Myelopathy after radiation therapy and chemotherapy with capecitabine and gemcitabine

This article describes a woman with metastatic upper gastrointestinal cancer who developed thoracic myelopathy unexpectedly after standard dosage and fractionation radiotherapy. She also was receiving capecitabine and gemcitabine concomitantly. There are few reported cases of chemotherapy potentiation of spinal cord radiation toxicity. These agents are known radiosensitizers, making it likely that they contributed to this adverse outcome. As these agents are increasingly incorporated into clinical trials of combined therapy, caution will be necessary in both trial design and clinical management.     

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer

Background

Substantial antitumor activity has previously been demonstrated with the addition of nab-paclitaxel (Abraxane [Celgene, Summit, NJ]), an albumin-bound formulation of paclitaxel, to gemcitabine in patients with advanced pancreatic cancer. Given preclinical evidence of synergy when a fluoropyrimidine is added to gemcitabine plus a taxane in a sequence-specific schedule, we conducted a phase I study to evaluate the combination of nab-paclitaxel, gemcitabine, and capecitabine administered biweekly in patients with metastatic pancreatic adenocarcinoma.

Materials and methods

Patients with previously untreated metastatic pancreatic cancer and an ECOG performance status of 0?C1 were eligible to participate. Study design utilized a 3?+?3 dose-escalation schema, with expanded cohort at maximum-tolerated dose (MTD). Treatment was administered in 14-day cycles, with capecitabine given on days 1?C7 and both gemcitabine (at fixed-dose rate infusion) and nab-paclitaxel on day 4 of each cycle. Dose-limiting toxicity (DLT) definitions included grade 3?C4 hematologic toxicities and grade 2?C4 hand?Cfoot syndrome, neuropathy, or diarrhea.

Results

Fifteen patients were enrolled across two dose levels. Final MTD was established at nab-paclitaxel 100?mg/m², gemcitabine 750?mg/m², and capecitabine 750?mg/m² twice daily. Patients received a median of four treatment cycles (range 1?C16). The most frequent adverse events (any grade) for the entire study cohort included fatigue, rash/hand?Cfoot syndrome, nausea/vomiting, diarrhea, neuropathy, and elevated liver function tests. Ten patients (66.7?%) experienced at least one grade 3?C4 adverse event. Grade 3?C4 hematologic toxicities were uncommon. Two of 14 evaluable patients (14.3?%) exhibited a partial response, and 6 of 12 patients (50?%) with elevated CA19?C9 at baseline had a ??50?% biomarker decline.

Conclusion

While well tolerated overall, this regimen demonstrated only modest antitumor activity in patients with metastatic pancreatic cancer. Recognizing the limits of cross-study comparisons and small sample size, these results do not match those reported at MTD in the phase I/II trial of gemcitabine/nab-paclitaxel. The lower doses used in the current study suggest that dose intensity may be a critical aspect to optimize multidrug regimens.     

Expanded phase II trial of gemcitabine and capecitabine for advanced biliary cancer

BACKGROUND: A phase 2 trial of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer led to an objective response in approximately 30% of patients and a median survival of 14 months. In the current study, the authors report further efficacy data of a larger cohort of such patients treated with the GemCap regimen. METHODS: Patients aged >18 years and who had a diagnosis of locally advanced biliary cancer received first-line treatment with capecitabine at a dose of 650 mg/m(2) twice daily for 14 days and gemcitabine at a dose of 1,000 mg/m(2) on Day 1 and Day 8, every 3 weeks until disease progression. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. RESULTS: Between July 2001 and January 2005, 75 patients were enrolled in the study. At a median follow-up of 9.5 months, the overall response rate was 29% (95% confidence interval [95% CI], 19.4-41%), with a median duration of 9.7 months (range, 3-36 months). Three patients achieved complete responses, with a median duration of 17 months (range, 9-27 months). The median progression-free survival and overall survivals were 6.2 months (95% CI, 4.4-8.3 months) and 12.7 months (95% CI, 9.5-31 months), respectively. CONCLUSIONS: The GemCap regimen is active in patients with biliary cancer. Randomized trials are warranted to define the impact of such a regimen on patient survival and quality of life.     

