Monotherapy In Chinese Patients Research Articles

Safety and efficacy of obinutuzumab in Chinese patients with B-cell lymphomas: a secondary analysis of the GERSHWIN trial

BackgroundPatients with relapsed/refractory B-cell lymphomas have limited treatment options. GERSHWIN is an open-label, single-arm, phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically documented CD20+ relapsed/refractory chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL). The primary outcome measure of pharmacokinetics has been previously reported. We now present data on the secondary endpoint measures (e.g., safety, and efficacy and pharmacodynamics).MethodsPatients received 1000 mg obinutuzumab intravenously on days 1, 8, and 15 of cycle 1 (CLL patients; first dose split over 2 days), and on day 1 of cycles 2–8. Each cycle lasted for 21 days; the treatment period was 24 weeks. All subjects receiving at least one dose of obinutuzumab were included in the analysis of safety, efficacy, as well as pharmacodynamics.ResultsA total of 48 patients (> 18 years of age) were enrolled (CLL: 12; DLBCL: 23; FL: 13). The subjects received a median of two lines of anticancer treatment prior to the enrollment. Thirty-five patients (72.9%) had at least one adverse event (AE). The most frequent AE was infusion-related reactions (15 patients; 31.3%), followed by pyrexia (11 patients; 22.9%). Treatment-related AEs were reported in 28 patients (58.3%), and included one death (interstitial lung disease). End-of-treatment (EoT) response rate was 33.3%. Best overall response rate was 47.9%. Most CLL patients achieved a partial response at EoT (58.3%). CD19+ depletion occurred in 75.0% of the patients with CLL, and all patients with FL and DLBCL.ConclusionsThe safety and efficacy of obinutuzumab monotherapy in Chinese patients with B-cell lymphomas were similar to that observed in previous studies in non-Chinese patients; no new safety signals were observed.Clinical trial registration ID NCT01680991

Safety and tolerability profile of raltitrexed in Chinese patients with locally advanced or recurrent and metastatic colorectal cancer: A phase IV trial.

571 Background: The clinical benefit and safety profile associated with raltitrexed in patients with advanced colorectal cancer (CRC) were established. However, safety information of raltitrexed in Chinese patients is rare. We aimed to assess the safety of raltitrexed monotherapy in Chinese patients with advanced CRC. Methods: This single-arm, open-label, multi-center, phase IV trial was conducted in 13 hospitals across China between March 2011 and July 2014. Patients with locally advanced or recurrent and metastatic colorectal cancer (mCRC) received raltitrexed (3mg/m2) as a 15-min infusion on day 1, every 21 days. Treatment was continued until disease progression or unacceptable toxicity. The primary objective was safety and the secondary objectives were disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Results: A total of 215 patients were enrolled, and the safety was assessed in 205 patients. 92 patients had 394 Adverse events (AEs) during the study. A majority (94.4%) of AEs was grade 1/2 and only 5.3% was grade 3/4. Most AEs were either resolved spontaneously or treated successfully with standard medical interventions. Severe AEs were reported by 5.8% (12/205) of patients. The most commonly reported AEs were increase of transaminases, leukopenia, nausea and vomiting. Serum transaminase elevation, an important safety concern associated with raltitrexed therapy, were transient, self-limiting and manageable. No deaths were reported during the study. The DCR in second-line and third-line therapy by raltitrexed reached 49.5% and 37.4%, respectively. The median PFS in second-line and third-line therapy was 1.43 months and 1.47 months, respectively. The median OS was 13.6 months and 8.9 months, respectively. Conclusions: Raltitrexed monotherapy is a safe, well-tolerated and convenient therapy option for Chinese patients. The treatment-associated toxicity is manageable and does not lead to discontinuation of treatment in oncology practice.

Retrospective Analysis of the Efficacy and Safety of Sorafenib in Chinese Patients With Metastatic Renal Cell Carcinoma and Prognostic Factors Related to Overall Survival.

