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ABSTRACT: To evaluate effects of UDP-glucuronosyltransferase1A1 (UGT1A1) and thymidylate synthetase (TS) gene polymorphisms on irinotecan in metastatic colorectal cancer (mCRC).
Two irinotecan- and fluorouracil-based regimens, FOLFIRI and IFL, were selected as second-line therapy for 138 Chinese mCRC patients. Genomic DNA was extracted from peripheral blood samples before treatment. UGT1A1 and TS gene polymorphisms were determined by direct sequencing and restriction fragment length polymorphism, respectively. Gene polymorphisms of UGT1A1*28, UGT1A1*6 and promoter enhancer region of TS were analyzed. The relationship between genetic polymorphisms and clinical outcome, that is, response, toxicity and survival were assessed. Pharmacokinetic analyses were performed in a subgroup patients based on different UGT1A1 genotypes. Plasma concentration of irinotecan and its active metabolite SN-38 and inactive metabolite SN-38G were determined by high performance liquid chromatography. Differences in irinotecan and its metabolites between UGT1A1 gene variants were compared.
One hundred and eight patients received the FOLFIRI regimen, 29 the IFL regimen, and one irinotecan monotherapy. One hundred and thirty patients were eligible for toxicity and 111 for efficacy evaluation. One hundred and thirty-six patients were tested for UGT1A1*28 and *6 genotypes and 125 for promoter enhancer region of TS. Patients showed a higher frequency of wild-type UGT1A1*28 (TA6/6) compared with a Caucasian population (69.9% vs 45.2%). No significant difference was found between response rates and UGT1A1 genotype, although wild-type showed lower response rates compared with other variants (17.9% vs 24.2% for UGT1A1*28, 15.7% vs 26.8% for UGT1A1*6). When TS was considered, the subgroup with homozygous UGT1A1*28 (TA7/7) and non-3RG genotypes showed the highest response rate (33.3%), while wild-type UGT1A1*28 (TA6/6) with non-3RG only had a 13.6% response rate, but no significant difference was found. Logistic regression showed treatment duration was closely linked to clinical response. In toxicity comparison, UGT1A1*28 TA6/6 was associated with lower incidence of grade 2-4 diarrhea (27.8% vs 100%), and significantly reduced the risk of grade 4 neutropenia compared with TA7/7 (7.8% vs 37.5%). Wild-type UGT1A1*6 (G/G) tended to have a lower incidence of grade 3/4 diarrhea vs homozygous mutant (A/A) genotype (13.0% vs 40.0%). Taking UGT1A1 and TS genotypes together, lower incidence of grade 2-4 diarrhea was found in patients with non-3RG TS genotypes, when TA6/6 was compared with TA7/7 (35.3% vs 100.0%). No significant association with time to progression (TTP) and overall survival (OS) was observed with either UGT1A1 or TS gene polymorphisms, although slightly longer TTP and OS were found with UGT1A1*28 (TA6/6). Irinotecan PK was investigated in 34 patients, which showed high area under concentration curve (AUC) of irinotecan and SN-38, but low AUC ratio (SN-38G / SN-38) in those patients with UGT1A1*28 TA7/7.
A distinct distribution pattern of UGT1A1 genotypes in Chinese patients might contribute to relatively low toxicity associated with irinotecan and 5-fluorouracil in mCRC patients.
World Journal of Gastroenterology 12/2012; 18(45):6635-44. · 2.47 Impact Factor
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ABSTRACT: Icotinib is a new oral epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI). The most frequent side-effects of icotinib include rash and diarrhea. Hand-foot syndrome (HFS) induced by EGFR-TKI is rare. The present study describes, for the first time, HFS induced by high-dose icotinib in a 65-year old female with metastatic lung adenocarcinoma. The patient developed HFS during the first week of icotinib treatment with characteristic clinical presentation. HFS regressed after icotinib dose-reduction was initiated. HFS may occur with icotinib, especially when administered in high doses.
