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1.
Junshik Hong Sae-Won Han Hye Seon Ham Tae-Yong Kim In Sil Choi Byung-Su Kim Do-Youn Oh Seock-Ah Im Gyeong Hoon Kang Yung-Jue Bang Tae-You Kim 《Cancer chemotherapy and pharmacology》2011,67(6):1323-1331
Purpose
To evaluate the efficacy and safety of S-1 in combination with oxaliplatin in a biweekly schedule as first-line treatment in metastatic colorectal cancer and the association between genetic polymorphisms and treatment outcomes.Methods
Eligibility included age 18?C75?years, at least one measurable lesion, no prior chemotherapy except adjuvant chemotherapy, and Eastern Cooperative Oncology Group Performance Status (PS) 0?C2. S-1 40?mg/m2 b.i.d. on days 1?C7 with 85?mg/m2 of oxaliplatin on day 1 was repeated every 2?weeks. Genomic DNA from whole blood was analyzed for 15 single-nucleotide polymorphisms (SNPs) among 8 genes.Results
Fifty-two patients (median age 63?years, range 37?C74) were enrolled: 37 men and 15 women; 44 with a PS of 0 and 8 with a PS of 1; and 41 with initially metastatic cancer and 11 with relapsed disease. Among 51 evaluable patients, objective response rate was 47.1% [95% confidence interval (CI) 32.9?C61.2]. Median follow-up duration was 17.1?months (range 3.9?C28.2?months). Median progression-free survival (PFS) was 6.4?months (95% CI 4.8?C8.1), and median overall survival had not been reached yet. Reported grade 3 toxicities were neutropenia (7.7%), thrombocytopenia (5.8%), sensory neuropathy (7.7%) and diarrhea (1.9%). There was no grade 4 toxicity or neutropenic fever. Patients with A/G or G/G genotype in GSTP1 Ile105Val SNP had longer PFS than patients with A/A (median 8.3 vs. 6.1?months, P?=?0.04).Conclusions
Biweekly S-1 with oxaliplatin is effective and has improved tolerability and convenience compared to other fluoropyrimidine with oxaliplatin combinations. GSTP1 Ile105Val SNP is associated with treatment outcomes. 相似文献2.
Byung Woog Kang Ji Yun Jeong Yee Soo Chae Soo Jung Lee Yoo Jin Lee Jun Young Choi In-Kyu Lee Seong Woo Jeon Han Ik Bae Da Keun Lee Oh-kyoung Kwon Ho Young Chung Wansik Yu Jong Gwang Kim 《Cancer chemotherapy and pharmacology》2012,70(5):735-741
Purpose
The present study analyzed the expression of phosphorylated AMP-activated protein kinase (pAMPK), Fyn kinase, and pyruvate dehydrogenase kinase-1 (PDK-1) and their impact on the survival of patients with resected gastric cancer who received cisplatin-based adjuvant chemotherapy.Patients and methods
Korean patients with stage II–IV (M0) gastric adenocarcinoma who underwent a gastrectomy with D2 lymph node resection and received a combination regimen of cisplatin and S-1 were enrolled. Immunohistochemistry was carried out to determine the expression of pAMPK, Fyn kinase, and PDK-1 in operative specimens of gastric cancer. The expression was divided into two groups according to the intensity score (negative: 0 or 1+ and positive: 2+ or 3+).Results
From January 2006 to July 2010, 73 tumor samples obtained from 74 patients were analyzed. Forty patients were included in the pAMPK-positive group, while 33 patients were included in the pAMPK-negative group. Meanwhile, positive Fyn kinase expression was observed in only 10 patients (13.7?%), and there was no or very weak PDK-1 staining. The clinicopathologic characteristics were similar between the two groups according to the expression of pAMPK. With a median follow-up duration of 26.5?months (2.6–73.2), the estimated 3-year relapse-free survival (RFS) and overall survival rates were 55.0 and 78.4?%, respectively. In a multivariate analysis adjusted for age, sex, Lauren classification, and stage, the pAMPK-negative group was significantly associated with improved RFS (Hazard ratio?=?0.459, 95?% CI 0.109–0.711, P?=?0.043).Conclusion
A low expression of pAMPK was found to be correlated with better RFS in patients with resected gastric cancer treated with adjuvant cisplatin-based chemotherapy. 相似文献3.