Phase II trial of carboplatin, gemcitabine, and capecitabine in patients with carcinoma of unknown primary site

BACKGROUND: The purposes of this study were to evaluate efficacy and toxicity of the combination of carboplatin, gemcitabine, and capecitabine in patients with carcinoma of unknown primary site (CUP). METHODS: Patients with CUP received carboplatin AUC 5 mg/mL a minute intravenously Day 1, gemcitabine 1000 mg/m(2) intravenously Days 1 and 8, and capecitabine 1600 mg/m(2) orally in divided doses, Days 1-14 of a 21-day cycle for up to 8 cycles. The primary endpoint of the study was objective response rate by intent-to-treat analysis. RESULTS: Thirty-three patients were treated (median age, 58 years; men:women ratio, 19:14). Most patients had a baseline performance status of 1. The objective response rate was 39.4% (95% CI, 22.9%-57.9%) in all patients, 36.4% in 22 patients with well to moderately differentiated adenocarcinoma, and 40.0% in 20 patients with liver metastases. Median progression-free survival time was 6.2 months (95% CI, 5.4%-8.0%), and median survival time was 7.6 months (95% CI, 6.3-14.1). One and 2-year survival rates were 35.6% and 14.2%, respectively. The most frequent grade > or =3 adverse events were neutropenia (67%), thrombocytopenia (48%), and anemia (33%). CONCLUSIONS: The combination of carboplatin, gemcitabine, and capecitabine is active in CUP, especially in patients with liver metastases. This regimen may be a potential therapy for CUP patients with good performance status, particularly those with a suspected origin below the diaphragm.     

Immunobiological effects of gemcitabine and capecitabine combination chemotherapy in advanced pancreatic ductal adenocarcinoma

Background:

Preclinical studies suggest that chemotherapy may enhance the immune response against pancreatic cancer.

Methods:

The levels of granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) and the associated inflammatory marker C-reactive protein (CRP) were assessed in 38 patients receiving gemcitabine and capecitabine combination chemotherapy for advanced pancreatic cancer within the TeloVac trial. Apoptosis (M30) and total immune response (delayed-type hypersensitivity and/or T-cell response) were also assessed and levels of apoptosis induction correlated with immune response. The telomerase GV1001 vaccine was given either sequentially (n=18) or concomitantly (n=24) with the combination chemotherapy.

Results:

There were no differences between baseline and post-treatment levels of CRP (P=0.19), IL-6 (P=0.19) and GM-CSF (P=0.71). There was a positive correlation between post-chemotherapy CRP and IL-6 levels (r=0.45, P=0.005) and between CRP with carbohydrate antigen-19-9 (CA19-9) levels at baseline (r=0.45, P=0.015) and post treatment (r=0.40, P=0.015). The change in CRP and IL-6 levels was positively correlated (r=0.40, P=0.012). Hazard ratios (95% CI) for baseline CA19-9 (1.30 (1.07–1.59), P=0.009) and CRP (1.55 (1.00–2.39), P=0.049) levels were each independently predictive of survival. The M30 mean matched differences between pre- and post-chemotherapy showed evidence of apoptosis in both the sequential (P=0.058) and concurrent (P=0.0018) chemoimmunotherapy arms. Respectively, 5 of 10 and 9 of 20 patients had a positive immune response but there was no association with apoptosis.

Conclusions:

Combination gemcitabine and capecitabine chemotherapy did not affect circulating levels of GM-CSF, IL-6 and CRP. Chemotherapy-induced apoptosis was not associated with the immunogenicity induced by the GV1001 vaccine in advanced pancreatic cancer.     

