Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015.

BACKGROUND: The study aimed to demonstrate the noninferiority of capecitabine to 5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival (PFS) after first-line treatment of metastatic colorectal cancer and the benefit of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with placebo (P). PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI: irinotecan (180 mg/m(2) i.v. on days 1, 15 and 22); FA (200 mg/m(2) i.v. on days 1, 2, 15, 16, 29 and 30); 5-FU (400 mg/m(2) i.v. bolus, then 22-h, 600 mg/m(2) infusion) or CAPIRI: irinotecan (250 mg/m(2) i.v. infusion on days 1 and 22); capecitabine p.o. (1000 mg/m(2) b.i.d. on days 1-15 and 22-36). Patients were additionally randomly assigned to receive either placebo or celecoxib (800 mg: 2 x 200 mg b.i.d.). RESULTS: The trial was closed following eight deaths unrelated to disease progression in the 85 enrolled (629 planned) patients. Response rates were 22% for CAPIRI + C, 48% for CAPIRI + P, 32% for FOLFIRI + C and 46% for FOLFIRI + P. Median PFS and overall survival (OS) times were shorter for CAPIRI versus FOLFIRI (PFS 5.9 versus 9.6 months and OS 14.8 versus 19.9 months) and celecoxib versus placebo (PFS 6.9 versus 7.8 months and OS 18.3 versus 19.9 months). CONCLUSION: Due to the small sample size following early termination, no definitive conclusions can be drawn in relation to the noninferiority of CAPIRI compared with FOLFIRI.     

Cost-effectiveness of second-line treatment with irinotecan or infusional 5-fluorouracil in metastatic colorectal cancer

Background:It has been shown that irinotecan is superior toinfusional 5-fluorouracil (5-FU) in patients with advanced colorectal cancerafter 5-FU failure. In a recent trial, median survival was 10.8 months forpatients treated with irinotecan, compared to 8.5 months in patients receivinginfusional 5-FU. Considering the statistically significant but clinicallyrelatively small advantage of irinotecan over 5-FU, cost effectiveness shouldalso be part of treatment decision. Purpose:To relate the costs of each management approach tooverall survival in patients with metastatic colorectal cancer. Patients and methods:The healthcare costs and medical benefits(treatment-added survival) of second-line chemotherapy in patients (infusional5-FU: 129, irinotecan: 127) were compared. Data on overall survival were drawnfrom a multicenter randomised trial that compared infusional 5-FU (continuousinfusion, AIO, or LV5-FU2 regimens) to irinotecan alone. Costs were derivedfrom the accounting system in two university hospitals in Paris, France. Results:The range in total healthcare costs was 14,135 to 12,192US$ patient between management approaches, with irinotecan chemotherapycosting most and 5-FU-continuous infusion least. If survival was included asa treatment benefit, the cost-effectiveness ratio of irinotecan over 5-FUranged from 9,344 to 10,137 US$ per year of added survival. Conclusions:The least expensive management for metastaticcolorectal was 5-FU infusion but the additional cost of irinotecan wasbalanced by the added months of survival, with a cost-effectiveness ratioclose to that of other cancer treatments.     

Two different first-line 5-fluorouracil regimens with or without oxaliplatin in patients with metastatic colorectal cancer

Background: Oxaliplatin, 5-fluorouracil (5-FU), and leucovorin(LV) are standard first-line treatments for patients with metastaticcolorectal cancer (mCRC). The aim of this multicentre, open-label,phase IIIb study was to assess the addition of oxaliplatin totwo different 5-FU regimens. Patients and methods: Patients with previously untreated mCRCwere randomised to arm A [two-weekly oxaliplatin 85 mg/m² +either continuous intravenous infusion (CIV) of 5-FU withoutLV or two-weekly bolus and CIV 5-FU + LV (LV5FU2)] or arm B(5-FU CIV or LV5FU2 alone). Irinotecan monotherapy was plannedon progression. Results: A total of 725 patients were enrolled. After a fixedfollow-up of 2 years for each patient, 2-year survival rateswere 27.3% and 24.8% in arms A and B, respectively (hazard ratio0.93; 95% confidence interval 0.78–1.10). The additionof oxaliplatin significantly improved response rates (54.1 versus29.8%; P < 0.0001) and median progression-free survival (7.9versus 5.9 months; P < 0.0001). The most common grade 3–4toxic effects were neutropenia (arm A, 33%; arm B, 5%), diarrhoea(arm A, 14%; arm B, 8%), and fatigue (arm A, 9%; arm B, 8%). Conclusions: Despite improved rates of tumour control, theseresults failed to demonstrate a survival benefit from the additionof oxaliplatin to infused 5-FU and lend further support to theuse of sequential monotherapy in some patients with mCRC. Key words: colorectal cancer, 5-fluorouracil, leucovorin, metastatic, oxaliplatin, phase III Received for publication May 12, 2008. Revision received July 16, 2008. Accepted for publication August 22, 2008.     

