希罗达一线治疗晚期或复发性结直肠癌

目的　评价希罗达 一线治疗中国人晚期或复发性结直肠癌的疗效及安全性。方法6 0例晚期或复发性结直肠癌患者均给予希罗达 口服 ,每日 2次 ,餐后服用 ,12 5 0mg·(m2 )·-1次 -1,连续服用 14d后停药 7d。治疗周期为 2 1d ,至少治疗 2个周期。结果　本组部分缓解 (PR) 14例 ,病情稳定 (SD) 2 4例 ,疾病进展 (PD) 15例 ,总有效率 2 3.3% ,中位生存期为 14 .7个月 ,1年生存率为 6 3.9% ,2年生存率为 33.4 %。Ⅲ、Ⅳ级不良反应主要为腹泻 4例 ,贫血 2例 ,手足综合征 1例。Ⅰ、Ⅱ级不良反应为皮肤色素沉着 2 0例 ,手足综合征 18例 ,腹泻 10例。结论　希罗达 治疗中国人晚期或复发性结直肠癌疗效肯定 ,患者耐受性良好。     

希罗达(R)一线治疗晚期或复发性结直肠癌

目的评价希罗达(R)一线治疗中国人晚期或复发性结直肠癌的疗效及安全性.方法60例晚期或复发性结直肠癌患者均给予希罗达(R)口服,每日2次,餐后服用,1250mg@(m2)@-1次-1,连续服用14 d后停药7 d.治疗周期为21 d,至少治疗2个周期.结果本组部分缓解(PR)14例,病情稳定(SD)24例,疾病进展(PD)15例,总有效率23.3%,中位生存期为14.7个月,1年生存率为63.9%,2年生存率为33.4%.Ⅲ、Ⅳ级不良反应主要为腹泻4例,贫血2例,手足综合征1例.Ⅰ、Ⅱ级不良反应为皮肤色素沉着20例,手足综合征18例,腹泻10例.结论希罗达(R)治疗中国人晚期或复发性结直肠癌疗效肯定,患者耐受性良好.     

卡培他滨治疗蒽环类耐药的转移性乳腺癌

目的 研究卡倍他滨治疗既往蒽环类药物治疗失败的转移性乳腺癌患者的疗效和安全性。方法 17例具有可测量病灶的转移性乳腺癌患者接受卡培他滨（2510mg^2/天，口服14天，休息7天为一疗程）单药治疗2-6个疗程。结果 17例患者中CR1例，PR4例，SD4例和PD8例，有效率为29.3%。至疾病进展中位时间5个月（范围2-10^ 个月）。最常见的不良反应为手足综合征（64.7%)，皮肤色素沉着（58.8%)、白细胞减少（41.2%）和恶心呕吐消化道反应（17.6%），一般程度较轻，可耐受，Ⅲ度毒性反应为1例手足综合征，无IV度不良反应。应用Vitb6治疗能减轻手足综合征的症状。结论 卡培他滨治疗蒽环类药物治疗失败的转移性乳腺癌患者疗效好，不良反应少，且口服方便，对于晚期乳腺癌患者门诊治疗是一理想选择。     

奥沙利铂联合希罗达治疗晚期及复发性胃癌

0引言胃癌是我国最常见的恶性肿瘤之一,首选的治疗手段是手术切除病灶,但由于起病隐袭,症状不典型,胃癌的早期诊断较困难,故大多数患者就诊时已经属于晚期,丧失了手术切除机会,而晚期及复发性胃癌治疗主要是全身化疗。我科从2002年6月-2005年6月采用希罗达联合奥沙利铂治疗晚期及复发性胃癌,疗效显著,现报告如下：     