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 《Cancer chemotherapy and pharmacology》2011,67(1):147-152
Purpose
To evaluate the efficacy and safety of FOLFIRI regimen in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.Methods
The FOLFIRI regimen consisted of intravenous infusion of irinotecan 180?mg/m2 on day 1 plus leucovorin (LV) 400?mg/m2 on day 1 plus 5-fluorouracil (5-FU) 400?mg/m2 bolus on day 1 plus 46-hour intravenous infusion of 5-FU 2,400?mg/m2, every 2?weeks as one cycle. The main selection criterion for this study was the advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.Results
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?C5.7?months), and median overall survival was 7.8?months (95% CI 13.1?C16.5?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%).Conclusion
FOLFIRI regimen is effective and well tolerated in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin in Chinese population. 相似文献4.
Shitara K Morita S Fujitani K Kadowaki S Takiguchi N Hirabayashi N Takahashi M Takagi M Tokunaga Y Fukushima R Munakata Y Nishikawa K Takagane A Tanaka T Sekishita Y Sakamoto J Tsuburaya A 《Gastric cancer》2012,15(3):245-251
Background
It is unclear whether S-1 plus cisplatin is effective for patients with recurrent gastric cancer after adjuvant S-1 chemotherapy.Methods
We retrospectively evaluated the efficacy of S-1 plus cisplatin in patients whose gastric cancer recurred after adjuvant S-1 chemotherapy.Results
In the 52 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 8.1?months, and the median recurrence-free interval (RFI) since the last administration of adjuvant S-1 was 6.4?months. Among the 36 patients with measurable lesions, 7 achieved a complete or partial response, and 13 were evaluated as having stable disease, for an overall response rate of 19.4% and a disease control rate of 55.6%. For all patients, the median progression-free survival (PFS) was 4.8?months, and the median overall survival (OS) was 12.2?months. Compared with patients with an RFI of <6?months (n?=?25), patients with an RFI of ≥6?months (n?=?27) had a significantly higher response rate (5.0 vs. 37.5%, respectively), longer PFS (2.3 vs. 6.2?months, respectively), and longer overall survival (7.3 vs. 16.6?months, respectively). According to a multivariate Cox model including performance status (PS) and reason for discontinuation of adjuvant S-1, an RFI of 6?months was still significantly associated with PFS and OS.Conclusions
S-1 plus cisplatin is effective for patients with gastric cancer that recurs after adjuvant S-1 chemotherapy, especially for those with an RFI of ≥6?months. 相似文献5.
Background
Cetuximab, a monoclonal antibody against the epidermal growth factor receptor, inconsistently improves response rates (RR), progression-free survival (PFS) and overall survival (OS) in the first-line treatment of advanced colorectal cancer patients with K-ras wild-type (WT) tumors.Methods
We performed a meta-analysis of four trials where K-ras WT Pts received a fluoropyrimidine (infusional vs. bolus 5-fluorouracil (5-FU) vs. capecitabine) and oxaliplatin or irinotecan with and without cetuximab (CRYSTAL, OPUS, COIN and NORDIC VII trials) and two trials, where K-ras WT and mutant patients received cetuximab and a fluoropyrimidine (capecitabine in a German AIO study and infusional 5-FU in the CECOG study) with oxaliplatin versus irinotecan. We sought to determine whether the choice of fluoropyrimidine or of oxaliplatin versus irinotecan affects the response to cetuximab. Meta-analysis was performed in the context of a mixed effects model with a random effect for each study.Results
Only patients treated with infusional 5-FU-based chemotherapy derived benefit from cetuximab. Relative to infusional 5-FU, patients treated with capecitabine/bolus 5-FU-based doublet chemotherapy had a 42?% (95?% CI 21?C58?%; p?0.001) decrease in response probability and a 52?% (95?% CI 20?C93?%; p?0.001) and 33?% (95?% CI 7?C65?%; p?=?0.012) increase, respectively, in risk of progression and death. The choice of oxaliplatin or irinotecan did not affect benefit from cetuximab.Conclusion
The lack of benefit for cetuximab with capecitabine/bolus 5-FU regimens is unexpected. Cetuximab should only be used with infusional 5-FU regimens in the first-line treatment of K-ras WT colorectal cancer patients. Further study is urgently needed to elucidate the basis of this observation. 相似文献6.
