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1.
Radiation recall phenomenon secondary to capecitabine: possible role of thymidine phosphorylase 总被引:1,自引:0,他引:1
Background: The first reported case of radiation (XRT) recall related to capecitabine described dermatitis in a previously radiated field in a breast cancer patient (Ortman; JCO). We previously reported the first case of recall syndrome manifesting as diffuse gastritis and duodenitis related to capecitabine with prior XRT with 5-FU in a pancreatic cancer patient (Saif; JARCET). We report here another pancreatic cancer patient with a radiation recall receiving capecitabine following capecitabine-XRT. Patients and methods: From April 2004 to June 2005, 20 patients with locally advanced pancreatic adenocarcinoma were treated with capecitabine 1,600 mg/m2 daily with concomitant radiation (5040cGy) Monday–Friday (weekends off) for a total of 6 weeks, followed by capecitabine 2,000 mg/m2 daily for 14 days every 3 weeks. One male patient with tumor in the neck and body of pancreas and not infiltrating the duodenum dropped hemoglobin to 7.3 g/dl at the end of the ninth week, and melena on rectal examination. Specimen of primary pancreatic ductal adenocarcinoma was obtained via EUS-guided biopsy before starting XRT on day 1 and utilized for RNA extraction. TP mRNA level was determined by real-time quantitative PCR (RT-Q-PCR). Results: Upper endoscopy revealed gastritis consistent with radiation toxicity. Colonoscopy was negative. Transfusion of three units of packed red blood cells (PRBCs) was given. The dose of capecitabine was reduced by 25%. His anemia continued to progress, a CT scan revealed 39% decrease in the tumor size (PR). Analysis of tumor specimen prior to the start of capecitabine-XRT showed TP expression of 183.16 (high). In addition to TP, DPD was 7.40, and TNF-alpha 4,114.56. Conclusion: We believe this case to be the second case of radiation recall presenting as diffuse gastritis in a patient receiving capecitabine after previous treatment with XRT. Further studies, including the role of TP are warranted into the pathogenesis of this unique phenomenon. 相似文献
2.
Krishnamurthi SS Brell JM Hoppel CL Egorin MJ Weaver KC Li X Ingalls ST Zuhowski EG Schluchter MD Dowlati A Cooney MM Gibbons J Overmoyer BA Ivy SP Remick SC 《Cancer chemotherapy and pharmacology》2009,63(3):441-450
Purpose To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of the combination of weekly oxaliplatin × 4,
weekly irinotecan × 4 and capecitabine Monday through Friday for 4 weeks of every 6 week cycle in patients with solid tumors;
to determine the pharmacokinetic profile of these agents in this combination; to observe patients for clinical anti-tumor
response.
Methods Twenty-two patients with metastatic solid tumors received oxaliplatin 60 mg/m2 weekly × 4, irinotecan beginning at a dose of 40 mg/m2 weekly × 4, and capecitabine Monday through Friday for 4 weeks of every 6 week cycle, initially at 1,000 mg twice daily (bid).
Results The MTD was oxaliplatin 60 mg/m2 weekly × 4, irinotecan 50 mg/m2 weekly × 4 and capecitabine 450 mg bid Monday through Friday for 4 weeks of every 6 week cycle. One of six patients at this
dose level developed DLT of nausea, vomiting, and diarrhea. Among patients treated with a constant capecitabine dose of 450 mg
bid, there was a higher mean AUC of 5-FU in women than in men (mean ± SD: 892 ± 287 nM h vs. 537 ± 182 nM h; Mann–Whitney
two-tailed, P = 0.02). There was one complete response in a patient with gastric cancer.
Conclusion The novel schedule of weekly oxaliplatin, weekly irinotecan, and capecitabine Monday through Friday, all administered for
4 weeks of every 6 week cycle, evaluated in this phase I trial is well-tolerated and demonstrated activity in a patient with
gastric cancer.
Supported in part by NIH grants U01 CA62502, M01-RR-00080, K12 CA76917 (SSK), P30 CA43703, U01-CA099168-01 and P30CA47904.
Published in part in: Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No
14S (July 15 Supplement), 2004: 2111. 相似文献
3.