希罗达作为二线药物治疗晚期乳腺癌10例报告

目的 观察希罗达作为二线药物治疗晚期乳腺癌的疗效及安全性。方法 对10例具有可测量病灶的晚期乳腺癌患者采用希罗达（2510mg/m^2，每天1次，连服14天，21天为1个周期）单药治疗2－4个周期。所有患者既往均接受过1种以上化疗方案的化疗，其中7例患者接受过阿霉素和（或）紫杉醇治疗。结果 10例患者中3例接受了希罗达2个周期化疗，7例完成4个周期化疗。PR3例，MR1例，SD1例，PD5例。最常见的不良反应为恶心、皮肤色素沉着、厌食、疲劳和腹泻。Ⅲ度不良反应仅见于少数患者，其中腹泻1例、中性粒细胞减少1例、总胆红素升高4例。结论 希罗达作为二线药物治疗晚期乳腺癌的疗效较好且不良反应较轻，有望成为紫杉类或蒽环类药物治疗失败的乳腺癌患者的理想治疗药物。     

Second-line chemotherapy with Capecitabine (Xeloda) and Docetaxel (Taxotere) in previously treated, unresectable adenocarcinoma of pancreas: the final results of a phase II trial

Purpose

To investigate the efficacy and toxicity of the docetaxel and capecitabine combination in patients with previously treated, unresectable adenocarcinoma of the pancreas.

Patients and Methods

Patients with pancreatic adenocarcinoma, pre-treated with gemcitabine-based chemotherapy, were treated with capecitabine (800?mg/m² orally, twice a day for 14?days) and docetaxel (75?mg/m² i.v, on day1), every 3?weeks. The primary end-point was overall response rate (RR).

Results

Thirty-one patients were enrolled in the study; 93.6% of them had a performance status (PS) of 0?C1 and 96.8% had stage IV disease. Patients received a median of 4 cycles/patient, and the main reason for treatment discontinuation was disease progression. Partial response was observed in three (9.7%) patients, stable disease in seven (22.6%) (disease control rate: 32.3%, 95% CI: 15.80?C48.71%) and disease progression in 21 (67.6%). The median progression-free survival (PFS) was 2.4?months (95% CI: 1.6?C3.13) and the median overall survival (OS) was 6.3?months (95% CI: 3.38?C9.23); the estimated 1-year survival rate was 14.7%. Grade III/IV neutropenia occurred in 10 (32.2%) patients and febrile neutropenia in one patient. Other severe non-hematologic toxicities were mild and manageable. After 2 chemotherapy cycles, pain control occurred in 20% of patients and stabilization of body weight in 40%.

Conclusion

The combination of docetaxel/capecitabine may confer good disease control associated with improvement of quality of life as second-line chemotherapy in patients with metastatic pancreatic cancer.     

Capecitabine (Xeloda) in combination with oxaliplatin: a phase I, dose-escalation study in patients with advanced or metastatic solid tumors.

OBJECTIVES: This phase I, dose-escalation study was conducted to determine the recommended dose of intermittent oral capecitabine in combination with a fixed dose of i.v. oxaliplatin. Secondary objectives included evaluation of the safety profile and antitumor activity. PATIENTS AND METHODS: Twenty-three patients with advanced or metastatic solid tumors received a 21-day regimen of oral capecitabine (500, 825, 1000 or 1250 mg/m2 twice daily, days 1-14) in combination with oxaliplatin (130 mg/m2, 2-h i.v. infusion, day 1). Dose-limiting toxicities were determined during the first treatment cycle, and safety and efficacy were evaluated throughout treatment. RESULTS: The recommended dosing schedule is oral capecitabine 1000 mg/m2 twice daily (days 1-14) with i.v. oxaliplatin 130 mg/m2 (day 1) in a 21-day treatment cycle. The principal dose-limiting toxicity was diarrhea. The most frequent treatment-related adverse events occurring during the study were gastrointestinal (nausea/vomiting, diarrhea) and neurological (dysesthesia, paresthesia). The majority of treatment-related adverse events were mild to moderate in intensity, and no grade 4 adverse events occurred in the 15 patients treated at or below the recommended dose. The most common grade 3/4 laboratory abnormalities were lymphocytopenia (52% of patients), thrombocytopenia (22%; grade 3 only), neutropenia (17%) and hyperbilirubinemia (17%). Among patients treated at or below the recommended dose level (n = 15), only two patients experienced grade 3 neutropenia and no patients experienced grade 4 neutropenia. Partial tumor responses occurred in six patients (26%), including five of nine patients (55%) with colorectal cancer. All responding patients were pretreated with 5-fluorouracil and four responders had received prior irinotecan. CONCLUSIONS: Oral capecitabine with i.v. oxaliplatin is a feasible combination regimen that shows promising antitumor activity in patients with colorectal cancer. There is an ongoing, phase II study to further characterize the safety and efficacy of this combination as first-line therapy for metastatic colorectal cancer, using the recommended dose identified in this study.     