Sara De Dosso Elena Zanellato Martina Nucifora Renzo Boldorini Angelica Sonzogni Roberto Biffi Nicola Fazio Eraldo Bucci Ottavio Beretta Stefano Crippa Piercarlo Saletti Milo Frattini 《Cancer chemotherapy and pharmacology》2013,72(1):159-165
Background
Adjuvant chemotherapy is gaining an increasing role in resectable gastric cancer. Customizing chemotherapy on the basis of chemosensitivity may improve outcome, and putative predictive molecular markers have been mostly evaluated in Asian patients. We profiled key DNA and damage signaling factors and correlated them with outcome, in a European cohort.Methods
Formalin-fixed tumor samples obtained from surgical specimens of patients treated with adjuvant cisplatin-based chemotherapy for gastric cancer were analyzed. Immunohistochemistry (IHC) was performed to analyze excision repair cross-complementing gene 1 (ERCC1) and thymidylate synthase (TS) expression, and p53 mutations were detected with direct sequencing.Results
Among the 68 patient recruited, the median age was 69 (range 30–74), and UICC stage was III in 44 patients (65 %). With a median follow-up of 40.5 months, disease-free and overall survival were 18.0 (95 % CI 13.4–22.76) and 56 months (95 % CI 44.87–67.13), respectively. ERCC1 score was 0 in 14 out 67 (21 %) cases, 1 in 19 (28 %), 2 in 20 (30 %) and 3 in 14 cases (21 %). Longer overall survival (p = 0.04) was found in patients categorized as ERCC1 negative by IHC according to median score. TS score was 0 in 16 out 67 (24 %) cases, 1 in 27 (40 %), 2 in 16 (24 %) and 3 in 8 cases (12 %). Mutations of p53 were found in 21 out 66 (32 %) cases. Neither TS nor p53 were found to correlate with outcome.Conclusion
Excision repair cross-complementing gene 1 by IHC might predict patients more likely to benefit from adjuvant cisplatin-based chemotherapy in curatively resected gastric cancer. In patients exhibiting ERCC1 positive tumors, alternative regimens should be evaluated. 相似文献7.
Renata D’Alpino Peixoto Aalok Kumar Howard John Lim 《Journal of gastrointestinal oncology.》2015,6(5):487-491
Background
Little is known regarding the efficacy of oxaliplatin-based chemotherapy for metastatic colon cancer patients who have already received adjuvant oxaliplatin-based chemotherapy.Methods
We retrospectively reviewed 22 consecutive patients who developed recurrence after adjuvant oxaliplatin-based chemotherapy for stage III colon cancer and received another course of oxaliplatin-based chemotherapy for their metastatic disease. The main endpoint was progression-free survival (PFS).Results
A total of 635 patients received oxaliplatin-based chemotherapy for stage III colon cancer at the British Columbia Cancer Agency from 2006 to 2011. A total of 176 patients recurred, 22 (12.5%) of whom were re-exposed to oxaliplatin in the metastatic scenario. Oxaliplatin in combination with fluoropyrimidine was given as first, second and third line in in 3 (13.6%), 14 (63.6%), and 5 (22.7%) patients respectively. Median time from the last cycle of adjuvant oxaliplatin-based chemotherapy to the first cycle of palliative oxaliplatin-based chemotherapy was 44.3 months. Median PFS and overall survival (OS) were 3.3 (95% CI, 1.4-5.1) and 10.0 months (95% CI, 5.3-14.6), respectively. There was no difference in PFS for patients re-exposed to oxaliplatin less than 36 months compared to longer (3.6 versus 3.1 months, P=0.793, HR =0.88).Conclusions
In this population-based study, only a small proportion of pts who recurred after oxaliplatin-based adjuvant therapy received oxaliplatin in the metastatic setting. Re-exposure of oxaliplatin in combination with fluoropyrimidine is associated with only modest PFS benefit. Larger studies evaluating the role of oxaliplatin re-exposure are needed. 相似文献8.