A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer 总被引:10,自引:0,他引:10
Ngan SY Michael M Mackay J McKendrick J Leong T Lim Joon D Zalcberg JR 《British journal of cancer》2004,91(6):1019-1024
The purpose of the study was to determine the maximum-tolerated dose (MTD) of oral capecitabine, combined with concurrent, standard preoperative pelvic radiotherapy, when given twice daily, from Monday to Friday throughout the course of radiotherapy, for locally advanced potentially resectable rectal cancer. Maximum-tolerated dose was defined as the total (given in two equally divided doses) oral dose of capecitabine that caused treatment-related grade 3 or 4 toxicity in one-third or more of the patients treated. Radiotherapy involved 50.4 Gy given in 28 fractions in 5 weeks and 3 days. Eligible patients had a newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within 12 cm of the anal verge suitable for curative resection. Surgery was performed 4-6 weeks from completion of preoperative chemoradiotherapy. In all, 28 patients were enrolled in the study at predefined dose levels: 850 mg m(-2) day(-1) (n=3), 1000 mg m(-2) day(-1) (n=6), 1250 mg m(-2) day(-1) (n=3), 1650 mg m(-2) day(-1) (n=3), 1800 mg m(-2) day(-1) (n=8) and 2000 mg m(-2) day(-1) (n=5). The mean age was 62.3 years (range: 33-80 years). Five patients were female and 23 male. The median distance of tumour from the anal verge was 6 cm (range: 1-11 cm). Endorectal ultrasound was performed in 93% of patients. A total of 26 patients (93%) had T3 disease and two patients had resectable T4 disease. Dose-limiting toxicity (DLT) developed in one patient at dose level 1000 mg m(-2) day(-1) (RTOG grade 3 cystitis). Two of the five patients at dose level 2000 mg m(-2) day(-1) had a total of three DLT (grade 3 perineal skin reaction, grade 3 diarrhoea and grade 3 dehydration). Dose escalation of capecitabine was ceased at 2000 mg m(-2) day(-1) after reaching MTD. None of the eight patients at dose level 1800 mg m(-2) day(-1) developed DLT. All except one patient underwent surgery. A total of 15 patients had the clinical T stage reduced by at least one stage in pathologic specimens. Five patients (19%) achieved a pathologic complete response. We conclude that the MTD of capecitabine was reached at a dose level of 2000 mg m(-2) day(-1), given as 1000 mg m(-2) twice daily, from Monday to Friday throughout the course of preoperative pelvic irradiation of 50.4 Gy. For patients with resectable rectal cancer receiving concurrent, full dose radiotherapy, the recommended dose of capecitabine for further study is 1800 mg m(-2) day(-1) when given in this schedule. 相似文献
4.
Yixing Jiang Heath B. Mackley Eric T. Kimchi Junjia Zhu Niraj Gusani Jussuf Kaifi Kevin F. Staveley-O’Carroll Chandra P. Belani 《Cancer chemotherapy and pharmacology》2014,74(1):205-210
Purpose
Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. The median survival of locally advanced nonoperable disease is approximately 9 months. 5-FU-based chemoradiotherapy has been the standard treatment. However, the survival benefit of this approach is modest. To improve the efficacy of 5-FU-based chemoradiation therapy, we evaluated the safety and feasibility of the combination of capecitabine and erlotinib with radiotherapy in this group of patients.Experimental design
A traditional “3 + 3” dose escalation design was adopted in the study. A total of four dose levels were designed. For safety purpose, a minus I dose level (?I) was also planned. The ?I level consisted of capecitabine 600 mg/m2 and erlotinib 50 mg daily, and the remaining four dose levels were as follows: level I: capecitabine 600 mg/m2 bid (twice daily); level II: 700 mg/m2 bid; level III: 825 mg/m2 bid; and level IV: 925 mg/m2 bid. Erlotinib was administered at 100 mg daily at all dose levels. Erlotinib and capceitabine were given continuously Monday through Friday concurrent with radiotherapy (50.4 Gy in 28 fractions).Results
A total of 18 patients were consented. Fifteen patients were enrolled and completed therapy. No dose-limiting toxicity was observed. The most frequent side effects were lymphopenia, nausea, vomiting, diarrhea, electrolyte imbalances, and skin rashes. The majority of the toxicities were grade 1 and 2. No objective response was observed. The median progression-free survival was 0.59 years (95 % CI 0.31–1.1), and the median overall survival was 1.1 years (95 % CI 0.62–1.59).Conclusions
The combination of capecitabine and erlotinib with radiotherapy in locally advanced pancreatic cancer is well tolerated and feasible at the dose level of capecitabine 925 mg/m2 bid and erlotinib 100 mg daily. 相似文献5.
Andrew J Sykes Nick J Slevin Robert H MacDougall Janet A D Ironside Kathleen L Mais 《Radiotherapy and oncology》2004,71(1):81-84
Capecitabine is preferentially converted to 5-fluorouracil within tumours, exploiting the higher levels of thymidine phosphorylase (TP) found in areas of poor perfusion and hypoxia. In addition radiation leads to up regulation of TP expression. To exploit these advantages of capecitabine as a synchronous chemoradiotherapy agent patients with advanced squamous cell carcinoma of the head and neck were recruited into a phase I non-randomised dose finding study. Capecitabine was given twice daily, 7 days a week at a dose starting at 350 mg/m(2) bid. Radiotherapy using a beam directed technique was prescribed to 55 Gy in 20 fractions over 4 weeks. A total of 24 patients were treated. Dose-limiting toxicity (grade IV mucositis) was reached at a capecitabine dose of 550 mg/m(2) bid. Radiotherapy was completed without delay in all cases. There was no systemic drug related toxicity. Capecitabine offers the prospect of an orally administered drug for use synchronously with radiotherapy, which in doses up to 500 mg/m(2) bid is well tolerated. 相似文献
6.
