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1.
Schott AF Barlow WE Albain KS Chew HK Wade JL Lanier KS Lew DL Hayes DF Gralow JR Livingston RB Hortobagyi GN 《The oncologist》2012,17(2):179-187
Background.
Interest in oral agents for the treatment of metastatic breast cancer (MBC) has increased because many patients prefer oral to i.v. regimens. We evaluated a simple oral combination of capecitabine with cyclophosphamide (CPA) for MBC.Methods.
The trial was designed to determine whether or not combination therapy would achieve a 42% response rate (RR) using the Response Evaluation Criteria in Solid Tumors (RECIST) in MBC. Patients with two or fewer prior chemotherapy regimens for MBC were eligible. Those with estrogen receptor–positive MBC had to have progressed on endocrine therapy. Patients had measurable disease or elevated mucin (MUC)-1 antigen and received CPA, 100 mg daily on days 1–14, and capecitabine, 1,500 mg twice daily on days 8–21, in 21-day cycles.Results.
In 96 eligible patients, the median progression-free survival (PFS) interval was 5.9 months (95% confidence interval [CI], 3.7–8.0 months) and median overall survival (OS) time was 18.8 months (95% CI, 13.1–22.0 months). The RR was 36% (95% CI, 26%–48%) in 80 patients with measurable disease. The MUC-1 antigen RR was 33% (95% CI, 20%–48%), occurring in 15 of 46 patients with elevated MUC-1 antigen. Toxicity was mild, with no treatment-related deaths.Conclusions.
PFS, OS, and RR outcomes with capecitabine plus CPA compare favorably with those of capecitabine monotherapy and combination therapy with bevacizumab, sorafenib, or ixabepilone. The addition of these other agents to capecitabine does not improve OS time in MBC patients, and this single-arm study does not suggest that the addition of CPA to capecitabine has this potential in an unselected MBC population. When OS prolongation is the goal, clinicians should choose single-agent capecitabine. 相似文献2.
David Cameron Michelle Casey Cristina Oliva Beth Newstat Bradley Imwalle Charles E. Geyer 《The oncologist》2010,15(9):924-934
Objectives.
A planned interim analysis of study EGF100151 prompted early termination of enrollment based on a longer time to progression with lapatinib and capecitabine than with capecitabine alone in patients with human epidermal growth factor receptor (HER)-2+ previously treated advanced breast cancer or metastatic breast cancer (MBC). Here, we report final analyses of overall survival.Patients and Methods.
Women with HER-2+ MBC who progressed after regimens that included, but were not limited to, anthracyclines, taxanes, and trastuzumab, were randomized to lapatinib (1,250 mg/day) plus capecitabine (2,000 mg/m2) or capecitabine monotherapy (2,500 mg/m2) on days 1–14 of a 21-day cycle.Results.
At enrollment termination, 399 patients were randomized, and nine were being screened and were offered combination treatment. In total, 207 and 201 patients were enrolled to combination therapy and monotherapy, respectively. Thirty-six patients receiving monotherapy crossed over to combination therapy following enrollment termination. The median overall survival times were 75.0 weeks for the combination arm and 64.7 weeks for the monotherapy arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.71–1.08; p = .210). A Cox regression analysis considering crossover as a time-dependent covariate suggested a 20% lower risk for death for patients treated with combination therapy (HR, 0.80; 95% CI, 0.64–0.99; p = .043). The low incidence of serious adverse events was consistent with previously reported rates.Conclusions.
Although premature enrollment termination and subsequent crossover resulted in insufficient power to detect differences in overall survival, exploratory analyses demonstrate a trend toward a survival advantage with lapatinib plus capecitabine. These data continue to support the efficacy of lapatinib in patients with HER-2+ MBC. 相似文献3.