Oxaliplatin in combination with 5-fluorouracil/leucovorin or capecitabine in elderly patients with metastatic colorectal cancer

BACKGROUND: We evaluated the outcome of 140 patients aged > or = 70 years of age who received first-line treatment for metastatic colorectal cancer within the German phase III trial of FUFOX (5-fluorouracil/leucovorin/oxaliplatin) versus CAPOX (capecitabine/oxaliplatin). PATIENTS AND METHODS: One hundred forty (30%) elderly patients of 476 total patients were identified, and 138 patients received the CAPOX or FUFOX treatment. RESULTS: Overall, treatment was well tolerated, and grade 3/4 toxicities were similar in both groups, with more gastrointestinal side effects in the elderly group but less neurosensory side effects. The response rate (RR) was comparable between both cohorts (49% in elderly patients vs. 52% in patients aged < 70 years). Median progression-free survival (PFS) was 7.7 months for patients aged > or = 70 years and 7.5 months for patients aged < 70 years (hazard ratio [HR], 1.07; 95% CI, 0.86-1.34). With regard to the chemotherapy regimen, there was no inferiority between FUFOX and CAPOX in patients aged > or = 70 years (7.9 months vs. 7.6 months). The median overall survival (OS) between FUFOX and CAPOX was comparable in patients aged > or = 70 years (14.4 months vs. 14.2 months). However, when compared with patients aged < 70 years, the median OS was significantly shorter (18.8 months vs. 14.4 months; P = 0.013; HR, 1.37; 95% CI, 1.07-1.76). This was consistent with our multivariate analysis, which revealed that age > or = 70 years was a negative factor for OS. CONCLUSION: Oxaliplatin combined with 5-FU/leucovorin or capecitabine was generally well tolerated in elderly patients. Elderly patients had similar PFS and overall RRs compared with the population aged < 70 years, but the OS was shorter.     

Single-agent capecitabine in patients with metastatic colorectal cancer refractory to 5-fluorouracil/leucovorin chemotherapy

OBJECTIVE: The effectiveness of capecitabine, an oral fluoropyrimidine carbamate, is well documented in previously untreated metastatic colorectal cancer patients (overall response rate: 25%). However, its efficacy in patients with metastatic colorectal cancer refractory to 5-fluorouracil/leucovorin (5-FU/LV) has not been determined. This study was performed to evaluate the efficacy and to identify the side-effects of capecitabine in patients with metastatic colorectal cancer showing progression despite 5-FU/LV-based combination chemotherapy. METHODS: Fifty-one metastatic colorectal cancer patients who showed progressive disease in 5-FU/LV-containing regimens (median: two regimes) were treated with capecitabine 1,250 mg/m(2) twice daily (days 1-14 repeated every 3 weeks). RESULTS: Only one partial response was observed (response rate: 2%). Twenty-seven patients (53%) showed stable disease after two cycles. The median time to disease progression of either a partial response or stable disease was 3.4 months. Hand-foot syndrome was the main toxicity of capecitabine and occurred in 35% of cases (grade 3 or 4 in 6%). The median number of cycles administered was two and the relative dose intensity of capecitabine was 80%. CONCLUSION: The response rate to capecitabine was low in metastatic colorectal cancers that were refractory to 5-FU/LV-containing chemotherapy. However, disease stabilization was seen in a significant number of patients.     