Fakih MG Rajput A Yang GY Pendyala L Toth K Smith JL Lawrence DD Rustum YM 《International journal of radiation oncology, biology, physics》2006,65(5):1462-1470
PURPOSE: We conducted a Phase I study to determine the maximum tolerated dose (MTD) of neoadjuvant capecitabine, oxaliplatin, and radiation therapy (RT) in Stage II to III rectal adenocarcinoma. METHODS AND MATERIALS: Capecitabine was given orally twice daily Monday through Friday concurrently with RT. Oxaliplatin was given i.v. once weekly x 5 (for 5 weeks) starting the first day of RT. RT was given daily except on weekends and holidays at 1.8 Gy per fraction x 28. Escalation for capecitabine or oxaliplatin was to occur in cohorts of three patients until the maximum tolerated dose (MTD) was defined. Endorectal tumor biopsy samples were obtained before and on Day 3 of treatment to explore the effects of treatment on thymidine phosphorylase, thymidylate synthase, dihydropyrimidine dehydrogenase, DNA repair, and apoptosis. RESULTS: Twelve patients were enrolled on this study. Two of 6 patients at dose level (DL) 1 (capecitabine 825 mg/m2 orally (p.o.) given twice daily (b.i.d.); oxaliplatin 50 mg/m2/week) had a dose-limiting diarrhea. One of 6 patients at DL (-)1 (capecitabine 725 mg/m2 p.o., b.i.d.; oxaliplatin 50 mg/m2/week) experienced-dose-limiting diarrhea. Three of 11 patients who underwent resection had a complete pathologic response. No remarkable variations in rectal tumor biologic endpoints were noted on Day 3 of treatment in comparison to baseline. However, a higher apotosis index was observed at baseline and on Day 3 in complete pathologic responders (no statistical analysis performed). CONCLUSIONS: Capecitabine 725 mg/m2 p.o., twice daily in combination with oxaliplatin 50 mg/m2/week and RT 50.4 Gy in 28 fractions is the recommended dose for future studies. 相似文献
7.
Bonnefoi H Biganzoli L Mauriac L Cufer T Schaefer P Atalay G Piccart M 《European journal of cancer (Oxford, England : 1990)》2003,39(9):1277-1283
In breast cancer, chemotherapy regimens that include infusional 5-fluorouracil (5-FU) lead to high response rates, but require central venous access and pumps. To avoid these inconveniences, we substituted infusional 5-FU with capecitabine. The main objective of this study was to determine the maximum tolerated dose (MTD) of capecitabine when given in combination with fixed doses of epirubicin and cyclophosphamide (100 and 600 mg/m(2) day 1 every (q) 3 weeks) as primary treatment for large operable or locally advanced/inflammatory breast cancer without distant metastasis. Capecitabine was escalated from 750 mg/m(2) twice a day (bid) to 1250 mg/m(2) bid from day 1 to day 14 in four dose levels. Dose escalation was permitted if 0/3 or 1/6 patients experienced dose-limiting toxicity (DLT). A total of 23 patients were included and 117 courses were administered. At dose level 4, 2 of 2 patients presented DLTs defining the MTD. A high rate of capecitabine treatment modification was required with capecitabine 1050 mg/m(2) bid (dose level 3). 19 patients achieved an objective response (83%). In conclusion, we believe that capecitabine 900 mg/m(2) bid (dose level 2) is the recommended dose in combination with epirubicin 100 mg/m(2) and cyclophosphamide 600 mg/m(2). The acceptable toxicity profile and encouraging activity of this regimen warrant further evaluation. 相似文献
8.