PG Corrie R Bulusu CB Wilson G Armstrong S Bond R Hardy S Lao-Sirieix D Parashar A Ahmad F Daniel M Hill G Wilson C Blesing AM Moody K McAdam M Osborne 《British journal of cancer》2012,107(4):585-587
Background:
Pyridoxine is frequently used to treat capecitabine-induced hand–foot syndrome (HFS), although the evidence of benefit is lacking. We performed a randomised placebo-controlled trial to determine whether pyridoxine could avoid the need for capecitabine dose modifications and improve outcomes.Methods:
A total of 106 patients planned for palliative single-agent capecitabine (53 in each arm, 65%/ 35% colorectal/breast cancer) were randomised to receive either concomitant pyridoxine (50 mg po) or matching placebo three times daily.Results:
Compared with placebo, pyridoxine use was associated with an increased rate of avoiding capecitabine dose modifications (37% vs 23%, relative risk 0.59, 95% CI 0.29, 1.20, P=0.15) and fewer grade 3/4 HFS-related adverse events (9% vs 17%, odds ratio 0.51, 95% CI 0.15–1.6, P=0.26). Use of pyridoxine did not improve response rate or progression-free survival.Conclusion:
Pyridoxine may reduce the need for capecitabine dose modifications and the incidence of severe HFS, but does not impact on antitumour effect. 相似文献4.
N Tubiana-Mathieu P Bougnoux D Becquart A Chan P-F Conte F Majois M Espie M Morand N Vaissiere G Villanova 《British journal of cancer》2009,101(2):232-237
Background:
This multicentre, international phase II trial evaluated the efficacy and safety profile of a first-line combination of oral vinorelbine plus capecitabine for women with metastatic breast cancer (MBC).Methods:
Patients with measurable, HER2-negative disease received, as a first line in metastatic setting, 3-weekly cycles of oral vinorelbine 80 mg m−2 (after a first cycle at 60) on day 1 and day 8, plus capecitabine 1000 mg m−2 (750 if ⩾65 years of age) twice daily, on days 1–14. Treatment was continued until progression or unacceptable toxicity.Results:
A total of 55 patients were enrolled and 54 were treated (median age: 58.5 years). Most (78%) had visceral involvement and 63% had received earlier (neo)adjuvant chemotherapy. The objective response rate (RECIST) in 49 evaluable patients was 51% (95% confidence interval (CI), 36–66), including complete response in 4%. The clinical benefit rate (response or stable disease for ⩾6 months) was 63% (95% CI, 48–77). The median duration of response was 7.2 months (95% CI, 6.4–10.2). After a median follow-up of 41 months, median progression-free survival was 8.4 months (95% CI, 5.8–9.7) and median overall survival was 29.2 months (95% CI, 18.2–40.1). Treatment-related adverse events were manageable, the main grade 3–4 toxicity was neutropaenia (49%); two patients experienced febrile neutropaenia and three patients had a neutropaenic infection (including one septic death). A particularly low rate of alopaecia was observed.Conclusion:
These results show that the all-oral combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for MBC. 相似文献5.
García-Alfonso P Muñoz-Martin AJ Alvarez-Suarez S Jerez-Gilarranz Y Riesco-Martinez M Khosravi P Martin M 《British journal of cancer》2010,103(10):1524-1528
Background:
Combination of capecitabine and irinotecan (XELIRI regimen) is an active and well tolerated treatment for metastatic colorectal cancer (mCRC). The aim of this study was to evaluate the efficacy and safety of this regimen in combination with bevacizumab (BV), as first-line treatment for mCRC.Patients and methods:
A total of 46 consecutive patients received a combination of BV (5 mg kg−1, day 1), irinotecan (175 mg m−2, day 1) and capecitabine (1000 mg m−2 twice daily on day 2–8), every 2 weeks. Patients were treated until disease progression or unacceptable toxicity. The primary objective was to determine the progression-free survival (PFS) and safety profile.Results:
The overall response rate (ORR) was 67.4%, with a disease control rate (ORR+stable disease) of 93.5%. Median PFS and overall survival (OS) were 12.3 months (95% confidence interval (CI): 6.5–18.1 months) and 23.7 months (95% CI: 16.7–30.6 months), respectively. The most frequent grade 3/4 treatment-related adverse events were asthenia (7%), diarrhoea (7%), nausea (9%) and vomiting (7%).Conclusion:
Bevacizumab combined with biweekly XELIRI is a highly active first-line regimen for mCRC treatment, showing encouraging PFS, ORR and OS with a good tolerability. 相似文献6.