A comparative study of oral tegafur and intravenous 5-fluorouracil in patients with metastatic colorectal cancer

A randomized study was conducted in patients who had measurable metastatic colorectal cancer to compare the relative efficacy and toxicities of oral tegafur (1 gm/m2/days 1-21) with those of 5-fluorouracil (5-Fu, 500 mg/m2/days 1-4, then 250 mg/m2 on days 6, 8, 10, 12). The treatment courses were repeated every 4 weeks. Patients not responding to 5-Fu treatment were switched to tegafur. Randomization was stratified for presence or absence of liver metastasis and performance status. Partial responses were observed with 5-Fu, 6/32 (19%), tegafur, 7/35 (20%), and in patients who had been switched to tegafur after failing on 5-Fu, 1/20 (5%) with patients evaluable for response. Neutropenia was more common with 5-Fu (32% vs. 1% of treatment courses). Nausea occurred in about half the treatment courses; vomiting occurred in only 22%. Mucositis and diarrhea were more common with 5-Fu and severe in patients with liver function impairment. Neurologic toxicities due to tegafur were mild and occurred in less than 10% of the treatment courses. Oral tegafur and I.V. 5-Fu were equally effective against colorectal cancer, but tegafur was associated with minimal myelosuppression, which makes it suitable for use in combination with myelosuppressive antitumor agents.     

Differences in efficacy and safety between capecitabine and infusional 5-fluorouracil when combined with irinotecan for the treatment of metastatic colorectal cancer

BackgroundCapecitabine is an oral fluoropyrimidine that is shown to have similar efficacy to 5-fluorouracil (5-FU) when used both alone and in combination with oxaliplatin in the treatment of colorectal cancer (CRC). Capecitabine and irinotecan combinations (XELIRI) have been developed for the treatment of this disease but randomized comparisons with standard infusional 5-FU and irinotecan (FOLFIRI) showed conflicting results.Patients and MethodsWe searched the literature for randomized controlled trials comparing XELIRI to FOLFIRI for the treatment of metastatic colorectal cancer. Odds ratios with 95% confidence intervals were used to analyze dichotomous variables. Hazard ratios for progression and death were combined with an inverse variance method based on logarithmic conversion. The fixed-effect model and Mantel-Haenszel method were used. Heterogeneity was investigated with the Q-test and I². Sensitivity analyses were performed.ResultsOnly 3 studies were identified, involving a total of 450 patients. XELIRI was associated with significantly shorter progression-free survival (PFS) and increased grade 3/4 gastrointestinal toxicities such as nausea, vomiting, and diarrhea. Severe neutropenia, however, was significantly more frequent with FOLFIRI. No differences in responses and febrile neutropenia events were observed.ConclusionOur analysis suggest that the 2 regimens are not equivalent. XELIRI remains an option for the first-line treatment of metastatic CRC but FOLFIRI should be preferred as it confers more benefits in terms of PFS and induces fewer GI toxicities.     

Pharmacogenetic approach for capecitabine or 5-fluorouracil selection to be combined with oxaliplatin as first-line chemotherapy in advanced colorectal cancer

We studied the role of TS (5’VNTR, 5’SNP and 3’UTR), XRCC1-399, XPD-751, ERCC1-118 and XRCC3-241 genetic polymorphisms in tailoring fluroropyrimidine/oxaliplatin treatment. For this purpose, 110 XELOX (capecitabine/oxaliplatin)- or FUOX (fluorouracil/oxaliplatin)-treated metastatic colorectal cancer patients were selected prospectively for genotyping. In the FUOX group, TS-3’UTR +6 bp/+6 bp (hazards ratio, HR = 2.62, p = 0.007) and ERCC1-118 C/T or C/C (HR = 1.96, p = 0.050) genotypes correlated with a shorter progression free survival (PFS). When analysed jointly, the higher the number of favourable genotypes (FG) the longer the PFS (6.8 m, 9.6 m and 25.8 m for 0, 1 or 2 FG; p = 0.005). Disease-control rate was 100% in patients with 2 FG (87% and 38.5% for 1 or 0 FG; p = 0.001). In the multivariate analysis, ERCC1-118 (HR = 2.12, p = 0.0037) and TS-3’UTR (HR = 2.68, p = 0.006) were strong independent prognostic factors. According to this, patients harbouring TS-3’UTR +6 bp/+6 bp and ERCC1-118 C/T or C/C genotypes may better receive capecitabine instead of 5FU in an oxaliplatin-based first-line treatment.     