Aristu JJ Arbea L Rodriguez J Hernández-Lizoain JL Sola JJ Moreno M Azcona JD Díaz-González JA García-Foncillas JM Martínez-Monge R 《International journal of radiation oncology, biology, physics》2008,71(3):748-755
PURPOSE: To identify the maximal tolerated dose level of preoperative intensity-modulated radiotherapy combined with capecitabine and oxaliplatin and to evaluate the efficacy. PATIENTS AND METHODS: Patients with rectal T3-T4 and/or N0-N+ rectal cancer received capecitabine 825 mg/m(2) twice daily Monday through Friday and oxaliplatin 60 mg/m(2) intravenously on Days 1, 8, and 15, concurrently with intensity-modulated radiotherapy. The radiation dose was increased in 5.0-Gy steps in cohorts of 3 patients starting from 37.5 Gy in 15 fractions (dose level [DL] 1). DL2 and DL3 were designed to reach 42.5 Gy in 17 fractions and 47.5 Gy in 19 fractions, respectively. RESULTS: No dose-limiting toxicity was observed at DL1 or DL2. Of the 3 patients treated at DL3, 1 presented with Grade 3 diarrhea, which was considered a dose-limiting toxicity, and 3 additional patients were added. Of the 6 patients treated at DL3, no new dose-limiting toxicities were observed, and DL3 was identified as the recommended dose in this study. Eight additional patients were treated at 47.5 Gy. Grade 2 proctitis was the most frequent adverse event (40%); Grade 3 diarrhea occurred in 2 patients (10%). All patients underwent surgery, and 17 patients (85%) underwent R0 resection. Four patients (20%) presented with a histologic response of Grade 4, 11 (55%) with Grade 3+, 2 (15%) with Grade 3, and 2 patients (10%) with Grade 2. CONCLUSION: The maximal tolerated dose in this study was 47.5 Gy. The high rates of pathologic response of Grade 3+ and 4 must be confirmed through the accrual of new patients in the Phase II study. 相似文献
9.
Marwan G Fakih Patrick J Creaven Nithya Ramnath Donald Trump Milind Javle Sandra Strychor Trisha V W Repinski Beth A Zamboni James K Schwarz Renee A French William C Zamboni 《Clinical cancer research》2005,11(16):5942-5949
PURPOSE: Docetaxel, cisplatin, and capecitabine are three active chemotherapeutic agents with different mechanisms of action. This phase I study investigated the feasibility and pharmacokinetics of this combination given on a weekly schedule. EXPERIMENTAL DESIGN: Docetaxel and cisplatin were given i.v. over 30 minutes on days 1 and 8 and capecitabine was given orally bid on days 1 to 14 (every 21 days). Escalation occurred in cohorts of three patients until the maximum tolerated dose was defined. Pharmacokinetics studies of docetaxel and total and ultrafiltrate platinum after cisplatin administration were done on cycle 1 (with capecitabine) and cycle 2 (without capecitabine). RESULTS: Twenty-five patients were enrolled. Two of six patients at dose level 5 had a dose-limiting infection and diarrhea. One of six evaluable patients at dose level 4 (27 mg/m2 docetaxel, 27 mg/m2 cisplatin, 825 mg/m2 capecitabine) had a dose-limiting hypomagnesemia. Pharmacokinetics of docetaxel were similar on cycles 1 and 2. Area under the plasma concentrations versus time curves of total platinum was significantly greater in cycle 2 compared with cycle 1 (P = 0.001). There was no difference in the disposition of docetaxel on cycles 1 and 2. CONCLUSIONS: The recommended docetaxel, cisplatin, and capecitabine dose for phase II studies is 27/27/825 mg/m2. The alteration in total and ultrafiltrate platinum disposition on cycle 2 compared with cycle 1 may be inherent to sequential cisplatin administration; however, prior treatment with capecitabine cannot be ruled out as a factor. 相似文献
10.
Antitumor activity of erlotinib in combination with capecitabine in human tumor xenograft models 总被引:1,自引:0,他引:1
Purpose: To examine the antitumor activity and tolerability of a combination comprising erlotinib and capecitabine in human colorectal,
breast and epidermal cancer xenograft models. Further aims of the study were to examine the effects of single-agent erlotinib
therapy on tumor growth, and on thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) levels, (enzymes which
activate and deactivate capecitabine, respectively) in tumor tissue. Methods: BALB/c nu/nu mice bearing LoVo and HT-29 (colon cancer), A-431 (vulval cancer), and KPL-4 and MAXF401 (breast cancer) human
tumors were treated with erlotinib 100 mg/kg/day and/or capecitabine 359 or 90 mg/kg/day, by oral administration once daily
for 14 days. Results: The maximum tolerated dose (MTD) of erlotinib, formulated in carboxymethylcelluose/Tween 80, was identified as 125 mg/kg/day.
Erlotinib at a dose of 100 mg/kg/day achieved significant tumor-growth inhibition in the, LoVo, KPL-4, and A-431 models. Some
inhibition of MAXF401 tumor growth was observed, but was not significant. In the HT-29 model, erlotinib showed less marked
but statistically significant antitumor activity. On day 15, mean tumor-growth inhibition in HT-29, LoVo, KPL-4, MAXF401,
and A-431 models was 46, 74, 71, 20, and 85%, respectively. Evaluation of erlotinib/capecitabine combination therapy, at sub-optimal
doses, in the three erlotinib-sensitive tumor models LoVo, KPL-4 and A-431, demonstrated at least additive activity with the
combination compared with the single agents. In the A-431 and LoVo models, the combination of agents had greater antitumor
activity than the single agent capecitabine alone at the MTD. Erlotinib in combination with capecitabine was not associated
with significantly increased toxicity compared with single-agent therapy. Erlotinib 100 mg/kg/day induced significant upregulation
of TP and DPD in the LoVo model, a significant upregulation of TP in the HT-29, MAXF401 and A-431 models, but had no obvious
effect on TP and DPD levels in the KPL-4 model. In the A-431 model, selective upregulation of TP by erlotinib 100 mg/kg resulted
in an increased TP:DPD ratio. In the LoVo model, immunohistochemistry revealed marked upregulation of TP (but not DPD by erlotinib).