Sorafenib has been recommended as first- or second-line treatment for metastatic renal cell carcinoma (mRCC) by several guidelines. The objective of this study is to evaluate the efficacy of sorafenib monotherapy in Chinese patients with mRCC and determine the prognostic clinicopathologic factors associated with survival in these patients.This is a single-arm retrospective study conducted in 2 tertiary medical centers; 140 mRCC patients were enrolled between January 2007 and June 2014. Sorafenib was administered at a dose of 400 mg twice daily, and continued until disease progression, at which point the dose was increased to 600 or 800 mg twice daily, or the onset of an intolerable adverse drug event (ADE) that required dose reduction or temporary suspension of treatment.The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety.The median follow-up time was 32 months. The median OS and PFS were 24 months (range, 3-88 months) and 16 months (range, 0-88 months), respectively. Patients with clear cell carcinoma had a greater OS (P=0.001) whereas sarcomatoid differentiation (P=0.045) and disease progression (P=0.010) negatively impacted OS; time from kidney surgery or biopsy to initiation of sorafenib treatment was associated with PFS (P=0.027). Efficacy analysis revealed that 3 (2.1%) patients achieved complete responses, 28 (20.0%) patients experienced partial responses, 88 (62.9%) patients had stable disease, and 21 (15.0%) patients developed progressive disease. Moreover, the ORR was 22.1%, and the DCR was 85.0%. Most ADEs were classified as grades 1 or 2 with only 14 (10.0%) patients experiencing a severe ADE (grade 3).Sorafenib monotherapy can achieve promising OS and PFS for Chinese patients with mRCC, especially in those with clear cell carcinoma, with manageable adverse events.

Glargine insulin/gliclazide MR combination therapy is more effective than premixed insulin monotherapy in Chinese patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs.

The aim of this study is to compare the efficacy and safety of once-daily insulin glargine plus gliclazide modified release combination therapy versus twice-daily premixed insulin monotherapy in Chinese type 2 diabetic patients insufficiently controlled by oral antidiabetic agents. In a 12-week, multicenter, randomized, parallel-group clinical trial, patients with poor glycaemic control (fasting plasma glucose ≥ 7.0 mmol/L and 7.5% < haemoglobin A1c ≤ 10%) on oral antidiabetic drugs were randomized to the treatment groups for combination therapy (n = 52) or monotherapy (n = 53). Continuous glucose monitoring was carried out over two 72-h periods, at the beginning and the end of the study, and the data were used to calculate the 24-h mean blood glucose, mean amplitude of glycaemic excursions, standard deviation of blood glucose, and the mean of daily differences. The mean haemoglobin A1c decrease from baseline to study end was significant for both treatment groups (combination therapy: -1.23 ± 0.92%; insulin monotherapy: -1.02 ± 1.04%); moreover, the combination therapy group showed a significantly more robust haemoglobin A1c decrease (p = 0.0308). Both therapies significantly reduced the 24-h mean blood glucose (both, p < 0.001), but neither produced a significant effect on glycaemic variability, calculated as mean amplitude of glycaemic excursions, standard deviation of blood glucose, and mean of daily differences. In addition, the effects on rates of hypoglycaemic episodes were similar between the two therapies. Chinese patients with type 2 diabetes inadequately controlled with oral antidiabetic agents attained greater benefit from once-daily insulin glargine plus gliclazide modified release regimen than from a twice-daily premixed insulin regimen.

Pharmacokinetic profile and first preliminary clinical evaluation of bendamustine in Taiwanese patients with heavily pretreated indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma.