Cetuximab,gemcitabine and capecitabine in patients with inoperable biliary tract cancer: A phase 2 study

PurposeBiliary tract cancer is rare and has dismal prognosis. Chemotherapy has its role in inoperable disease but the role of targeted agents like cetuximab remains to be defined. On the basis of high epidermal growth factor receptor expression of biliary tract cancers this study aims to investigate the efficacy of cetuximab, gemcitabine and capecitabine in an exploratory phase 2 trial.Patients and methodsInoperable biliary tract cancer patients were treated with the combination of gemcitabine (1000 mg/m² on day 1 and 8), capecitabine (1300 mg/m²/d on day 1–14) and weekly cetuximab (400 mg/m² loading and 250 mg/m² maintenance dose) in 21-d cycles until progression or the appearance of intolerable side-effects.ResultsOut of 34 patients (mean age 59.7 years) accrued in this study 16 had intrahepatic, eight extrahepatic cholangiocarcinoma and 10 gall bladder cancer. The best overall response rate was 17.6% (two complete responses and four partial responses) and the clinical benefit rate was 76.5%. After a median of 15.4 months follow-up the median progression free survival was 34.3 weeks and the median overall survival was 62.8 weeks. The performance status and chemotherapy efficacy were independent and significant markers of survival. Only moderate side-effects were registered in this study. KRAS mutation was evaluable in 24 tumours, all of these were of wild type.ConclusionThe efficacy of cetuximab, gemcitabine and capecitabine combination is encouraging and a well tolerated treatment of inoperable biliary tract cancers.     

吉西他滨联合卡培他滨治疗难治性乳腺癌的临床研究

目的:观察吉西他滨联合卡培他滨治疗难治性乳腺癌的疗效和不良反应.方法:37例难治性乳腺癌患者,应用吉西他滨联合卡培他滨,持续应用至疾病进展或出现不能耐受的不良反应.并按WHO标准评价疗效及不良反应,随访生存情况.结果:在37例可评价的患者中,CR 3例,PR 12例,SD 13例,PD 9例.RR为40.54%;DCR为75.68%.中位TTP为9个月(95%CI:6.115-11.885M);中位OS为15个月(95%CI:10.663-19.337M).主要不良反应为骨髓抑制,其次为胃肠道反应.结论:吉西他滨联合卡培他滨治疗难治性乳腺癌有较好的疗效,不良反应可以耐受.     

Randomised phase II trial of gemcitabine plus vinorelbine vs gemcitabine plus cisplatin vs gemcitabine plus capecitabine in patients with pretreated metastatic breast cancer

Background:

An increasing proportion of patients are exposed to anthracyclines and/or taxanes in the adjuvant or neoadjuvant setting. Re-exposure in the metastatic stage is limited by drug resistance, thus evaluation of non-cross-resistant regimens is mandatory.

Methods:

Anthracycline-pretreated patients were randomly assigned to three gemcitabine-based regimens. Chemotherapy consisted of gemcitabine 1.000 mg m⁻² plus vinorelbin 25 mg m⁻² on days 1+8 (GemVin), or plus cisplatin 30 mg m⁻² on days 1+8 (GemCis), or plus capecitabine 650 mg m⁻² b.i.d. orally days 1–14 (GemCap), q3w. The primary end point was response rate.

Results:

A total of 141 patients were recruited on the trial. The overall response rates were 39.0% (GemVin), 47.7% (GemCis) and 34.7% (GemCap). Median progression-free survival was estimated with 5.7, 6.9 and 8.3 months, respectively. Corresponding median survival times were 17.5 (GemVin), 13.0 (GemCis) and 19.4 months (GemCap). Neutropenia ⩾grade 3 occurred in 16.7% (Gem/Vin), 4.4% (GemCis) and 0% (Gem/Cap), whereas non-haematological toxicities were rarely severe except grade 3 hand–foot syndrome in 2.0% of the GemCap patients (per patient analysis).

Conclusions:

This randomised phase II trial has revealed comparable results for three gemcitabine-based regimens regarding treatment efficacy and toxicity. Gemcitabine-based chemotherapy appears to be a worthwhile treatment option for pretreated patients with metastatic breast cancer.     