S Sutherland S Ashley D Miles S Chan A Wardley N Davidson R Bhatti M Shehata H Nouras T Camburn S R D Johnston 《British journal of cancer》2010,102(6):995-1002
Background:
The global lapatinib expanded access programme provided access to lapatinib combined with capecitabine for women with HER2-positive metastatic breast cancer (MBC) who previously received anthracycline, taxane and trastuzumab.Methods:
Progression-free survival (PFS) and safety data for 356 patients recruited from the United Kingdom are reported. Efficacy was assessed in 162 patients from the five lead centres, including objective tumour response rate (ORR), time to disease progression (TTP) and efficacy in those with central nervous system (CNS) metastases. Correlation of PFS and ORR with previous capecitabine treatment was also documented.Results:
Overall, PFS for the 356 UK patients was 21 weeks (95% CI: 17.6–24.7). In the 162 assessable patients, ORR was 21% (95% CI: 15–27%) and median TTP was 22 weeks (95% CI: 17–27). Efficacy was greater in capecitabine-naive patients (ORR 23 vs 16.3%, P=0.008). For 34 patients with CNS metastases, ORR was 21% (95% CI: 9–39%), with evidence of improvement in neurological symptoms, and median TTP was 22 weeks (95% CI: 15–28).Conclusions:
Lapatinib combined with capecitabine is an active treatment option for women with refractory HER2-positive MBC, including those with progressive CNS disease. 相似文献7.
Objective
The purpose of this study was to observe the efficacy and toxicities of capecitabine-based chemotherapy and capecitabine monotherapy as maintenance therapy in the treatment of metastatic breast cancer (MBC).Patients and methods
A total of 98 MBC patients were treated with capecitabine combined with vinorelbine (NX).Results
The median number of treatment was 6 cycles (1-7 cycles). There were two cases of complete remission (CR), 58 partial remission, 27 stable disease (SD), 11 progression disease. The overall response rate (ORR) (CR + PR) was 61.2%. The clinical benefit rate (CBR) was 75.5%. Fifty of effective patients received with capecitabine monotherapy as maintenance therapy. The ORR (CR + PR) was 4%. The CBR was 48%. The median progression-free survival (PFS) was 12 months. In maintenance therapy or not, the median post metastasis survival rate (MSR) was 63 and 28 months, respectively. In the combination therapy group, the major grade 3/4 toxicities included hand-foot syndrome (3.1%), skin pigmentation (2.0%), diarrhoea and abdominal distension (5.1%), stomatitis (1.0%), and leukopenia (20.4%).Conclusions
Capecitabine-based combination therapy and single-agent capecitabine maintenance therapy were well tolerated and effective to MBC. 相似文献8.
Joaquim Bellmunt Cristina Suarez Enrique Gallardo Jordi Rodon Francesc Pons Teresa Bonfill Marta Beltran Irene Moya Susana Galtes Joan Albanell Joan Carles 《The oncologist》2014,19(9):917-918
Background.
The combination of gemcitabine plus capecitabine and sunitinib (GCS) shows activity in metastatic renal cell carcinoma (mRCC). We tested the multitargeted “chemo-switch” regimen as first-line treatment in patients with mRCC.Methods.
We assessed the maximum tolerated dose and antitumor activity of GCS in treatment-naïve, advanced mRCC patients. Treatment consisted of intravenous gemcitabine on days 1 and 8, oral capecitabine twice daily on days 1–14, and oral sunitinib daily for six 21-day cycles, followed by sunitinib monotherapy at the investigator’s discretion. Dose level 0 (DL0) was gemcitabine 1,000 mg/m2 per day plus capecitabine 650 mg/m2 per 12 hours plus sunitinib 37.5 mg/day; DL1 was gemcitabine 1,000 mg/m2 per day plus capecitabine 850 mg/m2 per 12 hours plus sunitinib 37.5 mg/day.Results.