Oncology letters 12/2012; 4(6):1341-1343. · 0.11 Impact Factor
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ABSTRACT: Objective: To investigate the expression of RRM1 and ERCC1 genes in tumor tissues and peripheral blood lymphocytes of advanced non-small cell lung cancer (NSCLC). Methods: Tissue and peripheral blood samples were collected from 49 advanced NSCLC patients treated with gemcitabine plus carboplatin. The expressions of RRM1 and ERCC1 mRNA in tumor tissue and peripheral lymphocytes were detected by real-time fluorescent quantitative PCR. The relationship of gene expression with clinical characteristics,chemotherapy response and prognosis was analyzed. Results: The RRM1 expression in tumor tissues was positively correlated with that in peripheral blood lymphocytes,while no significant correlation was observed between ERCC1 expression in tumor tissues and that in peripheral blood (rs=0.332 and 0.258; P=0.020 and 0.073, respectively). The expression of RRM1 and ERCC1 in tumor tissues peripheral lymphocytes was synchronous (rs=0.634 and 0.351; P<0.001 and 0.013, respectively). There was no significant correlation of gene expression with gender, age, smoking status, performance status, clinical stages and histological types of patients (P>0.05). Significant difference was found in response rate to chemotherapy (P<0.05,P<0.01,P<0.05),median survival time (P<0.05,P<0.01,P<0.05) and 1-year survival rate (P<0.01,<0.05,P<0.05) between patients with low RRM1 and ERCC1 expression levels in tumor tissues or low RRM1 expression levels in peripheral blood and those with high RRM1 and ERCC1 expression levels. The patients with low ERCC1 expression levels in tumor tissues gained higher 2-year survival rate (P<0.05). There was no correlation of the expression of ERCC1 in peripheral blood with the response to chemotherapy and prognosis (P>0.05). Conclusion: The expression of RRMI and ERCC1 genes in tumor tissues and RRM1 in peripheral blood lymphocytes is closely correlated with the response to chemotherapy and prognosis of patients with advanced NSCLC treated with gemcitabine plus carboplatin.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 09/2012; 41(5):540-6.
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ABSTRACT: Icotinib is a new oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). We report on a 49-year-old man with recurrent lung adenocarcinoma treated with icotinib. The patient obtained a partial remission in 4 weeks that was maintained 14 months. Retrospective examination of EGFR mutations confirmed he had a sensitive mutation (exon 19 deletion). This case supports that icotinib has great efficacy in advanced non-small cell lung cancer with sensitive EGFR mutations.
Tumori. 07/2012; 98(4):102e-4e.
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ABSTRACT: Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis, and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF protein overexpression with the clinical outcome in patients with gastric cancer, but yielded conflicting results. The prognostic significance of VEGF overexpression in gastric cancer remains controversial. Electronic databases updated to July 2011 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF overexpression and survival of patients with gastric cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 30 studies (n = 3,999 patients) that evaluated the correlation between VEGF overexpression detected by immunohistochemistry and survival in patients with gastric cancer. Combined hazard ratios suggested that VEGF-A overexpression had an unfavorable impact on overall survival (OS) (HR [hazard ratio] = 1.49, 95 % CI [confidence interval]: 1.22-1.77) and disease free survival (DFS) (HR = 1.85, 95 % CI: 1.38-2.32) in patients with gastric cancer. However, VEGF-C overexpression did not significantly correlate with OS (HR = 1.24, 95 % CI: 0.92-1.56) or DFS (HR = 1.15, 95 % CI: 0.78-1.52). VEGF-D is an unfavorable indicator of OS (HR = 1.68, 95 % CI: 1.02-2.34) and DFS (HR = 1.88, 95 % CI: 1.07-2.70) in patients with gastric cancer. VEGF-A and VEGF-D overexpression indicated a poor prognosis for patients with gastric cancer. VEGF-C overexpression was not associated with poor prognosis in patients with gastric cancer. The prognostic value of VEGF on survival still needs further larger prospective trials to be confirmed.
