A phase II study of capecitabine plus gemcitabine in patients with locally advanced or metastatic pancreatic cancer

PURPOSE: This open-label, multicenter phase II study was conducted to investigate the efficacy and safety of capecitabine plus gemcitabine combination chemotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: We enrolled 63 patients who received capecitabine 830 mg/m(2) orally twice daily on days 1-21 plus gemcitabine 1000 mg/m(2) as a 30-min infusion on days 1, 8 and 15 every 4 weeks for up to six cycles. RESULTS: A total of 14 patients had partial responses giving an overall response rate of 22% (95% confidence interval [CI] 13-34%) in the intent-to-treat population. The median time to progression and overall survival were 3.9 months (95% CI 3.5-5.7) and 7.5 months (95% CI 5.0-10.0), respectively, and 1-year survival rate was 27.1% in the intent-to-treat population. Capecitabine plus gemcitabine was well tolerated. Grade 3 hematological adverse events were neutropenia (21%) and thrombocytopenia (2%); the only grade 4 hematological events were anemia (2%) and neutropenia (6%). Non-hematological adverse events were mainly gastrointestinal events and hand-foot syndrome, which affected 16% of patients. Grade 3/4 non-hematological events were infrequent. CONCLUSION: The combination of capecitabine plus gemcitabine appears to be active and well tolerated as first-line treatment in patients with advanced/metastatic pancreatic cancer.     

吉西他滨联合顺铂与单药吉西他滨治疗晚期胰腺癌的疗效比较

目的比较吉西他滨联合顺铂与单药吉西他滨治疗晚期胰腺癌的疗效。方法将53例局部晚期或转移性胰腺癌患者随机分两组,27例采用吉西他滨联合顺铂化疗(联合组),26例单纯应用吉西他滨化疗(单药组),对其疗效及毒副反应进行观察。结果可评估病例51例。联合组和单药组有效率分别为15.4%和12.0%(χ2=0.0031,P=0.9555),临床获益率(CR PR SD)分别为76.9%和44.0%(χ2=5.7955,P=0.0161);6个月生存率分别为73.1%和48.0%(χ2=3.3623,P=0.0667);CA199降低率分别为55.6%和47.6%(χ2=0.2444,P=0.6211);Ⅲ～Ⅳ度血液学毒性发生率分别为14.8%和11.5%(χ2=0.0029,P=0.9573)。结论吉西他滨联合顺铂与单药吉西他滨治疗晚期胰腺癌安全有效,前者在临床获益方面优于后者,在延长生存期方面也显示出一定的优势,但该差异未达到有显著性;在严重血液学毒性反应和降低CA199方面,二者差异无显著性。     

A pharmacological study of celecoxib and gemcitabine in patients with advanced pancreatic cancer

Purpose To evaluate whether celecoxib alters the conversion of gemcitabine into its active metabolite, difluorodeoxycytidine triphosphate (dFdCTP), in peripheral blood mononuclear cells (PBMCs).Methods Patients with advanced pancreatic cancer who had not received chemotherapy and had acceptable organ function were eligible for the study. The initial dose of gemcitabine was 750 mg/m² administered intravenously at a rate of 10 mg/m²/min on days 1, 8, and 15 every 4 weeks. Celecoxib was administered orally at 400 mg twice a day starting 2 days after the first dose of gemcitabine. Serial blood samples were taken during the first and second gemcitabine infusions and the cellular dFdCTP levels from PBMCs were analyzed.Results Five patients received gemcitabine at 750 mg/m² and six patients received it at 650 mg/m². Severe adverse events included neutropenia, thrombocytopenia, enteritis, and gastric perforation. Two patient died early during treatment. Cellular pharmacology studies showed that the conversion of gemcitabine into dFdCTP was not affected by celecoxib.Conclusion Despite the increased clinical toxicities encountered with the combination, celecoxib did not alter the conversion of gemcitabine into its active metabolites in PBMCs. Gemcitabine 650 mg/m² infusion over 65 min on days 1, 8, and 15 every 4 weeks in combination with celecoxib at 400 mg twice a day was the dose recommended for further study.     