A Phase I Study of Irinotecan,Capecitabine (Xeloda), and Oxaliplatin in Patients With Advanced Colorectal Cancer

Background

The objective of the present phase I study was to define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of irinotecan, capecitabine, and oxaliplatin given in combination (IXO regimen) to patients with previously untreated, unresectable advanced or metastatic colorectal cancer (CRC).

Role of capecitabine (Xeloda) in breast cancer

One rationale for the development of new treatment strategies for advanced breast cancer is to provide targeted antineoplastic therapy, while at the same time improving the quality of life of patients. One such drug, capecitabine (Xeloda), is an oral fluoropyrimidine 5-fluorouracil carbamate. Capecitabine is converted to 5-fluorouracil primarily in cancer tissue and it has been demonstrated to combine ease of administration, a manageable toxicity profile and potent antineoplastic activity. Capecitabine is widely used in metastatic breast cancer and offers symptom palliation and in combination with docetaxel (Taxotere) improved survival compared with docetaxel alone. Its toxicity profile includes hand-foot syndrome and stomatitis and diarrhea, whereas its hematologic side effects are mild. Capecitabine has been evaluated as a single agent in women with advanced breast cancer where it offers an overall response rate of 20-30%. Capecitabine is synergistic with other chemotherapeutic agents, such as the taxanes, where it increases the response rate to over 40%. This review will place the available data on the use of capecitabine in metastatic breast cancer as a single agent or as part of a combination regime in context.     

Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma

Standard therapy for advanced or metastatic colorectal cancer consists of 5-fluorouracil plus leucovorin (5-FU/LV) administered intravenously (i.v.). Capecitabine (Xeloda), an oral fluoropyrimidine carbamate which is preferentially activated by thymidine phosphorylase in tumour cells, mimics continuous 5-FU and is a recently developed alternative to i.v. 5-FU/LV. The choice of oral rather than intravenous treatment may affect medical resource use because the two regimens do not require the same intensity of medical intervention for drug administration, and have different toxicity profiles. Here we examine medical resource use in the first-line treatment of colorectal cancer patients with capecitabine compared with those receiving the Mayo Clinic regimen of 5-FU/LV. In a prospective, randomised phase III clinical trial, 602 patients with advanced or metastatic colorectal cancer recruited from 59 centres worldwide were randomised to treatment with either capecitabine or the Mayo regimen of 5-FU/LV. In addition to clinical efficacy and safety endpoints, data were collected on hospital visits required for drug administration, hospital admissions, and drugs and unscheduled consultations with physicians required for the treatment of adverse events. Capecitabine treatment in comparison to 5-FU/LV in advanced colorectal carcinoma resulted in superior response rates (26.6% versus 17.9%, P=0.013) and improved safety including less stomatitis and myelosuppression. Capecitabine patients required substantially fewer hospital visits for drug administration than 5-FU/LV patients. Medical resource use analysis showed that patients treated with capecitabine spent fewer days in hospital for the management of treatment related adverse events than did patients treated with 5-FU/LV. In addition, capecitabine reduced the requirement for expensive drugs, in particular antimicrobials fluconazole and 5-HT3-antagonists to manage adverse events. As anticipated with an oral home-based therapy patients receiving capecitabine needed more frequent unscheduled home, day care, office and telephone consultations with physicians. In the light of clinical results from the phase III trial demonstrating increased efficacy in terms of response rate, equivalent time to progression (TTP) and survival (OS), and a superior safety profile, the results from this medical resource assessment indicate that capecitabine treatment of colorectal cancer patients results in a substantial resource use saving relative to the Mayo Clinic regimen of 5-FU/LV. This benefit is derived principally from the avoidance of hospital visits for i.v. drug administration, less expensive drug therapy for the treatment of toxic side-effects, and fewer treatment-related hospitalisations required during the course of therapy for adverse drug reactions in comparison to patients treated with 5-FU/LV.     