Sixteen patients were enrolled. At DL1, two of four patients had dose-limiting toxicity (DLT; grade 3 diarrhea and grade 4 thrombocytopenia). The dose was reduced to DL0 when only 1 of 12 patients experienced DLT (grade 3 diarrhea, grade 3 mucositis, and grade 3 thrombocytopenia). Dose reductions were frequent (58% of patients), and only seven patients were able to receive the three drugs for more than three cycles. One patient achieved a complete response, three had partial responses, and the best response for four was stable disease.Conclusion.
The safety profile of the combination does not seem manageable in this patient population. No further development of the combination is recommended. 相似文献9.
P Garcia-Alfonso A Mu?oz-Martin M Mendez-Ure?a R Quiben-Pereira E Gonzalez-Flores G Perez-Manga 《British journal of cancer》2009,101(7):1039-1043
Background:
Combination chemotherapy is standard treatment for metastatic colorectal cancer (MCRC). The aim of this study was to determine the efficacy and safety of capecitabine+irinotecan (2-weekly schedule), as first-line therapy of MCRC.Methods:
Patients received irinotecan 175 mg m−2 on day 1 and oral capecitabine 1000 mg m−2 twice daily on days 2–8 every 2 weeks. For patients aged ⩾65 years, the starting doses of irinotecan and capecitabine were reduced to 140 and 750 mg m−2, respectively.Results:
A total of 53 patients were enrolled: 29 (55%) were ⩾65 years old. In an intention-to-treat analysis, complete response was achieved in three patients for an overall response rate (ORR) of 32%. The disease control rate (ORR + stable disease) was 66% and the median duration of response was 7.3 months. Median time to progression and overall survival were 9.0 and 19.2 months, respectively. Grade 4 neutropenia was reported in one patient: no other grade 4 toxicities were recorded. Grade 3 diarrhoea occurred in 8 (15%) patients and grade 1–2 hand–foot syndrome in 7 (13%) patients.Conclusion:
Capecitabine and irinotecan, given every 2 weeks, as first-line treatment of MCRC is an active regimen with a manageable toxicity profile, even in older patients. 相似文献10.
Hope E. Uronis Johanna C. Bendell Ivy Altomare Gerard C. Blobe S. David Hsu Michael A. Morse Herbert Pang S. Yousuf Zafar Paul Conkling Justin Favaro Christy C. Arrowood Stephanie M. Cushman Kellen L. Meadows John C. Brady Andrew B. Nixon Herbert I. Hurwitz 《The oncologist》2013,18(3):271-272
Background.
Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. We evaluated the safety, tolerability, and efficacy of the combination capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas.Methods.
Thirty-seven patients with metastatic or unresectable gastric/gastroesophageal junction tumors were enrolled and treated with capecitabine 850 mg/m2 BID on days 1–14, and oxaliplatin 130 mg/m2 with bevacizumab 15 mg/kg on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Neuropilin-1 (NRP1) and -2 (NRP2) mRNA expression was evaluated in archived tumor.Results.
Thirty-five patients were evaluable for efficacy. Median PFS was 7.2 months; median OS was 10.8 months. RR was estimated at 51.4%. The regimen was tolerable with expected drug class-related toxicities. NRP2 mRNA levels significantly correlated with PFS (p = 0.042) and showed a trend toward significance with OS (p = 0.051). Nonsignificant trends for NRP1 were noted for higher expression levels and worse outcome.Conclusions.
Bevacizumab can be given safely with chemotherapy in patients with metastatic esophagogastric adenocarcinomas. The combination of capecitabine, oxaliplatin, plus bevacizumab has activity comparable to other bevacizumab-containing regimens in metastatic gastroesophageal cancer. 相似文献11.