Prior studies found bendamustine is efficacious in patients with indolent B-cell non-Hodgkin lymphoma (NHL). To date, no studies have reported the efficacy of bendamustine in a Chinese population. This multicentre phase II trial evaluated the pharmacokinetics (PK), safety and efficacy of bendamustine monotherapy in Chinese patients in Taiwan with pretreated indolent B-cell NHL or mantle cell lymphoma (MCL). For PK assessments, patients were randomized (n = 16; 11 with indolent B-cell NHL and five with MCL) to 90 or 120 mg/m(2) of bendamustine for the first cycle. Plasma levels of bendamustine and its two metabolites were analyzed. For efficacy and safety evaluations, bendamustine 120 mg/m(2) was given to all patients every 3 weeks starting at cycle 2 for a minimum of a total of six cycles. The median age of patients was 61.7 years, and the majority were men (75%). The median number of prior treatments was 4 (range, 1-9 regimens), and all patients were previously treated with rituximab. Bendamustine plasma concentration peaked near the end of infusion and was rapidly eliminated with a mean elimination half-life (t(1/2)) of 0.67-0.8 h. Of the evaluable patients (n = 14), the overall response rate was 78.6%, including 7.2% of patients having a complete response. Mean progression-free survival was 27.5 weeks. The most common grade 3-4 adverse events were leucopenia (56.3%), neutropenia (56.3%) and thrombocytopenia (25%). In conclusion, bendamustine was efficacious and well tolerated in Taiwanese patients with indolent NHL and MCL with a similar PK profile to that of other populations.

NeuroD1A45T andPAX4R121W polymorphisms are associated with plasma glucose level of repaglinide monotherapy in Chinese patients with type 2 diabetes

We aimed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients. Three hundred and sixty-eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism. Forty-three patients with various genotypes were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg day(-1)). Fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin, fasting and postprandial serum insulin (FINS, PINS), homeostasis model assessment for insulin resistance, serum triglyceride, total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were determined before and after repaglinide treatment. The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [13.45 vs. 6.82%, P < 0.01, odds ratios = 2.342 (1.365, 4.019), P= 0.002]. Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45T polymorphism showed higher FINS (13.46 ± 12.57 vs. 10.04 ± 7.09 mU l(-1) , P < 0.05) (11.67, 14.83 vs. 8.38, 11.37) and PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than individuals with the T allele. The PAX4 R121W R allele carriers had higher PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele of NeuroD1/BETA2 A45T polymorphisms had attenuated efficacy on fasting plasma glucose (-2.79 ± 2.14 vs.-0.99 ± 1.80 mmol l(-1), P < 0.01) (-3.53, -1.84 vs.-1.99, -0.13) and postprandial plasma glucose (-6.71 ± 5.90 vs.-2.54 ± 3.39 mmol l(-1), P < 0.01) (-9.28, -4.62 vs.-4.34, -0.84). Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (-6.53 ± 6.52 vs.-2.95 ± 1.17 mmol l(-1), P < 0.05) (-8.20, -4.89 vs.-3.92, -1.20). The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy.

Comparison of the retention rates between carbamazepine and valproate as an initial monotherapy in Chinese patients with partial seizures: A ten-year follow-up, observational study

Purpose To compare the long-term retention rates of the two most commonly prescribed antiepileptic drugs (AEDs), carbamazepine (CBZ) and valproate (VPA) as an initial monotherapy in Chinese patients with partial seizures. Methods This is a retrospective, observational study in a tertiary epilepsy centre. Overall, 584 patients were followed during a ten-year period. Kaplan–Meier survival analysis was used to estimate the cumulative probability of retention. Cox proportional hazard model was used to analyze the risk factors for retention rate. Results The calculated retention rates estimated by Kaplan–Meier survival analysis showed no difference between CBZ and VPA ( p = 0.074). During the time period from the first six months to two years, the lack of efficacy (LE) that led to drug discontinuation was 10.7% for CBZ compared to 4.5% for VPA ( p = 0.004). The adverse effects (AEs) that led to discontinuation was 2.4% for CBZ compared to 6.3% for VPA ( p = 0.025). Clinical control that led to discontinuation was 15.9% for CBZ compared to 7.5% for VPA ( p = 0.001). The five-year remission rate was higher in the CBZ group (33.3%) than in the VPA group (23.2%, p = 0.006). Yet in the complex partial seizure subgroup, there was no significant difference between the two drugs ( p = 0.61). Conclusion Compared with VPA, patients treated with CBZ were more likely to discontinue treatment for LE, and were less likely to discontinue for AEs; however, the two differences above only occurred in the time period between the first six months to two years of treatment. Long-term treatment with CBZ appeared to be more effective in terms of five-year remission and clinical control than VPA.