含卡培他滨方案治疗晚期消化道癌的临床观察

[目的]观察含卡培他滨方案治疗16例晚期消化道癌的疗效和毒副作用。[方法]卡培他滨剂量为每天2500mg/m^2，分两次口服，连服14天；部分联合草酸铂，剂量为130mg/m^2,d1，均3周为1个周期。[结果]14例有可观察病灶，均以CT检查结果作为测量病灶大小的依据，并以此评定治疗效果。总有效率（CR PR)为49.99%；完全缓解（CR）2例（14.28%），部分缓解（PR）5例（35.71%)；病情稳定（SD）6例（42.85%)；病情进展1例（7.14%)。临床获益患者（CR＋PR＋SD）92.86%。主要不良反应为手足综合征37.50%(6/16)，3例Ⅲ度（18.75%)，其余较轻；Ⅰ-Ⅱ度腹泻18.75%（3／16），1例十二指肠球部溃疡穿孔。Ⅰ-Ⅱ度贫血和白细胞下降18.75%(3/16)。[结论]含卡培他滨化疗方案治疗晚期消化道癌有较高的缓解率，较报道的单药治疗效果明显。副作用有手足综合征、轻度腹泻、轻度贫血和白细胞下降。对既往有消化道溃疡病史的患者使用时应特别慎重。     

Capecitabine: fixed daily dose and continuous (noncyclic) dosing schedule

Background: Oral fluoropyrimidines are presumed to emulate a parenteral continuous low-dose infusion delivery of the drug and the commonly used schedule is a 14 day on, 7 day off cycle at a total daily dose of 2500 mg/m² dose. There is a substantial incidence of diarrhea and hand/foot syndrome with this dose schedule. Objective: To retrospectively analyze a clinical experience with a fixed-unit daily dose of capecitabine employed continuously (open ended without cycling) as a single agent, in combination with other agents, or combined with radiation to determine the drug tolerability with regard to stomatitis, diarrhea, and hand/foot syndrome, compared with the “standard” dose schedule. Method: Fifty patients received 58 courses of continuous fixed daily dose capecitabine as a single agent (19 courses), combination with weekly irinotecan (15 courses); combined with 24-hour 5-fluorouracil (5-FU) infusion weekly (5 courses), combined with radiation (3 courses), or with other chemotherapy (16 courses). A fixed divided daily dose of 1500 or 2000 mg was administered for an open-ended period of time designed to deliver 10 weeks of continuous administration. Incidence and time to adverse event (toxicity) was determined for each course. Results: Capecitabine was administered continuously for 4 weeks to 8 months with a median of 3 months. Seven of 50 patients (14%) experienced grade 2 or 3 toxicity; hand/foot syndrome, 4 (8%); stomatitis plus diarrhea (grade 2), 1%; and diarrhea alone, 3 (6%). Four of the 7 patients developing toxicity received concomitant weekly 24-hour 5-FU and 3 patients received concomitant CPT 11 (1), doxil (1), or taxane (1). None of the patients on single-agent capecitabine (19) developed toxicity of any grade. The total daily dose of capecitabine was 830 to 1250 mg/m². The maximum dose intensity of the continuous fixed-dose schedule is 8750 mg/m²/week compared with 11,666 mg/m²/week for the standard dose and schedule (2500 mg/m²/day for 14 days every 21 days). Conclusion: Capecitabine administered as a continuous daily fixed dose has a low toxicity profile and can be administered in conjunction with other therapies relatively easily. This schedule provides for convenience and simplicity, and therapeutic effects are demonstrated even at low doses. The dose intensity of the noncycling continuous regimen is approximately 20% less than the standard cycling 2 weeks on every 21-day schedule.     