T. Waddell S. Gollins W. Soe J. Valle J. Allen D. Bentley J. Morris A. Lloyd R. Swindell M. B. Taylor M. P. Saunders 《Cancer chemotherapy and pharmacology》2011,67(5):1111-1117
Purpose
To evaluate the efficacy, safety and quality of life of a short course of oxaliplatin plus capecitabine (XELOX) followed by single-agent capecitabine in patients with previously untreated, inoperable, metastatic colorectal cancer.Methods
Patients received intravenous oxaliplatin 130?mg/m2 on d1 plus oral capecitabine 1,000?mg/m2 twice daily (bid) on d1?C14 every 21?days for four cycles. Patients achieving stable disease (SD) or better than received capecitabine 1,250?mg/m2 bid on d1?C14 every 21?days until disease progression. The primary endpoint was progression-free survival (PFS).Results
Overall, 21/45 (47%) of patients responded to the initial XELOX chemotherapy whilst SD or better was documented in 76%. Median PFS was 6.7 (95% CI 5.7?C9.6) months, and median overall survival (OS) was 20.5 (95% CI 13.1?C28.1) months. In the 34 patients who then received capecitabine maintenance therapy, the median PFS was 8.1 (95% CI 6.2?C11.8) months and median OS was 23.1 (95% CI 17.8?C28.5) months. A marked reduction in the vast majority of all grades of adverse event occurred on switching from initial XELOX to maintenance capecitabine chemotherapy including grades 1?C2 (77 vs. 47%) and grade 3 (7 vs. 3%) neuropathy, diarrhoea and lethargy.Conclusions
Short-course XELOX followed by capecitabine maintenance therapy provides an active and well-tolerated treatment option for patients with previously untreated metastatic colorectal cancer. A median OS of more than 20?months is promising and by limiting the number of oxaliplatin infusions, this approach minimises the risk of unwanted cumulative neurotoxicity, is cheaper and more convenient for both patients and healthcare providers. 相似文献9.
Context
In the metastatic setting treatment goals are palliative. Chemotherapy can prolong survival, improve symptoms and can help to maintain a better quality of life.Objective
The aim of this study was to discuss the new treatment options and the existing results in advanced gastric cancer.Material and methods
Treatment recommendations are given in consideration of updated literature (Pubmed, MEDLINE and manual search).Results
Combination chemotherapy including a platinum compound and a fluoropyrimidine are regarded as the gold standard of care. Oxaliplatin can substitute for cisplatin while capecitabine or S1 can substitute for infusional 5-FU. In elderly patients oxaliplatin has advantages compared with cisplatin. Triplet combinations containing a platinum salt, a fluoropyrimidine and a taxane or (with less evidence) an anthracycline are more efficacious but also expose patients to more side effects. Second line chemotherapy is indicated for patients who progress during or after first line chemotherapy. The monoclonal antibody trastuzumab has been shown to prolong survival when combined with cisplatin and 5-FU or capecitabine in gastric cancer patients with overexpression of the growth factor HER2.Conclusion
The therapeutic options for advanced gastric cancer have significantly increased. Presently, there are several effective treatment regimens available. 相似文献10.
Kazuhiro Nishikawa Akira Tsuburaya Takaki Yoshikawa Masazumi Takahashi Kazuaki Tanabe Kensei Yamaguchi Shigefumi Yoshino Tsutomu Namikawa Toru Aoyama Yasushi Rino Junji Kawada Akihito Tsuji Koichi Taira Yutaka Kimura Yasuhiro Kodera Yoshinori Hirashima Hiroshi Yabusaki Naoki Hirabayashi Kazumasa Fujitani Yumi Miyashita Satoshi Morita Junichi Sakamoto 《Gastric cancer》2018,21(5):811-818
Backgrounds
In Japan, standard regimens for advanced gastric cancer (AGC) include S-1 chemotherapy. The standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine alone is platinum-based chemotherapy, while the standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine plus platinum is second-line chemotherapy. To evaluate the efficacy and safety of capecitabine plus cisplatin (XP) treatment for AGC patients who relapse within 6 months after S-1-based therapy, we conducted a multicenter phase II trial (NCT01412294).Methods
HER2-negative gastric cancer patients treated with adjuvant chemotherapy including S-1 for more than 12 weeks and relapsed within 6 months were treated with capecitabine 1000 mg/m2 bid for 14 days plus cisplatin 80 mg/m2 on day 1 of a 3-week cycle. The primary endpoint was PFS; secondary endpoints were OS, time to treatment failure, overall response rate (ORR) and safety.Results
Forty patients (median age 64) were enrolled; of those, 37 (92.5%) received adjuvant S-1 monotherapy. Median PFS was 4.4 months (95% CI 3.6–5.1), which was longer than the 2-month protocol-specified threshold (p < 0.001). Median OS was 13.7 months (95% CI 9.0–17.7) and ORR was 8/30 (26.7%) (95% CI 14.2–44.4). Most common grade ≥ 3 adverse events were neutropenia (23%), anemia (18%), elevated serum creatinine (18%), fatigue (13%), diarrhea (7.5%), and anorexia (7.5%).Conclusions
XP was safe and effective in patients with early relapse after S-1 adjuvant chemotherapy for curatively resected gastric cancers. XP may be a good option for the treatment of patients after early failure after adjuvant S-1.Trial registration
NCT01412294.11.