Long-term retention rate of topiramate as initial monotherapy in Chinese patients with newly diagnosed epilepsy: A prospective, observational study

This is a large-sample, prospective, long-term observational study to assess the retention rate of topiramate as initial monotherapy in Chinese patients with newly diagnosed epilepsy. The retention rate was calculated by Kaplan-Meier method using intention-to-treatment analysis. Cox proportional hazard models were used to analyze the risk factors for retention rate. A total of 229 patients were enrolled into this study. The retention rate was 75.5% at 1 year, 47% at 6 years. Three risk factors for treatment failure were female gender, rural residence, and frequent seizures before treatment. Four predominant causes leading to treatment failure were: lack of efficacy (7.4%), adverse effects (10.9%), follow-up loss (15.7%), and subjective misunderstanding (8.3%). Adverse effects occurred in 129 (56.3%) patients, with 7 (3.1%) patients suffered from renal calculus. This study suggests the long-term retention rate of topiramate as initial monotherapy is high in Chinese patients. Lower initial dose, lower target dose and slower titration contribute to better tolerability. Frequent abdominal ultrasound for detecting renal calculus is necessary. Rural patients and patients with poor education level should be paid more attention by physicians to ensure continued therapy.

Evaluation of efficacy and safety of gefitinib as monotherapy in Chinese patients with advanced non-small cell lung cancer and very poor performance status

BackgroundThis paper reports the outcome of gefitinib for Chinese advanced NSCLC patients with poor performance status (PS) at the Peking Union Medical College Hospital.MethodsFrom Oct 2002 to Apr. 2006, 42 advanced NSCLC patients with PS 3/4 received gefitinib 250 mg/day treatment. Median survival (MS) were calculated using the Kaplan-Meier method and a Cox regression model was used to find main factors affecting MS.ResultsAdverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were rash 72.2% (26/42) and diarrhea 44.4% (26/42). The objective tumor response rate and stable disease rate were 40.5% and 26.2% respectively, and median survival(MS) of all patients was 10.1 months (95% confidential interval CI, 3.4 ~ 16.8), and progression-free survival(PFS) was 5.7 months (95% CI, 4.5 ~ 6.9). The MS were significantly related with objective response of gefitinib. Objective responses was significantly related with rashes induced with gefitinib.ConclusionOur study suggest that treatment with gefitinib may be well tolerated and beneficial for Chinese patients with poor PS, and the safety and efficacy were similar to patients with good PS.

The association of adiponectin allele 45T/G and −11377C/G polymorphisms with Type 2 diabetes and rosiglitazone response in Chinese patients