Mesothelioma from the patient's perspective

This study reports findings from qualitative semi-structured interviews with 15 patients who suffered from mesothelioma. The results are described under four headings that reflect the main themes that arose from the data: coping with symptoms (particularly breathlessness and pain), finding out about mesothelioma and its implications, the trauma of medical interventions, and psychosocial issues. The results illustrate the severe disease burden that is borne by people who have mesothelioma. It is hoped that a greater understanding of mesothelioma from a patient's perspective could inform the response of health care professionals.     

Recombinant antibodies: from the laboratory to the clinic

The development of recombinant antibodies has facilitated the exploitation of the Ab-Ag interaction specificity for targeted therapies. A fully human antibody, with custom integrated designs, can be obtained in one-third the time, compared to development of antibodies by hybridoma technology. Recombinant antibodies can be tailored for specific applications, "armed" with cytotoxic agents in a controllable fashion, and used for extracellular and intracellular targeting. Multitargeted and combination therapies are rapidly evolving for the treatment of cancer. Antibody therapeutics, costly to develop and produce, have proven beneficial in the clinic.     

A phase II trial of capecitabine (Xeloda) in recurrent ovarian cancer

Oral capecitabine is a highly active, well-tolerated and convenient treatment for breast and colorectal cancer. This trial assessed the efficacy and safety of single-agent capecitabine in patients with previously treated ovarian cancer. A total of 29 patients with platinum-pretreated relapsed ovarian cancer were enrolled in this prospective, open-label, single-centre, phase II study. Patients received oral capecitabine 1250 mg m(-2) twice daily on days 1-14 of a 21-day cycle. Tumour response was evaluated using serum CA125. Out of 29 enrolled patients, 28 were evaluable, and a response was observed in eight patients (29%, 95% confidence interval (CI), 13-49%). Median progression-free and overall survivals were 3.7 (95% CI, 2.8-4.6) and 8.0 (95% CI, 4.1-11.8) months, respectively. After 6 months of treatment, 28% (95% CI, 13-48%) of patients remained progression-free and 62% (95% CI, 42-79%) were still alive. The most common clinical adverse events were hand-foot syndrome (HFS), nausea and diarrhoea. Grade 3 HFS occurred in 14% of patients, grade 3 vomiting in 10%. Efficacy and safety of capecitabine compare favourably with other monotherapies in platinum-refractory epithelial ovarian cancer. The convenience and improved safety profile of capecitabine compared with intravenous. regimens make it an ideal agent for administration in the outpatient setting.     

The planned home care transfer by a local medical support hospital and the introduction to home intravenous hyper alimentation--the making of a home care patient's instruction plan document

It is important to offer continuous medical service without interrupting everyone's various job functions at the Tama Numbu-Chiiki Hospitals in order to secure the quality and safety of home medical care to patients and their families. From 1998 up to the present, home intravenous hyper alimentation (home IVH) has been introduced by individually exchanging information that was based on items such as clinical case, doctor and caregiver in charge of the day, and introductory information. Five years have passed since we started an introduction of home IVH, and it appears that the medical cooperation of home IVH between the Minami-tama medical region and its neighboring area has been established. Then, we arranged an examination of the past 2 years based on the 57 patients who elected to choose home IVH instruction. Consequently, we created "home IVH introduction plan document" in standardizing a flow from home IVH introduction to post-hospital intervention. Since November of 2003, the plan document has been utilized and carried out to 5 patients by the end of February in 2004. This home IVH introduction plan document was able to clarify the role of medical person in connection with the patient. Therefore, we could not only share the information, but also could transfer medical care smoothly from the hospital to the patient's home.     

Response of Neoplastic Meningitis from Solid Tumors to Oral Capecitabine

Neoplastic meningitis (NM) is a major challenge for the neuro-oncologist as it constitutes a relatively common clinical problem in systemic and central nervous system cancers, and is very difficult to treat. NM portends a significant worsening in prognosis. Chemotherapeutic treatment options are limited, and not particularly effective. We report two cases of NM from breast carcinoma and a third with esophageal carcinoma, which responded to treatment with capecitabine, an oral prodrug for 5-flurouracil. We believe capecitabine warrants further investigation in patients with NM. In some patients, its use may result in clinical and radiographic tumor responses, improved quality of life, and possibly increased survival.