Sook Ryun Park Myeong-Cherl Kook Il Ju Choi Chan Gyoo Kim Jong Yeul Lee Soo-Jeong Cho Young-Woo Kim Keun Won Ryu Jun Ho Lee Jong Seok Lee Young-Iee Park Noe Kyeong Kim 《Cancer chemotherapy and pharmacology》2010,65(3):579-587
Purpose
We performed a retrospective study to evaluate the efficacy of cetuximab plus chemotherapy in metastatic gastric cancer (MGC) patients previously treated with chemotherapy and to investigate potential predictors of treatment efficacy in those patients.Methods
Thirty-two patients with MGC were included in this study. Cetuximab was delivered, often combined with irinotecan-based chemotherapy. Thirty patients were analyzed for K-ras mutations via direct sequencing of the tumor DNA.Results
Patients were heavily pretreated with a median number of three previous lines of palliative chemotherapy (56% of the patients were refractory to all of the following drugs: fluoropyrimidines, cisplatin, irinotecan, oxaliplatin, and docetaxel) and 53% of the patients displayed poor performance status. Of 28 response-assessable patients, the overall response rate to cetuximab plus chemotherapy was 3.6% [95% confidence interval (CI) 0–10.5%] and the disease control rate was 28.6%. The median progression-free survival (PFS) was 1.7 months (95% CI 1.3–2.1 months), and the median overall survival (OS) was 3.2 months (95% CI 1.4–5.0 months). Multivariate analyses revealed that skin rash and performance status were significantly associated with PFS and OS. The presence of a K-ras mutation (13.3%) was not associated with either PFS or OS.Conclusion
Our study suggests that MGC patients with good performance status and skin rash benefit most from salvage cetuximab combined with chemotherapy, even in heavily pretreated status. 相似文献12.
Joung-Soon Jang Ho Yeong Lim In Gyu Hwang Hong Suk Song NaeChoon Yoo SoYoung Yoon Yeul Hong Kim Eunsik Park Jae Ho Byun Myung Ah Lee Suk Joong Oh Kyung Hee Lee Bong Seog Kim Sang Cheul Oh Sam Yong Kim Sang Jae Lee 《Cancer chemotherapy and pharmacology》2010,65(4):641-647
Purpose
Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months in patients with biliary tract cancers (BTCs). The aim of this study was to evaluate the efficacy and safety of the combination chemotherapy with gemcitabine and oxaliplatin (GEMOX) in patients with BTCs including gall bladder cancer.Methods
We carried out a nationwide multicenter phase II study evaluated the efficacy and safety of GEMOX as first-line therapy in patients with advanced BTCs. Eligible patients with previously untreated locally advanced or metastatic BTCs received gemcitabine 1,000 mg/m2 (day 1 and 8) and oxaliplatin 100 mg/m2 (day 1), every 3 weeks.Results
Fifty-three patients were evaluated, 60% had cholangiocarcinoma and the remaining 40% gall bladder cancer; the objective response rate was 18.9% (10/53 patients including 1 Complete response) [14.9%; 95% confidence interval (CI), 7.4–25.7%] in the treated population. Stable disease were observed in 27/53 (50.9%) patients, disease control rate was achieved in 69.8% of all patients. Median progression-free survival was 4.8 months (3.1–6.5, 95% CI) and median overall survival was 8.3 months (5.8–10.8, 95% CI). Grade 3/4 toxicities included neutropenia (33.9% of patients) and thrombocytopenia (7.6%).Conclusions
The GEMOX regimen demonstrated a modest antitumor activity and is well tolerated in patients with advanced BTCs. 相似文献13.