Molecular Biology Reports 06/2012; 39(10):9473-84. · 2.93 Impact Factor
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ABSTRACT: S-1 is an oral antitumor agent that contains tegafur, which is converted to fluorouracil (5-FU) in the human body. Cytochrome P450 2A6 (CYP2A6) is the principal enzyme responsible for bioconversion of tegafur to 5-FU. A number of CYP2A6 polymorphisms have been associated with variations in enzyme activity in several ethnic populations. The CYP2A6*4C allele leads to deletion of the entire CYP2A6 gene, and is the main finding in patients with reduced CYP2A6 enzymatic activity. Thus, the aim of our study was to evaluate the allele frequencies of CYP2A6 polymorphisms in a population with cancer of the digestive system. We developed a simple screening method, which combined TA cloning and direct-sequencing, to detect CYP2A6 genetic polymorphisms in Chinese patients with cancers of the digestive system. A total of 77 patients with various types of digestive system cancers were screened for CYP2A6 genetic polymorphisms. The allele frequencies of CYP2A6*1A, CYP2A6*1B and CYP2A6*4C in the 77 patients screened were 62, 42 and 13%, respectively. Frequencies of the homozygous genotypes for CYP2A6*1A and CYP2A6*4C were 27 and 12%, respectively. As expected, patients that were determined to be homozygous for CYP2A6*4C exhibited the characteristic chemotherapy efficacy and toxicity profiles. The TA cloning-based direct sequencing method facilitated allele frequency and genotyping determination for CYP2A6*1A, 1B and 4C of cancer patients. The findings indicated that the population carries a high frequency of the CYP2A6*4C homozygous genotype. Thus, the reduced efficacy of standard chemotherapy dosage in Chinese cancer patients may be explained by the lack of CYP2A6-mediated S-1 bioconversion to 5-FU.
Oncology Reports 05/2012; 27(5):1606-10. · 1.84 Impact Factor
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ABSTRACT: To comparatively evaluate the prognostic or predictive value of ribonucleotide reductase M1 (RRM1) and excision repair cross-complementation 1 (ERCC1) gene expression in peripheral blood versus tumor tissue from patients with advanced non-small cell lung cancer (NSCLC) treated by gemcitabine/platinum chemotherapy.
A total of 49 patients with advanced NSCLC receiving gemcitabine plus carboplatin chemotherapy were studied. RRM1 and ERCC1 mRNA levels in the peripheral blood and tumor tissue were determined by real-time fluorescent quantitative PCR. The relationships between gene expression and clinical and pathological factors, response to chemotherapy as well as prognosis, were evaluated.
RRM1 expression in peripheral blood and tumor tissue, but not ERCC1 expression, was found to be positively correlated (r = 0.332, 0.258; P = 0.020, 0.073; respectively). RRM1 and ERCC1 expression levels were nearly synchronous in both peripheral blood (r = 0.351; P = 0.013) and tumor tissue (r = 0.634; P < 0.001). Neither was correlated with clinical and pathological factors.
with low RRM1 expression in peripheral blood or low RRM1 or ERCC1 expression in tumor tissue experienced better response to chemotherapy (50.0 vs. 16.0%, 50.0 vs. 16.0%, and 54.2 vs. 12.0%; P = 0.012, 0.012, and 0.003; respectively), longer median survival (18.5 vs. 13.0 months, 18.5 vs. 12.0 months, and 19.8 vs. 12.5 months; P = 0.043, 0.014 and 0.007; respectively), and longer progression-free survival (6.0 vs. 4.0 months, 7.8 vs. 3.9 months, and 5.8 vs. 3.8 months; P = 0.044, 0.016, and 0.008; respectively). Cox multivariate regression analysis showed that ERCC1 expression in tumor tissue was independent indicator for overall survival.