First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin.

PURPOSE: To evaluate the safety profile of capecitabine using data from a large, well-characterized population of patients with metastatic colorectal cancer treated in two phase II studies. In these trials, capecitabine achieved significantly superior response rates, equivalent time to disease progression and equivalent survival compared with 5-fluorouracil (5-FU)/leucovorin. PATIENTS AND METHODS: Patients (n = 1207) were randomized to either oral capecitabine (1250 mg/m2 twice daily, on days 1-14 every 21 days) or intravenous (i.v.) bolus 5-FU/leucovorin (Mayo Clinic regimen). RESULTS: Capecitabine demonstrated a safety profile superior to that of 5-FU/leucovorin, with a significantly lower incidence of diarrhea, stomatitis, nausea, alopecia and grade 3 or 4 neutropenia leading to significantly fewer neutropenic fever/sepsis cases and fewer hospitalizations. All patients in the capecitabine group received a starting dose of 1250 mg/m2 twice daily and the majority (66%) did not require dose modification for adverse events. In the 5-FU/leucovorin group, 58% of patients did not require dose reduction for toxicities. The capecitabine dose-modification scheme reduced the recurrence of key toxicities without compromising efficacy. In both treatment arms, patients with moderate renal impairment at baseline (estimated creatinine clearance 30-50 ml/min) experienced a higher incidence of grade 3 or 4 toxicities. This increase was more pronounced with 5-FU/leucovorin. CONCLUSIONS: Capecitabine is at least as effective, better tolerated and more convenient than i.v. 5-FU/leucovorin as treatment for patients with metastatic colorectal cancer. Analysis of data from two large phase III trials demonstrates that efficacy is not compromised in patients requiring a dose reduction for adverse events. The phase III data and an additional pharmacokinetic study support a lower starting dose in patients with moderate renal impairment at baseline (calculated creatinine clearance 30-50 ml/min) and a contra-indication in patients with severely impaired creatinine clearance at baseline (<30 ml/min). For patients with normal or mildly impaired renal function at baseline, the standard starting dose is well tolerated. The incidence and severity of adverse events in patients with moderate renal impairment at baseline who were treated with 5-FU/leucovorin was more pronounced, indicating that capecitabine provides a better-tolerated alternative.     

A study of oral etoposide, infusional cisplatin, and infusional 5-fluorouracil for locally advanced or metastatic non-small-cell lung cancer. A Mid-Atlantic Oncology Program study.

A combination of oral etoposide, infusional cisplatin (24-hr) and infusional 5-fluorouracil (5-day) was used to treat 87 patients with non-small-cell lung cancer in a Phase II trial. Twenty-six patients were Stage IIIB, and 61 patients were Stage IV (new international classification). The regimen was well tolerated, with 49% grade 3 or 4 toxicities of all types. Response rates, partial and complete, were 40%, (95% confidence interval: 30%, 51%) for Stage IV patients and 20% (95% confidence interval: 10%, 32%), in Stage IIIB. An additional 68% of patients in Stage IIIB and 45% of patients in Stage IV achieved stable disease and had a median survival of 8.8 months, similar to that of patients in partial remission. Median survival was 5.6 months (95% confidence interval: 4.4 months, 10.8 months) for Stage IV patients and 11.0 months (95% confidence interval: 8.8 months, 12.4 months), for Stage IIIB. Of interest was the finding of a higher response rate in patients with a shorter duration of symptoms (less than 6 months versus greater than 6 months).     