Conclusions: Erlotinib inhibits tumor growth in a range of human tumor xenograft models, including breast and colorectal cancer (CRC).
Erlotinib and capecitabine demonstrated at least additive activity in LoVo, KPL-4 and A-431 tumor models. The antitumor activity
of the combination was greater than that of capecitabine alone at the MTD. Erlotinib treatment did affect the TP in the CRC
tumor models as confirmed immunohistochemically. The findings of this study support clinical evaluation of erlotinib, both
as a single agent and in combination with capecitabine, for the treatment of CRC and breast cancer. 相似文献
11.
目的 观察并比较伊立替康(CPT-11)联合卡培他滨(CAP)与奥沙利铂(L-OHP)联合CAP治疗晚期胃癌的近期疗效和毒副反应.方法 将63例晚期胃癌患者随机分为两组,CPT-11+CAP组32例,应用CPT-11联合CAP方案治疗;L-OHP+CAP组31例,应用L-OHP联合CAP方案治疗.2个周期后评价疗效及毒副反应,有效病例4周后进行疗效确认.结果 CPT-11+CAP组PR 13例,有效率为40.6%,中位无进展生存期为6.3个月.L-OHP+CAP组PR 12例,有效率为38.7%,中位无进展生存期为6.1个月.两组有效率及中位无进展生存期比较,差异均无统计学意义(P>0.05).两组的主要毒副反应为胃肠道反应、周围神经毒性和骨髓抑制.CPT-11+CAP组Ⅲ、Ⅳ度腹泻的发生率(28.1%)高于L-OHP+CAP组(3.2%,P=0.018),Ⅲ、Ⅳ度周围神经毒性的发生率(3.1%)低于L-OHP+CAP组(25.8%,P=0.027).两组均无化疗相关性死亡.结论 CPT-11联合CAP方案与L-OHP联合CAP方案对晚期胃癌均有较好的疗效,毒副反应均可耐受.Abstract: Objective To observe and compare the response rate and toxicity of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer.Methods Sixty-three patients with advanced gastric cancer were randomly divided into two groups.The CPT-11 + CAP group consisted of 32 patients who received irinotecan plus capocitabine: CPT-11 100 mg/m2 was injected in 90 minutes on d 1,8 ;capecitabine 2000 mg/m2, bid, with the first dose in the evening of day 1 and last dose the morning of day 15, repoated for every 21 days.The L-OHP + CAP group consisted of 31 patients who received oxaliplatin plus capecitabine: oxaliplatin 100 mg/m2 on day 1, capocitabine 2000 mg/m2, bid,with the first dose in the evening of day 1 and last dose the morning of day 15, repeated for every 21 days.Two or more cycle chemotherapy was completed in each group.Results In the CPT-11 + CAP group, no patient achieved complete response and 13 patients achieved partial response.The overall response rate was 40.6% (13/32), and the median progression-free survival time was 6.3 months.In the L-OHP + CAP group, no patient achieved complete response and 12 patients achieved partial response.The overall response rate was 38.7% (12./31), and the median progression-free survival time was 6.1 months.There was no significant difference between them (P > 0.05 ).The most common toxicities were gastrointestinal reaction,peripheral neuropathy and myelosuppression in the two groups.Patients in CPT-11 + CAP group experienced more Ⅲ/Ⅳ diarrhea (28.1%/3.2%, P =0.018).On the contrary, the rate of Ⅲ/Ⅳ neurotoxicity in the group B was higher (25.8%/3.1%, P = 0.027).No chemotherapy-related death occurred.Conclusion The therapeutic effects of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer are good and comparable, and their toxicities are tolerable. 相似文献
12.
Ohno S Mitsuyama S Tamura K Nishimura R Tanaka M Hamada Y Kuroki S;Kyushu Breast Cancer Study Group 《Anticancer research》2007,27(2):1009-1013
BACKGROUND: Capecitabine is a highly effective and well-tolerated treatment for metastatic breast cancer (MBC) and extends survival when combined with docetaxel. Capecitabine and cyclophosphamide are orally administered and have preclinical synergy and non-overlapping toxicities. PATIENTS AND METHODS: Sixteen pretreated MBC patients received escalating doses of oral capecitabine 628 to 829 mg/m2 twice daily (bid) plus oral cyclophosphamide 33 to 50 mg/m2 bid, on days 1 to 14 every 21 days. RESULTS: Among the ten patients receiving capecitabine/cyclophosphamide 829/33 mg/m2 bid on days 1 to 14, two experienced dose-limiting toxicities (DLT, treatment delay > 1 week due to grade 2 leukopenia). Because neither patient developed further grade > 1 toxicity and none of the patients experienced grade 3/4 toxicities or further DLTs, this dose level is the recommended regimen, producing partial responses in two of five evaluable patients. CONCLUSION: The recommended all oral capecitabine/cyclophosphamide combination regimen is well tolerated and active in MBC, and is being evaluated in a phase II study in anthracycline-pretreated MBC. 相似文献
13.