Advanced NSCLC patients with low RRM1 mRNA expression both in peripheral blood and in tumor tissue could benefit from gemcitabine/carboplatin chemotherapy. ERCC1 mRNA expression in tumor tissue may be a predictive and prognostic indicator in advanced NSCLC patients receiving gemcitabine/carboplatin chemotherapy.
Cancer Chemotherapy and Pharmacology 02/2012; 69(5):1277-87. · 2.83 Impact Factor
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ABSTRACT: Primitive neuroectodermal tumor (PNET) arising in the urinary bladder is extremely rare. Here, we report a case of primary PNET of the urinary bladder in an aged Asian man that showed an aggressive clinical course. A 74-year-old man presented with frequency, dysuria, and gross hematuria. Pelvic computed tomography showed a mass in the urinary bladder. Microscopically, the tumor revealed sheets of uniform, small, round, blue cells, and immunohistochemical examination demonstrated primary PNET of the urinary bladder. Palliative chemotherapy was administered. After three courses of chemotherapy, his disease progressed and he died 4 months after diagnosis.
Medical Oncology 12/2011; 28 Suppl 1:S388-91. · 2.14 Impact Factor
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ABSTRACT: Retroperitoneal primary mucinous adenocarcinoma (RPMA) is extremely rare and the histogenesis of this tumor remains unclear. There is no consensus on the appropriate treatment for RPMA. Surgical resection is standard for the treatment of RPMA, whereas the benefits of chemotherapy with regard to this tumor remain to be established. This case report concerns a 21-year-old female individual with RPMA. The patient initially presented with chronic lower back pain and weight loss. Additionally, carcinoembryonic antigen (CEA) levels were found to be elevated. A computed tomography scan revealed a mass in the abdominal cavity. Consequently, laparotomy was performed, which revealed a well-defined tumor in the right retroperitoneum. Chemotherapy as a monotherapy was not considered as a viable treatment option. Therefore, the patient was initially administered a combined treatement of oxaliplatin and 5-fluorouracil. This treatment was then changed to paclitaxel and 5-fluorouracil. Findings showed a decrease in the CEA serum levels, indicating that this combination treatment may be efficacious in the treatment of RPMA since local recurrence following surgical resection was well controlled with chemotherapy.
Oncology letters 07/2011; 2(4):633-636. · 0.11 Impact Factor
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ABSTRACT: Celastrol is a natural compound extracted from the traditional Chinese medicinal herb, Tripterygium wilfordii Hook. It has attracted interests for its potential anti-inflammatory and antitumor effects. However, the molecular mechanisms of celastrol-induced apoptosis in cancer cells remain unclear. In this study, we investigated the effects of celastrol on the human non-small-cell lung cancer (NSCLC) cell line A549 in vitro. Celastrol caused a dose- and time-dependent growth inhibition of A549 cells with an IC(50) of 2.12 μM at 48 h treatment. Celastrol induced A549 cells apoptosis as confirmed by annexin V/propidium iodide staining and DNA fragmentation. Celastrol-induced apoptosis was characterized by cleavage of caspase-9, caspase-8, caspase-3, and PARP protein, increased Fas and FasL expression, and a reduction in the mitochondrial membrane potential. Furthermore, celastrol induced the release of cytochrome c. Celastrol also up-regulated the expression of pro-apoptotic Bax, down-regulated anti-apoptotic Bcl-2, and inhibited Akt phosphorylation. These results demonstrate that celastrol can induce apoptosis of human NSCLC A549 cells through activation of both mitochondria- and FasL-mediated pathways.