Thuss-Patience PC Kretzschmar A Dogan Y Rothmann F Blau I Schwaner I Breithaupt K Bichev D Grothoff M Grieser C Reichardt P 《British journal of cancer》2011,105(4):505-512
Background:
No comparisons of different doses of docetaxel-capecitabine in patients with advanced gastric cancer have been performed.Methods:
Patients with previously untreated metastatic/locally advanced gastro-oesophageal or gastric adenocarcinoma were enrolled in a prospective multicentre phase II trial. Two sequential cohorts received docetaxel 75 mg m−2 (day 1) plus capecitabine 1000 mg m−2 twice daily (days 1–14) (cohort I) or docetaxel 60 mg m−2 (day 1) plus capecitabine 800 mg m−2 twice daily (days 1–14) (cohort II) every 3 weeks. The primary end point was confirmed overall response rate.Results:
In all, 91 patients were enrolled (cohort I, n=40; cohort II, n=51) and 87 were evaluable for efficacy (n=38, 49, respectively). Overall response rate was 50.0% in cohort I and 23.5% in cohort II (exploratory analysis, P=0.014). Median times to tumour progression and overall survival were 5.6 and 10.1 months in cohort I and 3.7 and 7.2 months in cohort II, respectively. Dose reductions for docetaxel and capecitabine were required in 50.0% and 57.5% of patients in cohort I and 11.8% and 15.7% in cohort II, respectively.Conclusion:
Starting treatment with full doses and reducing promptly seems to be the more promisingly effective strategy than starting cautiously with lower doses. Docetaxel/capecitabine 75/2000 mg m−2 is a manageable, convenient outpatient combination with promising efficacy against advanced gastric cancer. 相似文献12.
Yasuo Hamamoto Tatsuro Yamaguchi Tomohiro Nishina Kentaro Yamazaki Takashi Ura Takako Nakajima Ayumu Goto Ken Shimada Norisuke Nakayama Junichi Sakamoto Satoshi Morita Yasuhide Yamada 《The oncologist》2014,19(11):1131-1132
Background.
Capecitabine is used mainly with oxaliplatin to treat metastatic colorectal cancer (mCRC). Results from capecitabine plus irinotecan (XELIRI) with or without bevacizumab (BV) have been reported in Europe but not in Japan. Consequently, the safety and efficacy of XELIRI plus BV in Japanese patients with mCRC were assessed in a single-arm phase II study.Methods.
Eligible patients had had prior chemotherapy containing BV for mCRC and wild-type or heterozygous UGT1A1. Therapy in each 21-day treatment cycle consisted of capecitabine (800 mg/m2 twice daily on days 1–15), irinotecan (200 mg/m2 on day 1), and BV (7.5 mg/kg on day 1). The primary endpoint was dose-limiting toxicity in phase I and progression-free survival (PFS) in phase II.Results.
A total of 34 patients (6 in phase I, 28 in phase II) were enrolled from May 2010 to June 2011. Baseline characteristics included a median age of 60 years (range: 22–74 years) for 24 men and 10 women. No dose-limiting toxicities appeared in phase I. Median PFS was 240 days (95% confidence interval: 179–311 days). Overall response rate was 18.1%, and the disease-control rate was 90.9%. The incidence of adverse events frequently associated with irinotecan and capecitabine were neutropenia (any grade, 55.9%; grade 3 or 4, 11.8%), diarrhea (any grade, 50%; grade 3 or 4, 5.9%), and hand-foot syndrome (any grade, 61.8%; grade 3 or 4, 5.9%).Conclusion.
Our results suggest that XELIRI plus BV is well tolerated and effective as a second-line treatment for mCRC in Japanese patients. This regimen could be especially appropriate for patients resistant to oxaliplatin-based regimens. 相似文献13.