目的:比较全量或半量索拉非尼(Sor)联合卡培他滨(CAP)治疗肝细胞肝癌的疗效和不良反应。方法:收集2012年2月至2016年6月肝细胞肝癌患者38例,随机分为A组(全量Sor联合CAP,n=19)和B组(半量Sor联合CAP,n=19)。A组:Sor 400 mg/次,B组:Sor 200 mg/次,每天2次口服,连续服用,直到疾病进展或不能耐受不良反应为止。A、B组均联用CAP 850 mg/m2每次,每天2次口服,连用14天,休息1周,每21天重复。结果:A组部分缓解(PR)3例,稳定(SD)11例,进展(PD)5例,总有效率(ORR)为15.8%,疾病控制率(DCR)为73.7%,中位肿瘤进展时间(mTTP)为(4.5±0.3)个月,中位总生存期(mOS)为7.2个月[95%可信区间(95%CI):7.1~7.3]。B组PR 2例,SD 11例,PD 6例,ORR为10.5%,DCR为68.4%,mTTP为(4.4±0.4)个月,mOS为7.3个月(95%CI:7.2~7.4)。 两组的ORR比较,P=1.000;DCR比较,P=0.721;TTP比较,P=0.549;OS比较,P=0.265,差异均无统计学意义(P>0.05)。不良反应:A组除手足综合征和高血压发生率明显高于B组外,其它不良反应发生率无统计学差异。结论:半量Sor联合CAP治疗晚期肝细胞肝癌疗效与全量Sor联合CAP无显著差异,半量Sor联合CAP组的手足综合征和高血压的发生率显著低于全量Sor联合CAP组。 相似文献
14.
三维适形放疗联合卡培他滨治疗局部晚期胰腺癌的临床研究 总被引:1,自引:0,他引:1
目的观察三维适形放疗(3DCRT)联合卡培他滨治疗局部晚期胰腺癌的疗效和毒性反应。方法 37例局部晚期胰腺癌患者随机分为3DCRT联合卡培他滨组(实验组)18例和单纯3DCRT组(对照组)l9例,实验组接受三维适形放疗,总量50.4~54.0 Gy,1.8~2.0 Gy/次,5次/周,同时口服卡培他滨850 mg/m2,2次/d,周一至周五与放疗同步;对照组只接受三维适形放疗。放疗结束后停止2~3周后,两组均开始用吉西他滨1000 mg/m2第1、8天,每3周为1个疗程,共4疗程。观察两组近期疗效、1年生存率、临床受益反应和毒性反应。结果实验组完全缓解率1/18(5.5%),部分缓解率7/18(38.9%),总有效率44.4%;对照组完全缓解率1/19(5.3%),部分缓解率6/19(31.5%),总有效率36.8%,两组间差异无统计学意义(P>0.05)。实验组和对照组1年生存率分别为61.1%和47.4%(P>0.05)。中位生存期实验组较对照组延长1月,分别为12月(CI:10.34~13.66)和11月(CI:8.16~13.84)。实验组疼痛评分降低优于对照组(P<0.05);体重增加和Karnofsky评分升高实验组与对照组无差异(P>0.05)。两组血液毒性、胃肠道反应等发生率无差异(P>0.05),但实验组手足综合征的发生率较对照组高(P<0.01)。结论三维适形放疗联合卡培他滨治疗局部晚期胰腺癌,与单纯三维适形放疗相比,能明显改善患者的生活质量,不良反应可耐受,近期疗效和1年生存率无显著差异。 相似文献
15.