Toxicology in Vitro 04/2011; 25(5):1027-32. · 2.78 Impact Factor
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Jing Deng,
Wei Jia Fang,
Xiao Chen Zhang,
Dong Ping Wu,
Hong Ming Fang,
Jing Chen,
Jiong Qian,
Hai Bo Mou,
Bin Bin Chu, Nong Xu,
Li Song Teng
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ABSTRACT: A phase II clinical trial was performed to evaluate the efficacy and safety of gefitinib on pretreated Chinese female non-small-cell lung cancer (NSCLC) patients. Chinese female patients with locally advanced or metastatic NSCLC who failed at least one platinum-based chemotherapy received gefitinib monotherapy (250 mg/day) between April 2002 and January 2010. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS) and progression-free survival (PFS). Of the 40 evaluable female patients, the ORR was 62.5%. All patients have responded with one (2.5%) complete response, 24 (60%) partial response, 12 (30%) stable disease, and 3 (7.5%) progressive disease. The OS and PFS were 20 months (95% CI: 11.9-28 months) and 13 months (95% CI: 8.0-17.9 months), respectively. Survival (OS and PFS) were longer in patients with good performance status and in patients older than 65 years (P < 0.05). The most frequently observed toxicities were rash/dry skin (80%), diarrhea (42.5%), and vomiting/anorexia (32.5%). Four patients developed grade 3 toxicities (rash and diarrhea) but did not require either dose reduction or discontinuation. Gefitinib is a highly effective and well-tolerated agent for Chinese women with pretreated advanced NSCLC.
Medical Oncology 03/2011; 29(2):595-9. · 2.14 Impact Factor
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ABSTRACT: The goal of this study was to assess the safety and tolerability of icotinib hydrochloride (BPI-2009H), a new selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), and to explore its pharmacokinetics (PK) and clinical activity in patients with advanced solid tumors, mainly those with non-small-cell lung cancer (NSCLC) after the failure of the prior platinum-based chemotherapy.
Different doses of oral icotinib were administered once every 8 h (Q8H) for a 28-continuous-day cycle until disease progression and or undue toxicity was observed. PK studies of subjects' blood were performed during cycle one (day 1 through 28). Patients aged ≥18 and ≤70 years with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 and adequate organ functions eligible for the study. Tumor responses were assessed by Response Evaluation Criteria in Solid Tumors (RECIST). K-ras and EGFR mutations in the extracted DNA of fourteen specimens were examined using PCR-based direct sequencing assay.
Thirty-six patients were enrolled in the study. PK analysis demonstrated that the mean elimination half-life of icotinib was 6 h, and the T(max) was around 2 h. The steady-state concentration of icotinib administered at a dose of 125 mg once every 8 h (Q8H) was significantly higher than that achieved by a dose of 100mg Q8H. The most frequent treatment-related adverse events (TRAEs) were an acne-like (folliculitis) rash (16/36, 44.4%), diarrhea (8/36, 22.2%) and a decrease in white blood cells (4/36, 11.1%). The maximum-tolerated dose (MTD) was not reached. Among 33 patients with NSCLC, 7 patients exhibited a partial response, 7 showed stable disease at the 24 weeks. Among 14 patients undergoing DNA sequence for K-ras and EGFR mutations, 3 with K-ras mutation presented 2 stable disease (SD) and 1 partial response (PR), 5 with EGFR exon 19 or 21 mutation 2 PR and 3 SD within 4 weeks.
Oral icotinib was generally well tolerated, with manageable and reversible adverse events (AEs) and showed positive clinical anti-tumor activities in patients with advanced NSCLC. The recommended dose for phase II/III studies with icotinib is 125 mg or 150 mg Q8H.
Lung cancer (Amsterdam, Netherlands) 12/2010; 73(2):195-202. · 3.14 Impact Factor
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Journal of the National Medical Association 07/2010; 102(7):654-6. · 1.16 Impact Factor
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Han Ying Bao,
Wei Jia Fang,
Xiao Chen Zhang,
Gen Ming Shi,
Sui Huang,
Lan Fang Yu,
Jin Chen,
Hai Bo Mou,
Jing Deng,
Peng Shen, Nong Xu
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ABSTRACT: To evaluate the efficacy and safety of FOLFIRI regimen in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.