Tetsuya Taguchi Daigo Yamamoto Norikazu Masuda Koji Oba Takahiro Nakayama Takuya Nagata Masaya Nomura Katsuhide Yoshidome Hiroshi Yoshino Nobuki Matsunami Masaru Miyashita Yoshihiko Furuya Takanori Ishida Kazuyuki Wakita Junichi Sakamoto Shinzaburo Noguchi 《Cancer chemotherapy and pharmacology》2013,71(3):741-747
Purpose
The combination of capecitabine and paclitaxel (XP) has demonstrated synergistic antitumor activity in preclinical models. The purpose of this phase II study was to evaluate the efficacy and safety of a monthly XP regimen in patients with metastatic breast cancer (MBC).Methods
Eligible patients had received one or fewer prior chemotherapy regimens for MBC. Patients received oral capecitabine of low dose (828 mg/m2 twice daily, days 1–21) plus paclitaxel (80 mg/m2, i.v., over 60 min, days 1, 8 and 15) every 28 days until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Progression-free survival (PFS), overall survival (OS) and safety were secondary endpoints. An exploratory analysis of efficacy according to hormone receptor (HR) status was performed.Results
Forty-four patients were enrolled, and 43 patients were evaluable. ORR was 46.5 %. PFS and OS were 8.3 and 22.9 months, respectively. ORR was 45.5 % in patients with HR-positive tumors and 50 % in HR-negative cases. The most frequently observed grade 3/4 adverse events were neutropenia (27.9 %), leukopenia (11.6 %), hand-foot syndrome (HFS, 9.3 %) and fatigue (7.0 %). There were no discontinuations due to HFS.Conclusions
Monthly XP was an effective and well-tolerated regimen for the first- or second-line treatment for MBC. 相似文献14.
Daniel Frank Alcee Jumonville Noelle K LoConte William R Schelman Daniel Mulkerin Sam Lubner Katie Richter Natalie Winterle Mary Beth Wims Leah Dietrich J. Mitchell Winkler Michael Volk KyungMann Kim Kyle D. Holen 《Journal of gastrointestinal oncology.》2012,3(2):90-96
Background
Prognosis remains poor after progression on first-line chemotherapy for colorectal adenocarcinoma, and inactivation of the EGFR pathway with monoclonal antibodies is an effective treatment strategy in selected patients with metastatic disease. Lapatinib is an oral EGFR and HER-2 dual tyrosine kinase inhibitor that has not shown significant activity in metastatic colorectal cancer. However, lapatinib may act synergistically with capecitabine in anticancer effects.Methods
This was an open-label, non-randomized phase II study of lapatinib 1,250 mg orally daily and capecitabine 2,000 mg/m2 by mouth split into twice-daily dosing for 14 days of a 21 days cycle. Inclusion criteria included metastatic or locally advanced adenocarcinoma of the colon or rectum with progression by RECIST on or within six months of receiving a fluoridopyrimidine-, oxaliplatin- or irinotecan-containing regimen. Prior EGFR monoclonal antibody was permitted. K-ras testing was not routinely performed and was not a part of the study protocol.Results
Twenty nine patients (16 M; 13 F) were enrolled in this study. There were no complete or partial responses. 41.4% of patients achieved stable disease as a best response. Median overall survival was 6.8 months, with a 1-year survival rate of 22%, and median progression-free survival was 2.1 months. The combination produced few grade 3 and no grade 4 toxicities. No grade 3 toxicity occurred in more than 10% of patients.Conclusions
Although capecitabine and lapatinib is well tolerated, it is not an effective regimen in patients with refractory colorectal adenocarcinoma.Key Words: Colorectal cancer, capecitabine, lapatinib, EGFR, Her-2 相似文献15.