吉西他滨联合卡培他滨治疗一线耐药乳腺癌的临床观察

为了观察吉西他滨(GEM)联合卡培他滨治疗蒽环类和(或)紫杉类耐药性晚期乳腺癌的疗效和毒副反应,2003-01-2006-03应用GEM联合卡培他滨治疗蒽环类和(或)紫杉类药物耐药的晚期乳腺癌38例,每例治疗2～6个周期,评价疗效并记录毒副反应。38例患者中,CR4例(10.5%),PR12例(31.6%),SD14例(36.8%),PD8例(21.1%),总有效率为42.1%(16/38),临床获益率为78.9%(30/38),中位疾病进展时间为8.5个月(2～59个月),1、2年生存率分别为60.5%和31.6%。主要毒副反应为骨髓抑制、胃肠道反应和手足综合征,Ⅲ～Ⅳ度白细胞减少发生率较低,手足综合征和消化道反应以Ⅰ、Ⅱ度为主。初步研究结果提示,GEM联合卡培他滨对蒽环类物和(或)紫杉类耐药的转移性乳腺癌有较好疗效,且毒副反应可以耐受。     

The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis

Purpose We developed a laboratory based regimen called GTX which induces synergistic apoptosis in human pancreatic cancer cells. This retrospective review summarizes our clinical experience with GTX in an initial group of 35 patients; 66% untreated and 34% failed prior therapies. Methods All patients treated with GTX for metastatic pancreatic cancer, prior to initiation of a prospective phase II trial of GTX were assessed and followed until death. GTX consisted of capecitabine (X), 750 mg/m² p.o. BID on days 1–14, gemcitabine (G) (750 mg/m²) over 75 min and docetaxel (T) (30 mg/m²) on days 4 and 11. Thus one cycle of GTX was 14 days with 7 days off for a 21 day cycle. Tumor assessments were repeated every 3 cycles. Results All 35 patients had metastatic pancreatic cancer (94% liver, 6% lung sites). Grade 3–4 hematological toxicities were: leukopenia and thrombocytopenia—both 14%, and anemia 9%, respectively. The overall response rate of all 35 patients treated with GTX (from 0.5 cycles onward) was 29% (CR/PR) by WHO criteria, and 31% had a minor response or stable disease (MR, SD). At the metastatic sites for the 35 patients, there were 9% complete (CR) and 31% partial (PR) responses (total 40%). For the 31 patients who had their primary tumor (4 patients had a prior Whipple resection), there were 13% CR and 19% PR for a response rate of 32% at the primary tumor site. Overall median progression free survival of responders was 6.3 months (95% C.I. 4.4–10.4 months) and median survival was 11.2 months (95% C.I. 8.1–15.1 months). Survival after initiation of GTX at 12, 18, 24 and 30 months was 43, 29, 20, and 11%, respectively. Conclusion Our retrospective review suggests that GTX has potential as a regimen for untreated and treated metastatic pancreatic cancer. An erratum to this article can be found at     

Phase I study of biweekly oxaliplatin,gemcitabine and capecitabine in patients with advanced upper gastrointestinal malignancies

BackgroundOxaliplatin, gemcitabine and capecitabine are all active agents against upper gastrointestinal and pancreaticobiliary cancers.Patients and methodsPatients with upper gastrointestinal malignancies treated with 0–2 prior chemotherapy regimens received oxaliplatin (85–100 mg/m²) as a 2-h i.v. infusion with gemcitabine (800–1000 mg/m²) at a constant rate i.v. infusion (CI) of 10 mg/m²/min on days 1 and 15 of a 28-day cycle. Capecitabine (600–800 mg/m²) was administered orally twice a day on days 1–7 and 15–21. A three per cohort dose escalation schema was used to determine the maximum tolerated dose (MTD) and the dose-limiting toxic effects (DLTs) of this combination regimen.ResultsThirty patients with advanced upper gastrointestinal malignancies were enrolled. The MTD was defined as oxaliplatin 100 mg/m² i.v. over 2 h plus gemcitabine 800 mg/m² i.v. at a CI of 10 mg/m²/min on days 1 and 15 with capecitabine 800 mg/m² p.o. b.i.d. days 1–7 and 15–21 of a 29-day cycle. DLTs include grade 3 fatigue and grade 3 dyspnea. One complete and two partial responses were observed.ConclusionsThis biweekly schedule of oxaliplatin, gemcitabine and capecitabine is tolerable and warrants further investigation in biliary and pancreatic malignancies.     