The FOLFIRI regimen consisted of intravenous infusion of irinotecan 180 mg/m(2) on day 1 plus leucovorin (LV) 400 mg/m(2) on day 1 plus 5-fluorouracil (5-FU) 400 mg/m(2) bolus on day 1 plus 46-hour intravenous infusion of 5-FU 2,400 mg/m(2), every 2 weeks as one cycle. The main selection criterion for this study was the advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.
Of the 57 evaluable patients for efficacy, 4 (7.5%) had a partial response, 36 (67.9%) had stable disease, and 13 (24.5%) had progressive disease. Median progression-free survival was 4.8 months (95% CI 3.9-5.7 months), and median overall survival was 7.8 months (95% CI 13.1-16.5 months). Safety analysis was based on the data of 57 evaluable patients. The most frequently observed grade 3 or 4 toxicities were neutropenia 16 (27.8%), nausea/vomiting 7 (12.3%), and diarrhea 1 (1.8%).
FOLFIRI regimen is effective and well tolerated in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin in Chinese population.
Cancer Chemotherapy and Pharmacology 03/2010; 67(1):147-52. · 2.83 Impact Factor
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Mei Dong,
Feng-Yi Feng,
Yang Zhang,
Guang-Ru Xie,
Ya-Jie Wang,
Ji-Wei Liu,
San-Tai Song,
Qing-Hua Zhou,
Jun Ren,
Shun-Chang Jiao,
Jin Li,
Xiu-Wen Wang,
Qiang Chen,
Zhe-Hai Wang, Nong Xu,
Ji-Feng Feng
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ABSTRACT: To evaluate the efficacy and safety of zoledronic acid in the treatment of bone pain in patients with bone metastasis from solid tumor or multiple myeloma.
A randomized, double-blind, double-simulated and multi-center phase III clinical trail with pamidronate as control was conducted. Patients with moderate to severe bone pain (VAS > 50 mm) induced by solid tumor or multiple myeloma were randomized to receive intravenous zoledronic acid 4 mg or pamidronate 90 mg. Then the change of VAS and urinary NTX/Cr and CTX/Cr were observed in two groups.
From July 2005 to September 2006, 228 patients with bone pain induced by bone metastasis from 15 cancer centers were randomize into two groups: 116 patients in zoledronic acid group and 112 patients in pamidronate group. The VAS value was decreased gradually after treatment in these two groups. Significant improvement in bone pain after treatment were observed both in zoledronic acid group and the control group when compared with baseline VAS on D8 (-11.77% vs. -10.87%), D15 (-24.60% vs. -21.06%) and D28 (-32.37% vs. -31.26%) (P< or =0.0001), but no significant difference existed between two groups (P =0.6587). Compared with baseline, urine NTX/Cr and CTX/Cr level were decreased rapidly after treatment in both groups, the nadir was on D8, the median decreased on D28, which was -36.9% vs. -32.1% for NTX/Cr (P = 0.7922) and -63.2% vs. -47.9% for CTX/Cr (P =0.834). The frequently observed adverse events were pyrexia (19.0% vs. 31.3%), vomiting (6.0% vs. 8.9%), nausea (4.3% vs. 4.5%), fatigue (3.4% vs. 2.7%) and constipation (2.6% vs. 1.8%) in the two groups. Compared with baseline, the serum creatinine level was not significantly increased throughout the study.
Intravenous injection of 4 mg zoledronic acid can significantly reduce bone pain and bone resorption marker in urine in the Chinese patients with bone metastasis from solid tumor or multiple myeloma, which is tolerable and also comparable to pamidronate in the efficacy and safety.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 04/2008; 30(3):215-20.
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Yan Wang,
Jian-Ming Xu,
Lin Shen, Nong Xu,
Jin-Wan Wang,
Shun-Chang Jiao,
Jing-Sheng Zhang,
San-Tai Song,
Jian Li,
Han-Ying Bao,
Lin Yang,
Fang Li
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ABSTRACT: To assess the polymorphism of UGT1A gene in Chinese, and to investigate the correlation between UGT1A polymorphism and irinotecan toxicity in colorectal cancer patients.