Rosiglitazone is able to increase serum adiponectin levels significantly in Type 2 diabetic patients. :The role of genetic factors that determine the marked interindividual variability in glucose-lowering efficacy of rosiglitazone in Chinese patients is not known. The current study was designed to evaluate the impact of the adiponectin common allele 45T/G and -11377C/G polymorphisms on the response to rosiglitazone monotherapy in Chinese patients with Type 2 diabetes (T2D). The genetic polymorphisms of adiponectin alleles 45T/G and -11377C/G as well as their common diplotypes are significantly associated with an attenuated fasting plasma glucose, postprandial plasma glucose and homeostasis model assessment for insulin resistance as well as an enhanced adiponectin concentration in Chinese patients with T2D after rosiglitazone treatment. AIMS The aim of the present study was to evaluate the impact of adiponectin allele T45G and C-11377G genetic polymorphisms on efficacy of rosiglitazone in Chinese patients with type 2 diabetes (T2D). Patients with T2D (n = 255) and 120 healthy volunteers were enrolled to identify 45T/G and -11377C/G genotypes by polymerase chain reaction-restriction fragment length polymorphism assay. Forty-two T2D patients with different 45T/G or -11377C/G genotypes received orally rosiglitazone as a single-dose therapy (4 mg day-1 p.o.) for 12 weeks. Serum triglyceride, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin, fasting serum insulin, postprandial serum insulin, total cholesterol, homeostasis model assessment for insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol (HDL-c) and adiponectin concentration were determined before and after rosiglitazone treatment. We showed an attenuated rosiglitazone effect in patients with -11377CG+GG heterozygote genotype on FPG, PPG, HOMA-IR compared with -11377CC homozygote genotype. However, we found an enhanced rosiglitazone effect on serum adiponectin concentration in patients with -11377CC homozygote genotype compared with -11377CG+GG heterozygote genotype (P = 0.000) and in patients with 45TG + GG heterozygote genotype compared with 45TT homozygote genotype (P = 0.018). Finally, our results showed that there was an enhanced effect in patients with -11377/45 CGTT diplotype compared with other discovered diplotypes on FPG (P = 0.001) and PPG (P = 0.003) after rosiglitazone treatment. These data suggest that the adiponectin allele 45T/G and -11377C/G polymorphisms are significantly associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese patients with T2D.

Efficacy and safety of gefitinib as monotherapy for Chinese patients with advanced non-small cell lung cancer

Efficacy and safety of gefitinib as monotherapy for Chinese patients with advanced non-small cell lung cancer

Evaluation of efficacy and safety of ZD1839 as monotherapy for Chinese patients with advanced non-small cell lung cancer: Experience from a compassionate-use programme

7254 Background: The tolerability and efficacy of ZD1839 have been explored extensively in the West and Japan. This paper reports the outcome of ZD1839 for Chinese patients with advanced NSCLC from Expanded Access Programme (EAP) at the Peking Union Medical College Hospital. Methods: From Oct 2002 to Oct 2004, 151 patients with advanced NSCLC received oral ZD1839 250 mg/day treatment. 90 (59.6%) men and 61 (40.4%) women between 25 and 85 years of age. 31 (20.5%) patients had squamous cell carcinoma, 88 (58.3%) adenocarcinoma, 21(13.9%) bronchioloalveolar carcinoma, 6(4.0%) adenosquamous carcinoma, and 5(3.3%) unspecified. 15 patients had no history of chemotherapy, 34 had no disease progression after chemotherapy, and 102 failed to prior one or more regimens. Median overall survival (OS) were calculated using the Kaplan-Meier method and a log-rank test was used to detect differences OS between strata. Results: Adverse events (AEs) were generally mild (grade1 and 2) and reversible. The most frequent AEs were rash(73.6%), diarrhea(36.4%), nasal/oral hemorrhage(10.7%), anorexia(10.0%), and transaminase elevating(7.1%). The objective tumour response rate and stable disease rate was 29.8%(95% confidence interval [CI], 22.5–37.1) and 36.4%(95% CI, 28.8–44.0) respectively, and median overall survival(OS) was 15.3 months (95% CI, 11.5–19.2). The median OS were significantly related with ECOG scores, pathology types, efficacy of ZD1839, changes of symptoms and rash. Partial responses was significantly higher in women, non-smokers, patients with adenocarcinomas, and patients with rashes induced by ZD1839. The median progression-free survival (PFS) and median OS for patients who failed to prior regimens were 8.9 months (95% CI, 6.7–11.0) and 11.7 months (95% CI, 8.3–15.2). Conclusions: Our study suggest that treatment with ZD1839 may be well tolerate and beneficial for some Chinese patients after failure of prior chemotherapy. No significant financial relationships to disclose.

