few data on this combination in pretreated MBC, we evaluated the efficacy and safety of X + N in Chinese pts with MBC refractory to anthracycline or taxane treatment in a phase II trial. Methods: 77 pts of a planned population of 60 pts were enrolled between Feb 2003 and Nov 2004. All pts had measurable MBC (WHO) recurrent after anthracycline or taxane treatment, Karnofsky PS ≥60, adequate bone marrow, renal and hepatic function. Pts received 3-weekly cycles of oral X 1000mg/m2 bid d1–14 + i.v. N 25mg/m2 d1&8, for at least 2 cycles. Pts with progressive disease went off study while those with complete response (CR), partial response (PR), or stable disease (SD) continued treatment for a maximum of 6 cycles. Results: Baseline characteristics of the 77 pts evaluable to date: median age 51 years (range 29–68); median Karnofsky PS 90 (range 70–100). Previous chemotherapy was: anthracycline (87%), paclitaxel/docetaxel (52%). Principal tumor sites were: lung (40%), liver (39%), lymph nodes (33%), thoracic wall (12%), breast (7%), other (3%). All pts received at least 2 cycles, 20 received 4 cycles and 47 received 6 cycles. The overall response rate was 22%, including 5 CR and 12 PR. At a median follow-up of 6 months (95% CI, 4.2–9.0), the median time to progression (TTP) is 6 months (95% CI, 3.5–9.0). The most common (≥10% pts) treatment-related grade 1/2 adverse events were: HFS (16%), nausea (12%), and SGPT abnormality (10%). Most adverse events improved or resolved after dose adjustment and/or suitable treatments. There were very few grade 3/4 adverse events, the most common being leucopenia (12%). Conclusions: X + N is active in pretreated MBC and its efficacy is confirmed in this study in Chinese pts. The combination is also well tolerated. No significant financial relationships to disclose.

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Phase II randomized study of gefitinib alone or plus vinorelbine every 2 weeks’ treatment in patients with adenocarcinoma of the lung who failed at least two regimens

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17095 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17095-17095

Author(s):

Y. Chen ◽

R. Perng ◽

C. Tsai ◽

J. Whang-Peng

Keyword(s):

Disease Progression ◽

Low Dose ◽

Randomized Study ◽

Objective Response ◽

Progression Free Survival ◽

Chinese Patients ◽

Lung Cancer Patients ◽

Ethnic Chinese ◽

Adenocarcinoma Of The Lung ◽

Treatment Objective

17095 Background: To assess the feasibility and the efficacy of adding chronic intermittent low-dose vinorelbine to gefitinib (Iressa) treatment for lung cancer patients with adenocarcinoma who failed 2 previous regimens of chemotherapy. Methods: Patients who had adenocarcinoma and failed at least 2 regimens, including taxanes and platinum, were enrolled and randomized into 2 arms: oral Iressa 250 mg daily (I) or vinorelbine 15 mg/m2 intravenous infusion day 1 and oral Iressa 250 mg daily from day 2 to 14, every 2 weeks (IV). From August 2004 to October 2005, 48 patients were enrolled. Results: Twenty-four patients were randomized into Iressa plus vinorelbine treatment. However, 3 patients refused vinorelbine treatment and received Iressa treatment only. Thus, 27 patients received I treatment and 21 patients received IV treatment. Objective response rates were 55.6% in I and 57.1% in IV. Any grade of leukopenia, neutropenia, and fatigue sensation was significantly higher in the IV arm (p=0.035, 0.001, 0.012, respectively). All the toxicities in both arms were generally mild and no toxic death occurred. However, many patients in the IV arm stopped V treatment before disease progression, including port-A occlusion in 4 patients (after 2, 5, 20, and 23 injections, respectively), mucositis in 1 (after 4 injections), and fatigue sensation in 1 (after 7 injections). After a median follow-up of 8 months, median time to disease progression was higher in IV than I (longer than 12 months vs. 7.1 months, p = 0.0271), more than half of the patients in each arm were still alive (p = 0.2269), and more than 9 patients in each arm survived longer than 1 year. Conclusions: Iressa is highly effective in ethnic Chinese patients with adenocarcinoma of the lung who have failed previous platinum and taxane treatment. The addition of low-dose V every 2 weeks produced a signiificantly better progression-free survival. Replacement of intravenous V with oral V should be considered to prevent the early termination of V treatment. No significant financial relationships to disclose.

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