70 patients with advanced colorectal cancer were treated with irinotecan and 5-fluorouracil. Polymorphism analysis was performed in all those patients and 100 healthy subjects. Genomic DNA was extracted from peripheral blood and genotyped using polymerase chain reaction and direct sequencing.
14 patients exhibiting grade 3 - 4 neutropenia (20.0%), 16 patients experienced grade 2 - 4 diarrhea (22.9%), including only 4 patients with grade 3 - 4 diarrhea (5.7%). Compared with TA6/7 and TA7/7, UGT1 A1 * 28 wild genotype TA6/6 was significantly associated with reduced toxicity (42.1% vs. 15.7%, P = 0.027). There was no significant difference in the distribution of UGT1A genotypes between colorectal cancer patients and healthy subjects.
Chinese patients exhibit less irinotecan-related diarrhea due to higher frequence of UGT1A A1 * 28 wild genotype TA6/6.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 01/2008; 29(12):913-6.
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ABSTRACT: To evaluate the efficacy and safety of gemcitabine in combination with carboplatin at standard rate or fixed dose rate infusion in patients with advanced non-small-cell lung cancer (NSCLC).
In this prospective study, patients with chemonaive advanced NSCLC were randomized to receive gemcitabine at a standard rate (gemcitabine 1,200 mg/m2 over 30 min, the standard arm) or a fixed dose rate (gemcitabine 1,200 mg/m2 over 120 min, the FDR arm) on days 1 and 8 every 3 week cycle. In both treatment arms, carboplatin at AUC of 5 was administered over 4 h following gemcitabine on day 1 of each cycle.
From November 2003 to June 2005, a total of 42 patients, in which 7 (17%) patients had stage III(B) disease and 35 (83%) had stage IV disease, were enrolled into this study. All patients were included in efficacy and toxicity assessment. No patient had a complete response. Seven (33%) patients in the standard arm and 10 (48%) in the FDR arm had a partial response. The median time to progression and median overall survival time in the standard arm was 5.4 months (95% CI, 3.8-7 months) and 11.5 months (95% CI, 8.2-14.8 months), respectively, while in the FDR arm was 6.5 (95% CI, 4.4-8.6 months) months, 12.0 months (95% CI, 11.3-12.7 months), respectively. The most frequently reported grade 3 or 4 hematological toxicities were thrombocytopenia (38% patients in the standard arm and 43% in the FDR arm) and neutropenia (24% in the standard arm and 33% in the FDR arm). Although hematological toxicity occurred in a little higher percent of patients in the FDR arm than in the standard arm, there were no discernible differences by statistical analysis in both treatment arms (P > 0.05). And significant nonhematologic toxicities were infrequent and tolerable in both arms. No significant difference existed also (P > 0.05).
In this phase II study, gemcitabine in combination with carboplatin either at standard rate or fixed dose rate infusion was clinically effective and well tolerated in patients with advanced NSCLC.
Cancer Chemotherapy and Pharmacology 10/2007; 60(4):601-7. · 2.83 Impact Factor
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ABSTRACT: To evaluate the efficacy and toxicity of leucovorin (LV) plus 5-fluorouracil (5-FU) combined with oxaliplatin every 2 weeks on previously untreated advanced colorectal cancer patients in Chinese population.
Forty-nine patients were enrolled to receive, entirely as inpatients, 2-weekly cycles of oxaliplatin 85 mg/m2 i.v. over 2 hours on Day 1, together with leucovorin 200 mg/m2 over 2 hours, 5-FU 400 mg/m2, bolus, followed by a 22-hours infusion of 5-FU at 600 mg/m2 Days 1-2 (FOLFOX4) every 2 weeks. Treatment was given until progression or unmanageable toxicity. In all, 49 patients received ≥ 1 oxaliplatin dose and a median of 7 treatment cycles (range 1∼27 cycles).