卡培他滨治疗对氟尿嘧啶耐药的晚期转移性结直肠癌的效果观察

47例对5- 氟尿嘧啶(5- FU)耐药的晚期转移性结直肠癌患者接受卡培他滨(希罗达)治疗,根据WHO标准评价疗效及毒性反应,总有效率为17. 0%,平均反应持续时间为8 5个月, 原病情进展的患者有44. 7%经治疗后病情稳定, 病情稳定的平均时间4 8个月。有50%的病例在5个月内存在病情不再进展的可能性,自应用希罗达后的平均生存期为10 4个月,治疗前体质量持续下降的患者经3 个周期治疗有83. 0%(39/47)体质量稳定或增加。毒性反应中以恶心、腹泻、食欲减退、疲劳、手足综合征最为常见。初步研究结果提示,已经对5 -FU产生耐药性的晚期结直肠癌患者,经希罗达治疗,仍然有较高的有效率,而且毒性反应可以耐受,不影响继续治疗。     

Oxaliplatin in combination with infusional 5-fluorouracil and leucovorin every 2 weeks as first-line treatment in patients with advanced colorectal cancer: a phase II study

PURPOSE: To evaluate the efficacy and safety of oxaliplatin (L-OHP) in combination with leucovorin (LV)-modulated bolus plus infusional 5-fluorouracil (5-FU; de Gramont schedule) every 2 weeks in chemotherapy-naive patients with advanced colorectal cancer (CRC). PATIENTS AND METHODS: Thirty-two patients (median age: 69 years) with histologically confirmed and two-dimensionally measurable metastatic CRC were enrolled. The patients' performance status (WHO) was 0 in 14 (44%), 1 in 15 (47%), and 2 in 3 (9%) patients. Twenty (62.5%) patients had at least two metastatic sites. LV was administered at a dose of 200 mg/m2/day as a 2-hour intravenous infusion, followed by 5-FU as an intravenous bolus at the dose of 400 mg/m2 and then, as a 22-hour continuous infusion at the dose of 600 mg/m2/day for 2 consecutive days. L-OHP was administered on day 1 at the dose of 85 mg/m2 as a 2-hour infusion in parallel with LV but using different infusion lines. Treatment was administered every 2 weeks. RESULTS: In an intention-to-treat analysis, 2 (6.2%) complete and 9 (28%) partial responses (28%; odds ratio 34.2%; 95% confidence interval 17.92-50.83%) were achieved while 8 (25%) patients had stable disease and 13 (41%) progressive disease. The median duration of response was 5 months, but the median time to progression has not yet been reached. After a median follow-up period of 11 months, the median survival has not yet been attained, but the projected probability for 1-year survival was 72%. Grade 3/4 neutropenia occurred in 16 (50%) patients while 1 (3%) of them developed febrile neutropenia. There was no treatment-related death. Peripheral neuropathy grade 2 and > or =3 occurred in 5 (16%) and 7 (21%) patients, respectively. CONCLUSIONS: The bimonthly administration of L-OHP in association with LV-modulated bolus plus infusional 5-FU ('de Gramont' regimen) is a well-tolerated and effective front-line treatment for metastatic CRC.     

Cyclophosphamide, methotrexate and infusional 5-fluorouracil (infusional CMF) in metastatic breast cancer.

Bolus 5-fluorouracil (5-FU) is a phase-specific drug with a short plasma half-life that is used in combination with bolus cyclophosphamide and methotrexate in the treatment of breast cancer. The efficacy of 5-FU can be improved by continuous intravenous infusion using portable infusion pumps (infusional 5-FU). Infusional 5-FU, 200 mg m(-2) day(-1), in combination with standard doses of bolus cyclophosphamide and methotrexate, was evaluated in a phase I/II dose-finding study. The cyclophosphamide and methotrexate were administered in 28-day cycles as follows: cohort 1, cyclophosphamide 600 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 2, cyclophosphamide 400 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 3, cyclophosphamide 480 mg (m-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 4, cyclophosphamide 480 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), days 1 and 8. Median overall survival was 10 months (range 3-21 months). Objective tumour responses were seen in 9 of 25 patients (36%, 95% CI 18-58%), including 3 of 13 patients (23%) previously treated for metastatic disease. Cohorts 1 and 4 proved to be too toxic, with five of six patients in cohort 1 and three of four in cohort 4 developing grade III/IV neutropenia. The dose intensity of cyclophosphamide achieved was as follows: cohort 1, 82%; cohort 2, 86%; cohort 3, 97%; cohort 4, 90%. Infusional 5-FU can be administered safely and is effective in combination with cyclophosphamide 480 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1, in the treatment of metastatic breast cancer.     