Baird R Biondo A Chhaya V McLachlan J Karpathakis A Rahman S Barbachano Y Cunningham D Chau I 《British journal of cancer》2011,104(1):43-50
Background:
Capecitabine plus oxaliplatin (CAPOX) is an established treatment option in colorectal cancer, but can be associated with severe toxicities.Methods:
Following reporting of severe diarrhoea and dehydration with capecitabine 2000 mg m–2 per day plus oxaliplatin every 3 weeks (CAPOX 2000) in 2006, we instituted a policy change to reduce capecitabine dose to 1700 mg m–2 per day (CAPOX 1700). We undertook a retrospective analysis comparing toxicities encountered before and after this dose change.Results:
Of the 400 patients treated, no significant differences were seen between the CAPOX 2000 and CAPOX 1700 in grades 3 and 4 diarrhoea (21% vs 19% P=0.80), stomatitis (0% vs 1% P=0.50) or grades 2–4 hand foot syndrome (16% vs 11% P=0.18). Grades 3 and 4 neutropenia (9.5% vs 3.5% P=0.03) and all grades hyperbilirubinaemia (60% vs 40% P<0.0001) were significantly reduced with CAPOX 1700. Rates of hospitalisation due to toxicities were not different between two groups (13% vs 11% P=0.53).Conclusions:
No clinically or statistically significant differences in gastrointestinal toxicities or hospitalisation rate were seen after reducing our routine capecitabine dose from CAPOX 2000 to CAPOX 1700. 相似文献16.
S W Gollins S Myint S Susnerwala B Haylock M Wise C Topham L Samuel R Swindell J Morris L Mason E Levine 《British journal of cancer》2009,101(6):924-934
Background:
The aim of this study was to investigate the safety of neoadjuvant chemoradiation using radiotherapy (RT) combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery.Methods:
Forty-six patients were recruited and treated on the basis that MRI scanning had shown poor-risk tumours with threatening (⩽1 mm) or involvement of the mesorectal fascia. Conformal RT was given using 3 or 4 fields at daily fractions of 1.8 Gy on 5 days per week to a total dose of 45 Gy. Concurrently oral capecitabine was given twice daily throughout radiotherapy continuously from days 1 to 35 and intravenous irinotecan was given once per week during weeks 1 to 4 of RT. Dose levels were gradually escalated as follows. Dose level 1: capecitabine 650 mg m−2 b.i.d. and irinotecan 50 mg m−2; Dose level 2: capecitabine 650 mg m−2 b.i.d. and irinotecan 60 mg m−2; Dose level 3: capecitabine 825 mg m−2 b.i.d. and irinotecan 60 mg m2; Dose level 4: capecitabine 825 mg m−2 b.i.d. and irinotecan 70 mg m−2.Results:
Diarrhoea (grade 3, no grade 4) was the main serious acute toxicity with lesser degrees of fatigue, neutropenia, anorexia and palmar-plantar erythrodysesthesia. The recommended dose for future study was dose level 2 at which 3 of 14 patients (21%) developed grade 3 diarrhoea. Postoperative complications included seven pelvic or wound infections and two anastomotic and two perineal wound dehiscences. There were no deaths in the first 30 days postoperatively. Of 41 resected specimens, 11 (27%) showed a pathological complete response (pCR) and five (12%) showed an involved circumferential resection margin (defined as ⩽1 mm). The 3-year disease-free survival (intent-to-treat) was 53.2%.Conclusion:
In patients with poor-risk MRI-defined locally advanced rectal cancer threatening or involving the mesorectal fascia, preoperative chemoradiation based on RT at 45 Gy in 25 daily fractions over 5 weeks with continuous daily oral capecitabine at 650 mg m−2 b.i.d. days 1–35 and weekly IV irinotecan at 60 mg m−2 weeks 1–4, provides acceptable acute toxicity and postoperative morbidity with encouraging response and curative resection rates. 相似文献17.
Medley L Morel AN Farrugia D Reed N Hayward N Davies JM Kirichek O Thakker RV Talbot DC 《British journal of cancer》2011,104(7):1067-1070
Background:
This study sought to determine the safety of single agent capecitabine, a pro-drug of 5FU, in patients with metastatic non-pancreatic neuroendocrine tumours (NETs).Methods:
Multicentre phase II, first-line study design. Oral capecitabine was administered on days 1–14 of 3-week cycles.Results:
Treatment was safe and well tolerated. Common toxicities were diarrhoea and fatigue.Conclusion:
The study provides evidence to support the use of capecitabine as a substitute for infusional 5FU in the management of NETs. 相似文献18.