Two cases of advanced pancreas cancer treated with GTX: combined use of gemcitabine, docetaxel and capecitabine

Two cases of advanced pancreas cancer were treated with GTX. One cycle was 3 weeks, capecitabine (1,000 mg/m(2)/day) was administered from day 1 to 14, and GEM 750 mg/m(2) and DOC 30 mg/m(2) were drip-infused on day 4 and 11. A 62-year-old man with pancreas head cancer and 2 liver metastases was treated with GEM 1,000 mg/m(2)/week at weeks 1, 2, and 3, and drug-free week 4 for 3 cycles, but was PD. After 3 cycles of GTX, the liver metastases decreased in size, and thereafter tumor markers became lowest after 7 cycles. The patient was shifted to another regimen after 14 cycles for 9 months of GTX. A 75-year-old man with pancreas head cancer and vascular invasion has been treated with GTX. As leukopenia was seen after the first cycle, the administration doses were reduced and GTX has been continued for a total 13 cycles. The tumor reduced in size and tumor markers decreased. GTX is suitable for outpatient chemotherapy with mild adverse effects.     

三维适形放疗同步卡培他滨联合吉西他滨治疗３２例局部晚期胰腺癌的临床观察

目的　探讨同步放化疗（ＣＣＲＴ）治疗局部晚期胰腺癌的疗效和毒性反应。方法　２００３年１月至２００６年２月共收治局部晚期胰腺癌患者３２例,采用三维适形放疗（３ＤＣＲＴ）,总量４５～５４Ｇｙ;同步化疗方案为：卡培他滨１５００ｍｇ／ｍ^２,分２次口服,第１～１４天;吉西他滨１０００ｍｇ／ｍ２,静脉滴注第１、８、１５天。２１天为１周期,与放疗同时开始,ＣＣＲＴ结束后１个月巩固化疗２～４周期。结果　所有患者均完成ＣＣＲＴ治疗,其中２１例完成４个周期巩固化疗,７例３个周期,４例２个周期。有效率为５６.２％,中位生存期为１８.８个月,１、２年生存率分别为４６.８％和２２５％;疼痛缓解率６５.６％（２１／３２）,生活质量明显改善,无治疗相关性死亡。结论　三维适形放疗同步卡培他滨联合吉西他滨治疗局部晚期胰腺癌疗效显著,能提高局部控制率,延长生存期,缓解疼痛,提高生活质量,且毒副反应能够耐受。     

Dose-escalation study of fixed-dose rate gemcitabine combined with capecitabine in advanced solid malignancies

Purpose  To define dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of capecitabine with fixed-dose rate (FDR) gemcitabine. Methods  Eligible adults (advanced solid tumor; performance status ≤2) received capecitabine 500 mg/m² PO BID days 1–14 and FDR gemcitabine (400–1,000 mg/m² escalated by 200 mg/m² increments) at 10 mg/m²/min days 1 and 8 on a 21-day cycle. A traditional 3 + 3 cohort design was used to determine the MTD. Results  Thirty patients (median age 59 years) were enrolled. The predominant grade ≥3 toxicity was myelosuppression, particularly neutropenia. At dose level 4 (1,000 mg/m² gemcitabine), two out of five evaluable patients had a DLT (grade 4 neutropenia ≥7 days). At dose level 3 (800 mg/m² gemcitabine), one patient had a DLT (grade 3 neutropenia ≥7 days) among six evaluable patients. Therefore, the MTD and recommended phase II dose was designated as capecitabine 500 mg/m² PO BID days 1–14 with 800 mg/m² FDR gemcitabine days 1 and 8 infused at 10 mg/m² per min on a 21-day cycle. Partial responses occurred in pretreated patients with esophageal, renal cell and bladder carcinomas. Conclusions  This regimen was well tolerated and may deserve evaluation in advanced gastrointestinal and genitourinary carcinomas. The results of this research appeared as abstract ID 13509 at the 2008 American Association of Clinical Oncology meeting in Chicago, IL, USA.     