Naminatsu Takahara Hiroyuki Isayama Yousuke Nakai Takashi Sasaki Tsuyoshi Hamada Rie Uchino Suguru Mizuno Koji Miyabayashi Hirofumi Kogure Natsuyo Yamamoto Naoki Sasahira Kenji Hirano Hideaki Ijichi Keisuke Tateishi Minoru Tada Kazuhiko Koike 《Cancer chemotherapy and pharmacology》2013,72(5):985-990
Purpose
The aim of this study was to evaluate S-1 and oxaliplatin combination chemotherapy (SOX) in patients with refractory pancreatic cancer (PC).Methods
Consecutive patients with advanced PC refractory to gemcitabine who were treated with oral S-1 (80 mg/m2) on days 1–14 and intravenous oxaliplatin (100 mg/m2) on day 1 every 3 weeks were studied retrospectively. The primary end point was the objective response rate (ORR). The secondary end points were progression-free survival (PFS), overall survival (OS), the disease control rate (DCR), and safety.Results
Between March 2009 and October 2011, 30 patients were treated with SOX, with a median of two courses (range 1–8). The ORR and DCR were 10.0 and 50.0 %, respectively. Median PFS and OS were 3.4 months (95 % confidence interval [CI] 1.3–5.3) and 5.0 months (95 % CI 3.4–7.4), respectively. The median PFS and OS were 5.6 and 9.1 months in patients receiving S-1 and oxaliplatin as a second-line treatment. Major grade 3 or 4 adverse events included neutropenia (10.0 %), anemia (3.3 %), and diarrhea (6.7 %).Conclusions
SOX was well tolerated and moderately effective in patients with refractory PC. 相似文献14.
Koo DH Ryu MH Ryoo BY Lee SS Moon JH Chang HM Lee JL Kim TW Kang YK 《Gastric cancer》2012,15(3):305-312
Background
Doses and schedules of the combination of S-1 and cisplatin for the treatment of advanced gastric cancer (AGC) have not been standardized. We therefore evaluated the efficacy and feasibility of a 3-week schedule of S-1 and cisplatin in patients with AGC, as well as assessing factors prognostic of patient outcomes.Methods
A total of 159 patients with AGC were treated with S-1 (40?mg/m2 bid on days?1–14) and cisplatin (60?mg/m2 IV on day?1) between January 2004 and December 2008.Results
Median follow-up duration was 20.0?months (range, 11.4–48.5?months), during which time 129 patients (81.1%) died. Patients received a median 6 cycles of chemotherapy (range, 1–19 cycles). Among the 59 patients with measurable disease, 1 achieved a complete response (1.7%) and 24 (40.7%) had partial responses, giving an overall response rate of 42.4% (95% CI, 23.0–61.8%). The median progression-free survival (PFS) was 5.8?months (95% CI, 4.8–6.9?months), and the median overall survival (OS) was 11.3?months (95% CI, 9.6–13.0?months). Multivariate analysis showed that initial metastasis, bone metastasis, and liver metastasis were independent prognostic factors for reduced PFS, whereas poor performance status, initial metastasis, and bone metastasis were prognostic for reduced OS. Application of a previous prognostic model showed that observed PFS and OS survival curves for patients in various risk groups differed significantly (P?0.001 each).Conclusions
A 3-week regimen of S-1 plus cisplatin was active and well tolerated as first-line treatment in patients with AGC. Disease status and bone metastasis were the most important prognostic factors. 相似文献15.