Dichloromethotrexate, infusional cisplatin, and infusional 5-fluorouracil for locally advanced or metastatic non-small cell lung cancer. A MAOP study.

The combination of dichloromethotrexate, cisplatin, and infusional 5-fluorouracil was evaluated as treatment for non-small-cell lung cancer in a phase II trial using 43 evaluable patients. Grade III or IV toxicity included thrombocytopenia (21%), leukopenia (14%), nausea/vomiting (14%), mucositis (9%), infection (5%), and other (16%). There were six responders (14%), with a 95% confidence interval of [5%, 28%]. Two additional patients achieved a 50% reduction in cross-sectional tumor size that was not documented twice. Median survival time was 6.5 months. This combination is not considered sufficiently active for further evaluation in this disease.     

The efficacy and safety of capecitabine plus bevacizumab combination as first-line treatment in elderly metastatic colorectal cancer patients

Aim

The optimal treatment in older persons with metastatic colorectal cancer (mCRC) is complicated by a lack of general agreement. The aim of this study was to evaluate the activity of bevacizumab plus capecitabine combination in elderly mCRC patients who were not suitable for chemotherapy with irinotecan and oxaliplatin-containing regimens.

Materials and methods

Seventy years and older patients with metastatic colorectal carcinoma were included in this retrospective study. Bevacizumab was administered at a dose of 7.5 mg/kg on day 1 as an intravenous (IV) infusion over 30–90 min every 21 days, and capecitabine was prescribed at 1000 mg/m² twice daily on days 1–14 of the same 21-day schedule.

Results

Eighty-two consecutive patients (47 men, 35 women) were included in the study. The mean age was 75.5 (SD 3.9, range 70–87). Half of the patients were older than 75 years. There were 55 patients (67.1 %) with a good Eastern Cooperative Oncology Group (ECOG) performance status (PS: 0–1) and the remaining 27 patients (32.9 %) had a poor ECOG performance status (PS: 2). With a median follow-up period of 18.5 months, the median progression-free survival (PFS) was 10 months (95 % CI, 7.8–12.1) and the median OS was 25 months (95 % CI, 18.6–31.3). The main toxicities recorded were non-hematological. Thirty-one patients (37 %) experienced grade 3/4 adverse events, the most common being hand–foot syndrome (9.8 %). No fatal toxicity resulting from this regimen was recorded.

Conclusions

Considering the toxicity profile and survival outcomes, the combination regimen of capecitabine and bevacizumab is a potentially feasible treatment option in elderly mCRC patients.

     

Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer.

PURPOSE: To determine the safety and efficacy of capecitabine (Xeloda; Roche Laboratories, Nutley, NJ) in patients with metastatic or unresectable, locally advanced pancreatic cancer. PATIENTS AND METHODS: Forty-two patients were treated with oral capecitabine 1,250 mg/m(2) administered twice daily (2,500 mg/m(2)/d) as intermittent therapy in 3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment. Tumor lesions were assessed by computed tomography scan or physical examination at 6-week intervals (after every two cycles). Adverse events were monitored continuously during treatment and for 28 days after the last dose of study drug. RESULTS: Ten (24%) of 42 patients experienced a clinical benefit response (95% confidence interval [CI], 12.1% to 39.5%) as evidenced by improvement in pain intensity, analgesic consumption, and/or Karnofsky performance status. Three (7.3%) of the 41 patients with measurable disease had an objective response (partial). The median time to objective response was 85 days (range, 47 to 91 days) and duration of response was 208, 260, and 566 days for the three responding patients. One patient with nonmeasurable but assessable disease had improved residual disease with a positive clinical benefit response, for a total of four responses among the 42 assessable patients, for an overall response rate of 9.5% (90% CI, 3.3% to 20.5%). Capecitabine was generally well tolerated. CONCLUSION: Treatment with capecitabine resulted in clinically significant beneficial effects on tumor-related symptoms and yielded objective response activity in patients with metastatic or locally advanced pancreatic cancer. These results together with its generally tolerable safety profile and the added advantage of oral administration provide the basis for further evaluating capecitabine as a single agent or in combination with other treatment modalities in this patient population.