Safety and pharmacology of gemcitabine and capecitabine in patients with advanced pancreatico-biliary cancer and hepatic dysfunction

Purpose

We assessed the impact of hepatic dysfunction on the safety and pharmacology of gemcitabine/capecitabine in patients with advanced pancreatico-biliary cancer.

Methods

We included 12 patients receiving 3 weekly gemcitabine 1,000 mg/m² day 1, 8 and oral capecitabine 650 mg/m² b.i.d. over 2 weeks until disease progression or intolerable toxicity. Patients were included into one normal hepatic function cohort [total bilirubin (TB) ≤15 μmol/L] and 3 cohorts with increasing TB (16–39, 40–80, >80 μmol/L). Three patients with a creatinine clearance <60 ml/min were also included. Patients were sampled for gemcitabine, difluoro-deoxy uridine, intracellular gemcitabine triphosphates, capecitabine, 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine and 5-fluorouracil up to 4 h after initiation of chemotherapy on day 1, and up to 90 min on day 8. All compounds were analyzed using validated liquid chromatography–tandem mass spectrometry. Nonlinear mixed-effect modeling was used for population analysis.

Results

Hepatic dysfunction was caused by intrahepatic cholestasis in 4 out of 8 patients (50 %) and extrahepatic cholestasis in another 4 patients (50 %). Dose-limiting toxicity was increasing hyperbilirubinemia and severe neutropenia in 2 patients each. Hepatic dysfunction was not associated with dose-limiting toxicity or severe hematological or non-hematological toxicity. However, hepatic dysfunction was associated with low clearance of both gemcitabine (p = 10^?3) and capecitabine (p = 10^?5), and low intracellular gemcitabine triphosphate concentrations (p = 10^?3).

Conclusions

Gemcitabine/capecitabine can be given at the standard dose in patients with severe hyperbilirubinemia, though the present data suggest that gemcitabine’s activity may be limited due to poor intracellular activation. In patients with severe hyperbilirubinemia, initial monotherapy with capecitabine should be considered, followed by the addition of gemcitabine with improving hyperbilirubinemia.     

吉西他滨联合卡培他滨治疗紫杉类化疗失败的晚期乳腺癌的临床观察

目的探讨吉西他滨联合卡培他滨治疗紫杉类治疗失败的晚期乳腺癌的临床疗效及不良反应。方法对2008年3月至2010年2月住院治疗的69例紫衫类及葸环类治疗失败的晚期乳腺癌患者给予吉西他滨（1000mg／m2）和卡培他滨（1500mg／m2）治疗，3周为1个疗程，至少经过2个疗程的治疗。结果完全缓解3例（4．3％），部分缓解27例（39．1％），稳定22例（31．9％），进展17例（24．6％），总有效率为43．5％，临床获益率为75．4％，中位无进展生存时间为8．2个月，中位生存时间为13．4个月。骨转移患者总有效率为100％，明显高于多发转移、肺部转移和肝脏转移等患者，差异有统计学意义（P〈0．05）。绝经前患者临床获益率明显高于绝经后患者，两组比较差异有统计学意义（P〈0．05）。不良反应以手足综合征和血小板减少为主，均为可逆性，无治疗相关死亡发生。结论吉西他滨联合卡培他滨治疗紫杉类化疗失败的晚期乳腺癌临床效果显著，对于骨转移患者和绝经前患者的治疗效果更佳。     