Concurrent gemcitabine and radiotherapy with and without neoadjuvant gemcitabine for locally advanced unresectable or resected pancreatic cancer: a phase I-II study

PURPOSE: To determine the safety, efficacy, and tolerability of biweekly gemcitabine with concurrent radiotherapy (RT) for resected and locally advanced (LA) pancreatic cancer. METHODS AND MATERIALS: Eligible patients had either LA or resected pancreatic cancer. Between March 1999 and July 2001, 63 patients (31 with LA and 32 with resected disease) were treated. Of the 63 patients, 28 were enrolled in a Phase I study of increasing radiation doses (35 Gy [n = 7], 43.75 Gy [n = 11], and 52.5 Gy [n = 10] given within 4, 5, or 6 weeks, respectively, in 1.75-Gy fractions) concurrently with 40 mg/m(2) gemcitabine biweekly. Subsequently, 35 were enrolled in a Phase II study with the addition of induction gemcitabine 1000 mg/m(2) within 7 or 8 weeks to concurrent biweekly gemcitabine (40 mg/m(2)) and 52.5 Gy RT within 6 weeks. RESULTS: In the LA population, the best response observed was a complete response in 1, partial response in 3, stable disease in 10, and progressive disease in 17. In the phase II trial, gemcitabine plus RT was not delivered to 8 patients because of progression with induction gemcitabine alone (n = 5) or by patient request (n = 3). On intent-to-treat analysis, the median survival in the LA patients was 13.9 months and the 2-year survival rate was 16.1%. In the resected population, the median progression-free survival was 8.3 months, the median survival was 18.4 months, and the 2- and 5-year survival rate was 36% and 19.4%, respectively. The treatment was well tolerated; the median gemcitabine dose intensity was 96% of the planned dose in the neoadjuvant and concurrent portions of the Phase II study. No treatment-related deaths occurred. CONCLUSION: Biweekly gemcitabine (40 mg/m(2)) concurrently with RT (52.5 Gy in 30 fractions of 1.75 Gy) with or without induction gemcitabine is safe and tolerable and shows efficacy in patients with LA and resected pancreatic cancer.     

吉西他滨单药或与顺铂联合治疗胰腺癌的临床疗效评价

目的 评价吉西他滨单药以及与顺铂联合治疗局部晚期或转移性胰腺炎的疗效。临床受益反应,生存时间和毒性反应。方法 42例患者随机分为吉西他滨单药组（A组20例）和吉西他滨 顺铂联合组（B组22例）,A组;吉西他滨1000mg/m^2,每周1次,连用7周,休息1周;随后相同剂量每周1次,连用3周,休息1周,B组;吉西他滨1000mg/m^2,每周1次,连用3周,顺铂60mg/m^2,第15天给药,休息1周,每4周重复,边境用药3个周期。结果 42例患者中,可评价客观疗效者34例（A组16例,B组18例,可评价临床受益反应（CBR）者36例（A组16例,B组20例）,可进行毒性反应评估者40例（A组19例,B组21例）,A组：PR1例（6.3%)。MR4例（25.0%),SD7例（43.8%)。PD4例（25.0%)。B组;PR2例（11.0%)。MR3例（16.7%),SD8例（44.4%),PD5例（27.8%)。PR MR SD率A组为75.0%。B组为72.2%。CBR有效率A组为87.5%(14/16),B组为70.0%(14/20)。两组3个月生存率均为100%,6个月生存率分别为81.3%和61.6%。12个月生存率分别为31.3%和11.1%。B组Ⅲ、Ⅳ度血液学毒性反应发生率略高于A组,两组相比,差异无显著性。结论 吉西他滨单药以及与顺铂联合一线治疗局部晚期或转移性胰腺癌有一定的客观疗效。可明显改善患者的生活质量。延长了生存时间,患者耐受良好。     

Multi-institutional phase I study of low-dose ultra-fractionated radiotherapy as a chemosensitizer for gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer

PurposeGemcitabine (G) has been shown to sensitize pancreatic cancer to radiotherapy but requires lower doses of G and thus delays aggressive systemic treatment, potentially leading to distant failure. We initiated a phase I trial combining ultra-fractionated low-dose radiotherapy with full dose G and erlotinib in the treatment of patients with advanced pancreatic cancer.MethodsPatients with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status (PS) of 0–1 who had received 0–1 prior regimens (without G or E) and no prior radiotherapy were eligible. Patients were treated in 21 day cycles with G IV days 1 & 8, E once PO QD, and twice daily RT fractions separated by at least 4 h on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD).Results27 patients (median age 64 years and 15 male) were enrolled between 11/24/08 and 4/12/12. 1 patient withdrew consent prior to receiving any protocol therapy. 17 patients had a PS of 1. The majority of patients were stage IV. One DLT was noted out of 7 patients at dose level (DL) 1. Subsequently no DLTs were noted in 3 patients each enrolled at DL2-4 or 11 patients in the expansion cohort. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Best response in 24 evaluable patients: PR (8), stable (15), PD 1. Median survival for the entire group was 9.1 months.ConclusionThis phase I study combining low-dose ultra-fractionated RT as a sensitizer to full dose G plus E was well tolerated with encouraging efficacy. This represents a novel strategy worthy of further investigation in advanced pancreatic cancer patients.     