Evaluation of safety and efficacy of ZD1839 as monotherapy for Chinese patients with advanced non-small cell lung cancer

7093 Background: The aim of the study was to evaluate the safety and efficiency of ZD1839 for Chinese patients with advanced NSCLC. Methods: From Dec 2002 to Aug 2003, 40 eligible patients with unresectable NSCLC (male 25, female 15, Aged from 28–85yrs, Bronchioloalveolar carcinoma 10, Other Adenocarcinoma 21, Squamous cell carcinoma 7, Unspecified 2)enrolled in the study. ZD1839 was administrated orally at the dose of 250 mg/day at about the same time everyday without interruption unless disease progressed or unacceptable adverse event occurred. The impact of treatment on disease-related symptoms and quality of life (QoL) was evaluated with Chinese version of EORTC QLQ-C30 and QLQ-LC13. Results: Daily oral dose of 250mg of ZD1839 was well tolerated in Chinese patients. Adverse events were generally mild (grade 1 and 2) and reversible. The most frequent adverse events were acne-like rash (62.5%) and diarrhea (30.0%). No patient withdrew from the study due to drug-related adverse event. The objective tumor response rate was 32.5%. Disease control rate was 62.5%. Multivariate analysis showed tumor response was associated with bronchioloalveolar carcinoma. The median progression-free survival (PFS) was 22.5w. At the data cutoff, 26 (65%) patients were still alive with median follow-up period of 30w (range: 2 to 60). The QoL response rates for five functioning scales and global QoL varied from 56% to 88%. Main symptom response rates varied from 44% to 84%. QoL and symptom response were correlated with objective tumor response. Conclusion: Our study showed the safety and efficacy of ZD1839 as monotherapy for Chinese patients with advanced NSCLC. Treatment with ZD1839 was associated with remarkable symptom release and improvement of QoL. Further clinical study with ZD1839 can be conducted in Chinese patients with NSCLC. No significant financial relationships to disclose.

Evaluation of safety and efficacy of ZD1839 as monotherapy for Chinese patients with advanced non-small cell lung cancer

7093 Background: The aim of the study was to evaluate the safety and efficiency of ZD1839 for Chinese patients with advanced NSCLC. Methods: From Dec 2002 to Aug 2003, 40 eligible patients with unresectable NSCLC (male 25, female 15, Aged from 28–85yrs, Bronchioloalveolar carcinoma 10, Other Adenocarcinoma 21, Squamous cell carcinoma 7, Unspecified 2)enrolled in the study. ZD1839 was administrated orally at the dose of 250 mg/day at about the same time everyday without interruption unless disease progressed or unacceptable adverse event occurred. The impact of treatment on disease-related symptoms and quality of life (QoL) was evaluated with Chinese version of EORTC QLQ-C30 and QLQ-LC13. Results: Daily oral dose of 250mg of ZD1839 was well tolerated in Chinese patients. Adverse events were generally mild (grade 1 and 2) and reversible. The most frequent adverse events were acne-like rash (62.5%) and diarrhea (30.0%). No patient withdrew from the study due to drug-related adverse event. The objective tumor response rate was 32.5%. Disease control rate was 62.5%. Multivariate analysis showed tumor response was associated with bronchioloalveolar carcinoma. The median progression-free survival (PFS) was 22.5w. At the data cutoff, 26 (65%) patients were still alive with median follow-up period of 30w (range: 2 to 60). The QoL response rates for five functioning scales and global QoL varied from 56% to 88%. Main symptom response rates varied from 44% to 84%. QoL and symptom response were correlated with objective tumor response. Conclusion: Our study showed the safety and efficacy of ZD1839 as monotherapy for Chinese patients with advanced NSCLC. Treatment with ZD1839 was associated with remarkable symptom release and improvement of QoL. Further clinical study with ZD1839 can be conducted in Chinese patients with NSCLC. No significant financial relationships to disclose.