Bevacizumab combined with gemcitabine and capecitabine for advanced pancreatic cancer: a phase II study

A total of 50 patients with advanced pancreatic cancer were enrolled in a phase II study of bevacizumab 15 mg kg⁻¹, capecitabine 1300 mg m⁻² daily for 2 weeks and gemcitabine 1000 mg m⁻² weekly 2 times; cycles were repeated every 21 days. Radiological response rate was 22%; progression-free survival and over survival were 5.8 and 9.8 months respectively. Grade 3 or 4 toxicities included neutropaenia (22%), thrombocytopaenia (14%), thromboembolic events (12%), hypertension (8%) and haemorrhage (6%).     

Phase II clinical trial of capecitabine and gemcitabine chemotherapy in patients with metastatic renal carcinoma

We report a single institution phase II study of gemcitabine 1200 mg m(-2) i.v. on days 1 and 8 and capecitabine 1300 mg m(-2) twice daily on days 1-14 of each 3-week cycle in patients with metastatic renal carcinoma. Patients had a WHO performance status of 0, 1 or 2. Of the 21 enrolled patients, 19 had received prior immunotherapy or chemoimmunotherapy. All had progressive disease at study entry. In all,19 patients had multiple sites of disease. The median duration of metastatic disease was 12.3 months (range 1.2-78.1 months). Three of the 19 evaluable patients achieved a partial response to treatment, with no complete responses, producing an objective overall response rate of 15.8% (95% CI, 3.4-39.6%). The median time to disease progression was 7.6 months, and median overall survival was 14.2 months. Treatment was reasonably well-tolerated, neutropenia being the most frequently observed grade 3 or 4 toxicity, occurring in 57% of patients. Other side effects were consistent with the established toxicity profile of the two drugs, including diarrhoea, palmar-plantar erythema, fatigue, nausea, vomiting and infection. This combination of gemcitabine and capecitabine has modest activity in immunotherapy-refractory metastatic renal carcinoma with manageable toxicity.     

吉西他滨联合卡培他滨治疗难治性乳腺癌的临床观察

目的观察吉西他滨联合卡培他滨（GX方案）治疗术后复发的乳腺癌患者的疗效和不良反应。方法50例患者分别接受GX方案化疗3～6个周期,按世界卫生组织（WHO）标准评价疗效及不良反应。结果50例患者均可评价,其中完全缓解（CR）4例（8．0％）,部分缓解（PR）22例（44．0％）,稳定（SD）18例（36．0％）,进展（PD）6例（12．0％）。中位肿瘤进展时间（mTTP）为8．3个月（95％CI：6．55—10．89）,中位总生存时间（mOS）为18．0个月（95％CI：14．34～21．98）。主要不良反应为骨髓抑制和皮疹。结论GX方案治疗晚期乳腺癌安全有效,不良反应较轻,值得临床推广应用。     

吉西他滨联合卡培他滨治疗耐药转移性乳腺癌56例临床分析

为了评估吉西他滨(GEM)和卡培他滨(CAP)3周联合化疗方案在蒽环类和(或)紫杉类耐药的转移性乳腺癌(MBC)患者中的有效性和毒性,对56例既往用过蒽环类和紫杉类的MBC患者给予GEM1000mg/m2,静脉滴入30min,d1、d8;CAP2000mg/m2,分2次口服,d1～d14,每3周为1个周期。所有患者均评估毒性,至少用过2个周期的患者评估疗效。结果:56例患者共完成196个周期化疗,中位化疗周期数为3.5个周期。完全缓解4例,部分缓解22例,稳定18例,进展12例,有效率为46.4%(26/56)。最常见的毒副反应为骨髓抑制和手足综合征。初步研究结果提示,GEM和CAP联合化疗方案在既往接受过蒽环类和紫杉类药物的MBC患者中是安全有效的,血液学和非血液学毒性都可耐受。