A triplet chemotherapy with cisplatin, docetaxel and gemcitabine in patients with advanced non-small-cell lung cancer: a phase I/II study

Purpose We conducted a phase I/II study of triplet chemotherapy consisting of cisplatin (CDDP), docetaxel (DCT) and gemcitabine (GEM) in patients with advanced non-small-cell lung cancer (NSCLC). Methods Fifty-three untreated patients with stage IIIB or IV NSCLC were enrolled. All drugs were given on days 1 and 8. The doses of CDDP and DCT were fixed at 40 mg/m² and 30 mg/m², respectively. In the phase I portion, a dose escalation study of GEM with starting dose of 400 mg/m² was conducted and primary objective in the phase II portion was response rate. Results The maximally tolerated dose (MTD) and recommended dose (RD) of GEM were determined as 800 mg/m² because grade 3 non-hematological toxicity (liver damage, diarrhea, and fatigue) developed in three of nine patients evaluated at that dose level. In pharmacokinetic analysis, C _max and AUC of dFdC and dFdU were increased along with the dose escalation of GEM. However, no relationship between pharmacokinetic parameters and toxicity or response was observed. Objective response rate was 34% and median survival time was 11.7 months. Though major toxicity was myelosuppression, there were no life-threatening toxicities. Conclusion These results indicate that this triplet chemotherapy is feasible and effective in patients with advanced NSCLC.     

A phase I study of gemcitabine plus palliative radiation therapy for advanced lung cancer

Purpose  To determine the maximum-tolerated dose (MTD) and antitumor activity of twice-weekly gemcitabine when combined with palliative-dose thoracic radiation therapy (RT) in patients with recurrent or progressive lung cancer. Methods  Patients were enrolled in a dose-escalating study of gemcitabine with a starting dose level of 40 mg/m² given as 30-minute infusions twice weekly concurrent with RT. The RT dose was 30 Gy in 10 fractions, 5 fractions per week. Results  A total of 18 patients were enrolled on three dose levels: 40, 50, and 65 mg/m². Four patients came off study early due to rapid progression of disease and therefore were not evaluated. The MTD of gemcitabine was found to be 50 mg/m². Dose-limiting toxicities were grade-4 esophagitis in one patient and grade-4 neutropenia in another patient. Overall response included 1 partial response (PR). Local response included six PR, four minor response (MR), three stable disease (SD), and one progressive disease (PD). Conclusion  The MTD of gemcitabine with concominant palliative thoracic radiation therapy is 50 mg/m² twice weekly. The DLTs observed were grade-4 esophagitis and grade-4 myelotoxicity at 65 mg/m².     

A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer

PURPOSE: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population. METHODS AND MATERIALS: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m(2) at 10 mg/m(2)/min) plus cisplatin 20 mg/m(2) on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m(2) orally twice daily on the day of radiation) as a radiosensitizer. RESULTS: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months. CONCLUSIONS: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation.     

A phase I trial of Capecitabine+Gemcitabine with radical radiation for locally advanced pancreatic cancer

Standard chemoradiotherapy with infusional 5FU for locally advanced pancreatic cancer (LAPC) has limited efficacy in this disease. The combination of Capecitabine (Cap) and Gemcitabine (Gem) are synergistic and are potent radiosensitisers. The aim of this phase I trial was thus to determine the highest administered dose of the Cap plus Gem combination with radical radiotherapy (RT) for LAPC. Patients had LAPC, adequate organ function, ECOG PS 0–1. During RT, Gem was escalated from 20–50 mg m⁻² day⁻¹ (twice per week), and Cap 800–2000 mg m⁻² day⁻¹ (b.i.d, days 1–5 of each week). Radiotherapy 50.4 Gy/28 fractions/5.5 weeks, using 3D-conformal techniques. Three patients were entered to each dose level (DL). Dose-limiting toxicity(s) (DLTs) were based on treatment-related toxicities. Twenty patients were accrued. Dose level (DL) 1: Cap/Gem; 800/20 mg m⁻² day⁻¹ (3 patients), DL2: 1000/20 (12 patients), DL3: 1300/30 (5 patients). Dose-limiting toxicities were observed in DL3; grade 3 dehydration (1 patient) and grade 3 diarrhoea and dehydration (1 patient). Dose level 2 was the recommend phase 2 dose. Disease control rate was 75%: PR=15%, SD=60%. Median overall survival was 11.2 months. The addition of Cap and Gem to radical RT was feasible and active and achieved at relatively low doses.     