Yoon-Koo Kang Jeong Hwan Yook Heung-Moon Chang Min-Hee Ryu Changhoon Yoo Dae Young Zang Jae-Lyun Lee Tae Won Kim Dae Hyun Yang Se Jin Jang Young Soo Park Young Jack Lee Hwoon-Yong Jung Jin-Ho Kim Byung Sik Kim 《Cancer chemotherapy and pharmacology》2014,73(1):139-149
Purpose
To improve the efficacy of adjuvant chemotherapy with mitomycin-C and fluoropyrimidine (Mf) in gastric cancer, we designed a new regimen (iceMFP) and investigated in a phase III study.Methods
We randomly assigned 640 patients with resectable and macroscopically recognizable serosa-invading gastric cancer to Mf or iceMFP group during operation. The Mf consisted of intravenous mitomycin-C (20 mg/m2) at 3–6 weeks after surgery and oral doxifluridine (460–600 mg/m2/day) starting 4 weeks after the administration of mitomycin-C and continuing for 3 months. The iceMFP consisted of intraoperative intraperitoneal cisplatin (100 mg), intravenous mitomycin-C (15 mg/m2) on postoperative day 1, followed by oral doxifluridine for 12 months, and six monthly intravenous cisplatin (60 mg/m2). The primary endpoint was 3-year recurrence-free survival (RFS).Results
A total of 521 patients (258 in Mf, 263 in iceMFP) were eligible for analysis after excluding patients with stage I disease, distant metastasis, or R1 resection. With a median follow-up of 3.5 years, the iceMFP group had a higher RFS (hazard ratio [HR] 0.70; 95 % confidence interval [CI] 0.54–0.90; p = 0.006; 3-year RFS 60 % vs. 50 %) and overall survival (HR 0.71; 95 % CI 0.53–0.95; p = 0.02; 3-year overall survival, 71 vs. 60 %) compared with the Mf group. This was confirmed at extension analysis after a median 6.6 years of follow-up. Both regimens were well tolerated with no differences in surgical complications.Conclusion
The efficacy of adjuvant Mf was significantly improved by the additional therapeutic strategies of iceMFP. Considering negative results of AMC0201, these suggest that early initiation of chemotherapy and/or intraperitoneal cisplatin played a distinct role in the improved efficacy. 相似文献16.
Ando T Hosokawa A Kajiura S Itaya Y Ueda A Fujinami H Nishikawa J Kobayashi T Horikawa N Tsukioka Y Yabushita K Note M Ogawa K Sugiyama T 《Gastric cancer》2012,15(4):427-432
Background
Only partial cross-resistance between docetaxel and paclitaxel has been demonstrated in breast and ovarian cancers. Whether weekly paclitaxel is effective in patients with advanced gastric cancer refractory to docetaxel-based chemotherapy remains unclear, and we aimed to clarify the efficacy and safety of weekly paclitaxel in such patients.Methods
Patients who had received docetaxel-based regimens were assigned to the prior-docetaxel group, and those who had never received docetaxel were designated as the non-docetaxel group. Paclitaxel at 80?mg/m2 was administered by intravenous infusion in all patients, and this was repeated weekly for 3?weeks out of 4.Results
Between April 2006 and June 2011, 65 patients were studied: 26 in the prior-docetaxel group and 39 patients were non-docetaxel group. The median age, gender, performance status, histological type, history of gastrectomy, and the locations and numbers of metastatic sites did not differ significantly between the two groups. In the prior-docetaxel group, the response rate (RR) was 14.2% (3/21) among patients with measurable lesions, median progression-free survival (PFS) was 79?days [95% confidence interval (CI), 47–135?days], and overall survival (OS) was 123?days (95% CI, 90–215?days) from the initiation of paclitaxel treatment. In the non-docetaxel group, the RR was 11.5% (3/26) among patients with measurable lesions, PFS was 82?days (95% CI, 52–106?days), and OS was 143?days (95% CI, 121–178?days). The efficacy of weekly paclitaxel thus appeared to be similar in the two groups.Conclusions
Weekly paclitaxel was modestly active in patients with gastric cancer refractory to docetaxel-based chemotherapy. 相似文献17.
Chikara Kunisaki Masazumi Takahashi Hirochika Makino Takashi Oshima Shoichi Fujii Ryo Takagawa Jun Kimura Takashi Kosaka Hidetaka A. Ono Hirotoshi Akiyama Kunio Kameda Fumihiko Kito Satoshi Morita Itaru Endo 《Cancer chemotherapy and pharmacology》2011,67(6):1363-1368
Purpose
We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel combination therapy in patients with advanced gastric cancer.Methods
Patients with histologically proven, unresectable advanced or recurrent gastric cancer, a performance status (PS) of 0?C2 and no prior chemotherapy history were eligible for inclusion (n?=?45). Patients received a total of 215 treatment courses (median, 4; range, 2?C12) of S-1 oral administration twice daily for 1?week followed by a drug-free interval of 1?week. Docetaxel (40?mg/m2) was administered intravenously on days 1 and 15.Results
We observed 25 partial responses (55.6%) and one complete response (2.2%), resulting in an overall response rate of 57.8%. Twenty-four patients (53.3%) received second-line chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of the study. The median overall survival time was 15.3?months, the median time to progression was 6.9?months, and the median duration of response in 26 patients was 8.0?months. Neutropenia was the most frequently observed (40.4%) haematological toxicity at grades 3 and 4 and leucopenia was the second most common (29.8%). There were no treatment-related deaths.Conclusions
S-1 plus docetaxel combination therapy in an outpatient setting provided promising activity with acceptable adverse toxicities. 相似文献18.