Lindsay B. Kilburn Mehmet Kocak Franziska Schaedeli Stark Georgina Meneses-Lorente Carrie Brownstein Sazzad Hussain Murali Chintagumpala Patrick A. Thompson Sri Gururangan Anuradha Banerjee Arnold C. Paulino Larry Kun James M. Boyett Susan M. Blaney 《Neuro-oncology》2013,15(6):759-766
Background
We conducted a phase I study to estimate the maximum tolerated dose and describe the dose-limiting toxicities and pharmacokinetics of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy to children with newly diagnosed brainstem or high-grade gliomas.Methods
Children 3–21 y with newly diagnosed intrinsic brainstem or high-grade gliomas were eligible for enrollment. The starting dose was 500 mg/m2, given twice daily, with subsequent cohorts enrolled at 650 mg/m2 and 850 mg/m2 using a 3 + 3 phase I design. Children received capecitabine at the assigned dose daily for 9 wks starting from the first day of radiation therapy (RT). Following a 2-wk break, patients received 3 courses of capecitabine 1250 mg/m2 twice daily for 14 days followed by a 7-day rest. Pharmacokinetic sampling was performed in consenting patients. Six additional patients with intrinsic brainstem gliomas were enrolled at the maximum tolerated dose to further characterize the pharmacokinetic and toxicity profiles.Results
Twenty-four patients were enrolled. Twenty were fully assessable for toxicity. Dose-limiting toxicities were palmar plantar erythroderma (grades 2 and 3) and elevation of alanine aminotransferase (grades 2 and 3). Systemic exposure to capecitabine and metabolites was similar to or slightly lower than predicted based on adult data.Conclusions
Capecitabine with concurrent RT was generally well tolerated. The recommended phase II capecitabine dose when given with concurrent RT is 650 mg/m2, administered twice daily. A phase II study to evaluate the efficacy of this regimen in children with intrinsic brainstem gliomas is in progress (PBTC-030). 相似文献19.
R Zarate J Rodríguez E Bandres A Pati?o-Garcia M Ponz-Sarvise A Viudez N Ramirez N Bitarte A Chopitea J Gacía-Foncillas 《British journal of cancer》2010,102(6):987-994
Background:
A dose-finding study was performed to evaluate the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD) and the recommended dose (RD) of escalating the doses of capecitabine and fixed doses of irinotecan and oxaliplatin on a biweekly schedule for metastatic colorectal cancer patients (mCRC). A pharmacogenomic analysis was performed to investigate the association between SNPs and treatment outcome.Methods:
Eighty-seven chemotherapy-naïve mCRC patients were recruited through a two-step study design; 27 were included in the dose-finding study and 60 in the pharmacogenomic analysis. Oxaliplatin (85 mg m-2) and CPT-11 (150 mg m-2), both on day 1, and capecitabine doses ranging from 850 to 1500 mg m-2 bid on days 1–7 were explored. Peripheral blood samples were used to genotype 13 SNPs in 10 genes related to drug metabolism or efficacy. Univariate and multivariate Cox analysis was performed to examine associations between SNPs, ORR and PFS.Results:
The capecitabine RD was 1000 mg m−2 bid. Diarrhoea and neutropenia were the DLTs. After a median follow-up of 52.5 months, the median PFS and OS were 12 (95% CI; 10.6–13.4) and 27 months (95% CI; 17.2–36.8), respectively.The GSTP1-G genotype, the Köhne low-risk category and use of a consolidation approach strongly correlated with decreased risk of progression. Patients with all favourable variables showed a median PFS of 42 months vs 3.4 months in the group with all adverse factors. A superior clinical response was obtained in patients with one GSTP1-G allele as compared with GSTP1-AA carriers (P=0.004).Conclusion:
First-line therapy with oxaliplatin, irinotecan and capecitabine is efficient and well-tolerated. The GSTP1 polymorphism A>G status was significantly associated with ORR and PFS in mCRC treated with this triplet therapy. 相似文献20.
C-H Hsu T-S Yang C Hsu H C Toh R J Epstein L-T Hsiao P-J Chen Z-Z Lin T-Y Chao A-L Cheng 《British journal of cancer》2010,102(6):981-986