Nishimura G Terada I Kobayashi T Ninomiya I Kitagawa H Fushida S Fujimura T Kayahara M Shimizu K Ohta T Miwa K 《Oncology reports》2002,9(3):479-482
Thymidine phosphorylase (TP) converts 5'-deoxy-5-fluorouridine (5'-DFUR, doxifluridine), an intermediate metabolite of capecitabine, to 5-fluorouracil (5-FU). While dihydropyrimidine dehydrogenase (DPD) catalyzes 5-FU to inactive molecules. We investigated TP and DPD levels in tumor tissue to assess their clinical significance as indicators for selecting colorectal cancer patients for 5'-DFUR adjuvant chemotherapy. A total of 88 colorectal cancer patients were classified into Dukes' B and C groups and treated for 2 years with oral 5'-DFUR (800 mg/body/day). During the follow-up period, 20 of the 88 patients developed a recurrence. All the patients were examined retrospectively for primary tumor TP and DPD levels and clinical response to 5'-DFUR. Results showed that: a) median levels of TP and DPD in the primary tumor, measured by enzyme-linked immunosorbent assay (ELISA), were, respectively, 43.6 and 32.3 U/mg protein. Primary tumor TP levels of the 20 patients who had a recurrence were lower than those of the 68 patients with no recurrence (p=0.07); b) although there were no significant differences in clinicopathologic features between high and low median TP level groups, disease-free survival was better in the high TP than in the low TP group (89% vs. 64%, at year 4); and c) of patients classified into 4 groups such as high TP/DPD, high TP but low DPD, low TP but high DPD, and low TP/DPD, patients with high TP but low DPD had the best disease-free survival, whereas the low TP but high DPD group had the worst survival. These results suggest that TP and DPD levels in primary colorectal tumors may be a useful indicator for selecting patients likely to respond to 5'-DFUR adjuvant chemotherapy and probably capecitabine, a prodrug of 5'-DFUR. 相似文献
16.
Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial. 总被引:4,自引:0,他引:4
Viviane Hess Marc Salzberg Markus Borner Rudolf Morant Arnaud D Roth Christian Ludwig Richard Herrmann 《Journal of clinical oncology》2003,21(1):66-68
PURPOSE: Preclinical studies indicate positive interactions between capecitabine, an oral fluorouracil precursor, and gemcitabine, the current standard treatment for advanced pancreatic carcinoma (APC). In this study, we investigated the addition of capecitabine to gemcitabine treatment for patients with APC. PATIENTS AND METHODS: This multicenter study included patients na?ve to chemotherapy who had histologically or cytologically confirmed, nonresectable or metastatic pancreatic carcinoma. Gemcitabine was given at a fixed dose of 1,000 mg/m(2) on days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally bid for 14 days followed by a 1-week rest. The maximum-tolerated dose (MTD) was defined as one dose level below the dose causing dose-limiting toxicity (DLT) in >or= one third of a cohort of six patients. We included an additional 15 patients at the MTD. RESULTS: Thirty-six patients were included. DLT occurred at a dose of 800 mg/m(2) bid of capecitabine and consisted of myelotoxicity and mucositis. Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, in this regimen, the recommended dose of capecitabine is 650 mg/m(2) bid. In 27 patients with measurable disease, we observed one complete and four partial remissions. In addition, significant drops (> 50% from baseline value) of the tumor marker CA 19-9 occurred in 14 of 24 assessable patients. CONCLUSION: The combination of capecitabine and gemcitabine is well tolerated, with apparent efficacy in patients with APC. Therefore, it is currently being compared with gemcitabine monotherapy in a phase III study. 相似文献
17.
J L Grem N Harold J Shapiro D Q Bi M G Quinn S Zentko B Keith J M Hamilton B P Monahan S Donavan F Grollman G Morrison C H Takimoto 《Journal of clinical oncology》2000,18(23):3952-3963
PURPOSE: Fluorouracil (5-FU) given as a weekly, high-dose 24-hour infusion is active and tolerable. We evaluated an oral regimen of eniluracil (which inactivates dihydropyrimidine dehydrogenase [DPD]), 5-FU, and leucovorin to simulate this schedule. PATIENTS AND METHODS: Patients received a single 24-hour infusion of 5-FU (2,300 mg/m(2) on day 2) with leucovorin (15 mg orally [PO] bid on days 1 through 3) to provide reference pharmacokinetic data. Two weeks later, patients began treatment with eniluracil (20 mg) and leucovorin (15 mg) (PO bid on days 1 through 3) and 5-FU (10 to 15 mg/m(2) PO bid on day 2). RESULTS: Dose-limiting toxicity (diarrhea, neutropenia, and fatigue) was seen with 5-FU 15 mg/m(2) PO bid on day 2 given weekly for either 6 of 8 weeks or 3 of 4 weeks, whereas five of seven patients tolerated 5-FU 10 mg/m(2) PO bid given weekly for 3 of 4 weeks. Eniluracil led to a 35-fold reduction in 5-FU clearance. Fluoro-beta-alanine, a 5-FU catabolite, was not detected in plasma during oral 5-FU-eniluracil therapy. DPD activity was markedly suppressed in all patients during eniluracil therapy; the inactivation persisted after the last eniluracil dose; percentages of baseline values were 1.8% on day 5, 4.5% on day 12, and 23.6% on day 19. CONCLUSION: The recommended oral dosage of 5-FU (10 mg/m(2) PO bid) given with eniluracil and leucovorin is approximately 115-fold lower than the reference dosage for 24-hour infusional 5-FU. This difference is greater than expected given the reduction in 5-FU clearance. DPD inactivation persisted for several weeks after completion of eniluracil therapy. 相似文献
18.