Inkeun Park Min-Hee Ryu Yoon Hee Choi Hyo Jeong Kang Jeong Hwan Yook Young Soo Park Hyun Jin Kim Hwoon-Yong Jung Gin Hyug Lee Kab Choong Kim Byung Sik Kim Yoon-Koo Kang 《Cancer chemotherapy and pharmacology》2013,72(4):815-823
Purpose
Adjuvant chemotherapy trial of TS-1 for gastric cancer study demonstrated that postoperative S-1 chemotherapy for 1 year improved overall survival of locally advanced gastric cancer (LAGC) patients. The goals of this study were to evaluate the feasibility and efficacy of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy followed by surgery and adjuvant S-1 chemotherapy.Methods
In this single-center, open-label, phase II study, patients with potentially resectable adenocarcinoma of the stomach or gastroesophageal junction were eligible. For neoadjuvant chemotherapy, docetaxel 50 mg/m2 on day (D) 1, oxaliplatin 100 mg/m2 on D1, and S-1 40 mg/m2 bid orally on D1–14 were administrated every 3 weeks for three cycles. After DOS chemotherapy, gastrectomy was performed, and then, adjuvant S-1 40 mg/m2 bid was given on D1–28 every 6 weeks for 1 year. The primary endpoints were the proportion of patients who did not experience grade 3 or 4 toxicities (except grade 3 neutropenia) and R0 resection rates.Results
A total of 41 patients were enrolled. All patients completed three planned cycles of neoadjuvant chemotherapy without disease progression. Eighteen patients (43.9 %) did not experience any grade 3–4 toxicity (except grade 3 neutropenia) during the neoadjuvant chemotherapy. All patients underwent surgery, and R0 resection was achieved in 40 patients (97.6 %).Conclusion
Neoadjuvant DOS chemotherapy could be performed safely with a high R0 resection rate in LAGC patients. A phase III trial is currently underway. 相似文献19.
Díaz Beveridge R Aparicio J Tormo A Estevan R Artes J Giménez A Segura á Roldán S Palasí R Ramos D 《Clinical & translational oncology》2012,14(6):471-480
Introduction
Neoadjuvant 5-FU-based chemoradiotherapy in resectable rectal cancer (RC) is a standard of treatment. The use of oral fluoropyrimidines and new agents such as oxaliplatin may improve efficacy and tolerance.Material and methods
Between 1999 and 2009, 126 RC patients with T3?CT4 and/or N+ disease were given three successive protocols: UFT (32), UFT-oxaliplatin (75) and capecitabine-oxaliplatin (19), alongside 45 Gy of radiotherapy; with surgery 4?C6 weeks after. Adjuvant treatment was given in all patients. The primary objective was pathologic complete response (pCR).Results
Preoperative therapy was well tolerated, with no toxic deaths and a 15% grade 3?C4 toxicity rate. Eighty-five percent of patients received the full chemotherapy dose, 56% had an abdominoperineal resection, 6% reinterventions and 57% received the full adjuvant chemotherapy planned. The pCR rate was 13%. The downstaging rate was 80%; 8% had progression of disease. The relapse rate was 20%, with local relapse in 6%. By 5 years of followup, 92% of relapses had occurred. Median follow-up was 73 months, 5- and 10-year disease-free survival rates were 75% and 50%, and 5- and 10-year overall survival rates were 79% and 66% respectively. There was no benefit from the use of oxaliplatin regarding survival or pCR rates. Older patients had worse long-term outcomes.Conclusions
Neoadjuvant chemoradiotherapy with oral fluoropyrimidines and oxaliplatin is feasible and well tolerated. The risk of early progression is low. However, there was no added benefit with the use of oxaliplatin. There were no relapses in patients with pCR. The role of adjuvant chemotherapy is unclear. 相似文献20.
Shahid Ahmed Nayyer Iqbal Sunil Yadav Adnan Zaidi Osama Ahmed Riaz Alvi Donald Gardner Kamal Haider 《Journal of gastrointestinal cancer》2014,45(3):284-290