Of the 45 eligible patients, 1 complete response (CR) and 18 partial responses (PRs) were observed for an overall response rate of 42.2 percent (95 percent confidence interval 26∼56 percent). Median progression-free survival was 7.2 months (6.4∼8.0) and median overall survival was 14.8 months (13.1∼16.5). Six patients (12.2 percent) reported Grade 3∼4 neutropenia. Thirty-one patients (62.3 percent) experienced Grade 1∼3 neurotoxicity and only 5 patients (10.2 percent) experienced Grade 3 neurotoxicity.
In our experience, FOLFOX4 regimen is active and well tolerated in patients with previously untreated advanced colorectal cancer in Chinese population.
Cancer Investigation 10/2007; 25(7):599-605. · 1.85 Impact Factor
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ABSTRACT: To investigate the efficacy and relationship between plasma concentrations at the end of infusion (C(end of infusion)) and toxicity profile of fixed-dose-rate gemcitabine plus carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC).
Patients were given gemcitabine by 120 min infusion [at a fixed dose rate (FDR) of 10 mg/m(2)/min] on days 1 and 8 of a 21-day cycle, immediately followed by carboplatin AUC 5 by 4 h infusion on day 1. C (end of infusion) of gemcitabine was determined by ion-pair reversed-phase high-performance liquid chromatography (HPLC).
By the close-out date, in our study population, the estimated median time to tumor progression (TTP) was 7 months (95% CI 4-10 months), median overall survival (OS) was 12 months (95% CI 11.2-12.8 months). The mean value of C (end of infusion) of 21 eligible patients was 16.48 +/- 8.07 micromol/l (range 27.43-2.87 micromol/l). The main hematological toxicities were transient grade 3-4 thrombocytopenia. The mean percentages of reduction of WBC, NEC, PLTC and Hb of 21 eligible patients were 38.3 +/- 38.1%, 31.3 +/- 73.6%, 31.8 +/- 53.5% and 12.0 +/- 12.2%, respectively. The analysis of the C(end of infusion) of gemcitabine and the percentage of reduction in WBC showed a significant correlation (r(2) = 0.4575; p < 0.05). A significant correlation (r(2) = 0.5671; p < 0.05) was also observed between the percentage of reduction of PLTC and C(end of infusion) of gemcitabine infusion.
The clinical data in this trial supports the further evaluation the regimen in advanced NSCLC patients, due to its predictable kinetic behavior and less severe toxicity profile than expected.
Cancer Chemotherapy and Pharmacology 08/2007; 60(2):211-8. · 2.83 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the efficacy and safety of an epirubicin, oxaliplatin and infusional 5-fluorouracil combination in patients with advanced gastric cancer. Patients with previously untreated advanced measurable gastric cancer received epirubicin (50 mg/m2, day 1), oxaliplatin (130 mg/m2 2-h infusion, day 1) and 5-fluorouracil (750 mg/m2, 24-h infusion, day 1-3) every 3 weeks. The primary endpoint of this phase II study was the response rate according to Response Evaluation Criteria in Solid Tumors. Out of 48 patients, 46 were evaluable for efficacy and 48 for toxicity. A median of five cycles (range 1-6) was administered. The overall best response rate was 47.8% (95% confidence interval 33-63%) including 2.2% complete responses and 45.6% partial responses. The median time for progression and median overall survival was 5 (95% confidence interval 4.1-5.9) and 11 months (95% confidence interval 8.1-13.9), respectively. Grade 3/4 neutropenia and leukocytopenia were observed in 25 and 12.5% of patients, respectively. Grade 3/4 nonhematological toxicities included nausea (6.3%), vomiting (14.6%), neurological toxicity (10.4%) and mucositis (2.1%). The epirubicin, oxaliplatin and infusional 5-fluorouracil regimen was effective and well tolerated as a front-line chemotherapy for patients with metastatic or advanced gastric cancer, and should be evaluated further.
Anti-Cancer Drugs 07/2007; 18(5):581-6. · 2.41 Impact Factor