胰腺癌中胸苷磷酸化酶和二氢嘧啶脱氢酶含量及其比值的测定 总被引:3,自引:1,他引:2
目的测定胰腺癌肿瘤组织中胸苷磷酸化酶(TP)和二氢嘧啶脱氢酶(DPD)的含量并计算两者的比值,为希罗达在胰腺癌的临床应用提供理论基础。方法选取20例胰腺癌患者,应用ELISA法测定肿瘤组织中TP和DPD的含量,计算两者的比值,并与癌旁正常组织作比较。结果肿瘤组织中TP的含量平均为癌旁正常组织的74倍(5~283倍),两者含量的差异有显著性(P<0.01)。肿瘤组织中DPD的含量也明显升高(P<0.01)。肿瘤组织与癌旁正常组织的TP/DPD比值差异有显著性(P<0.01)。结论胰腺癌中TP/DPD比值较正常胰腺组织明显升高,提示希罗达能在胰腺癌中进行选择性活化,对于治疗胰腺癌应有较高的应用价值。 相似文献
19.
Phase I trial evaluating the concurrent combination of radiotherapy and capecitabine in rectal cancer. 总被引:13,自引:0,他引:13
Jürgen Dunst Thomas Reese Thomas Sutter Helmut Zühlke Axel Hinke Katrin K?lling-Schlebusch Stefan Frings 《Journal of clinical oncology》2002,20(19):3983-3991
PURPOSE: To establish the feasibility of concurrent radiotherapy and capecitabine and define the maximum-tolerated dose (MTD) in patients with rectal cancer. PATIENTS AND METHODS: Thirty-six patients with rectal cancer received treatment in the adjuvant, neoadjuvant, or palliative setting with a total irradiation dose of 50.4 Gy with 1.8 Gy/d in approximately 6 weeks. Capecitabine was administered at escalating doses from 250 to 1,250 mg/m(2) bid (including weekends) for the duration of radiotherapy. The MTD was defined when two or more patients in a cohort of three or six patients experienced dose-limiting toxicities. RESULTS: Dose-limiting grade 3 hand-foot syndrome was observed in two of six patients treated at a capecitabine dose of 1,000 mg/m(2) bid. Other toxicities were generally rare and/or mild, with only one case of non-dose-limiting grade 3 diarrhea and a single patient with grade 3 skin toxicity. Myelosuppression consisted mainly of leukocytopenia, with a maximum severity of grade 2. Thus, a dosage of 825 mg/m(2) bid is the recommended dose level for further evaluation. One pathologic complete remission of a T3N1 tumor and nine partial remissions were observed in 10 patients treated in the neoadjuvant setting. CONCLUSION: The recommended dose for phase II evaluation is capecitabine 825 mg/m(2) bid, administered without break during a conventional radiotherapy period of about 6 weeks. This combined-modality approach proved to be a feasible and well-tolerated treatment option with promising preliminary efficacy results in rectal cancer. 相似文献
20.
Nishina T Hyodo I Miyaike J Inaba T Suzuki S Shiratori Y 《European journal of cancer (Oxford, England : 1990)》2004,40(10):1566-1571
The aim of this work was to determine whether intratumour contents of thymidine phosphorylase (TP), which converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil, and dihydropyrimidine dehydrogenase (DPD), which degrades 5-fluorouracil to inactive molecules, could be useful in predicting the response of patients with metastatic gastric cancer to chemotherapy using 5'-DFUR. Endoscopic biopsy specimens for the measurement of TP and DPD were obtained from the primary lesions before the start of combination chemotherapy, in which 5'-DFUR, cisplatin and mitomycin C were administered. TP and DPD were measured by enzyme-linked immunosorbent assays after the objective responses to chemotherapy had been confirmed. Twenty five patients were enrolled in this study and data for 22 patients in whom responses were confirmed were analysed. The median levels (ranges) of TP and DPD were 80 (4.9-360) and 44 (15-82) U/mg protein, respectively. The median value (range) of TP to DPD ratios was 1.9 (0.25-5.1). Eight patients with a complete or partial response to chemotherapy had significantly higher TP to DPD ratios than did the remaining patients with stable or progressive disease (P = 0.014). When a cut-off level of TP to DPD ratio was defined as the median value, the high-ratio group (n = 11) showed a significantly higher response rate (64% vs. 9.1%, P = 0.024) than the low-ratio group (n = 11). Overall survival of the high-ratio group was significantly longer than that of the low-ratio group (the median survival time; 300 days vs. 183 days, P = 0.047). The efficacy of 5'-DFUR could be optimised by preselecting patients with high TP/ DPD ratios in their tumour tissues, and this would be applicable to the treatment with capecitabine. 相似文献