Phase I and pharmacokinetic study of the novel redox-active agent, motexafin gadolinium, with concurrent radiation therapy in patients with locally advanced pancreatic or biliary cancers

Purpose: To determine the maximum tolerated dose and dose-limiting toxicity (DLT) of the novel anticancer agent, motexafin gadolinium (MGd), administered concurrently with radiation therapy (RT) in patients with locally advanced pancreatic or biliary tumors. The pharmacokinetics of MGd were also evaluated. Methods: Cohorts of three to six patients were treated with escalating doses of MGd, administered three times per week for a total of 16 doses concurrent with RT. The dose of RT was fixed at 5,040 cGy, and given in 28 fractions, from Monday to Friday of every week. Plasma MGd concentrations were measured by high performance liquid chromatography. Results: Eight patients were treated at dose level 1 (2.9 mg/kg), with one DLT (grade 3 fever). Three patients were treated at dose level 2 (3.6 mg/kg), and two DLTs were noted. One DLT was grade 3 nausea and vomiting (N/V), and the other was grade 3 skin toxicity. The most common toxicity was N/V. There were no objective responses. The median survival was 6 months. The MGd plasma concentration versus time profile in each patient was best fit by a two-compartment, open, linear model. There was minimal accumulation of MGd in plasma with the three-times/week dosing schedule. Simulation of the time course of MGd in the peripheral compartment indicated that maximal MGd concentrations of 1–2 μmol/kg occurred between 4 and 6 h after MGd infusion. Conclusion: Dose level 1 (2.9 mg/kg of MGd) is the recommended dose for combination with (RT) in phase II studies for locally advanced pancreatic and biliary cancers. Patient tolerance might be improved by modification of the RT schedule and antiemetic prophylaxis.     

吉西他滨联合奥沙利铂或顺铂治疗老年人晚期非小细胞肺癌的随机对照临床研究

背景与目的化疗可延长患者生存期，改善生活质量，是治疗晚期非小细胞肺癌的主要方法。对于70岁及以上的老年晚期非小细胞肺癌患者，治疗的毒副反应和治疗耐受性尤其重要。本研究的目的是观察比较吉西他滨联合奥沙利铂和吉西他滨联合顺铂治疗70岁及以上老年人晚期非小细胞肺癌的疗效和毒副反应。方法42例患者按随机表法分为GO组20例（吉西他滨1000mg／m^2，第1、8天；奥沙利铂65mg／m^2，第1、8天）和GP组22例（吉西他滨1000mg／m^2，第1、8天；顺铂30mg／m^2，第1～3天），28天为一周期，均治疗2周期以上。结果GO组CR1例，PR10例，SD7例，PD2例，有效率为55．0％；中位生存期为11．2月，1年生存率为45％。GP组PR9例，SD10例，PD3例，有效率为40．9％；中位生存期为11．8月，1年生存率为50％。两组有效率、中位生存期和1年生存率比较均无显著性差异（P均〉0．05）。毒副反应以白细胞降低和胃肠道反应为主，GP组Ⅲ＋Ⅳ度白细胞下降发生率和恶心呕吐发生率均显著高于GO组（17．4％VS4．8％，20．7％VS3．6％，P均〈0．05），GP组Ⅰ＋Ⅱ度脱发和肾功能异常发生率均显著高于GO组（43．5％ vs 10．7％，14．1％ vs 2．4％，P均〈0．05）。结论对于70岁及以上老年人晚期非小细胞肺癌，吉西他滨加奥沙利铂方案有较好的近期疗效，毒副反应轻，治疗耐受性好，临床应用更安全。     

Capecitabine and radiation therapy preceded and followed by combination chemotherapy in advanced pancreatic cancer

PURPOSE: The primary objective of this study was to evaluate the tolerance and toxicity of radiation therapy (RT) and capecitabine in patients with advanced, unresectable pancreatic carcinoma. To control micrometastatic disease, combination chemotherapy (gemcitabine and cisplatin) before and after combined modality therapy (CMT) was planned. METHODS AND MATERIALS: Patients with unresectable or metastatic pancreatic cancer were eligible. Gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 were administered on Days 1 and 8 of a 21-day cycle for two cycles. RT was then given to a dose of 50.4 Gy in 1.8 Gy fractions. Patients were treated with capecitabine 1330 mg/m2 daily during RT. After CMT, two additional cycles of gemcitabine and cisplatin completed the treatment. RESULTS: Twenty-three patients were treated. Eighteen patients completed CMT. One patient was removed from study during CMT for toxicity issues. Treatment delays and dose reductions were common during the final two cycles of gemcitabine and cisplatin as a result of myelosuppression. Median survival was 10.1 months (95% confidence interval [CI] = 7.6, 13.7) for all 23 patients and 12.8 months (95% CI = 8.2, 18.9) for 18 patients without metastasis. CONCLUSION: Combined modality therapy with RT and capecitabine was well tolerated. Chemotherapy after CMT was difficult to complete owing to cumulative myelosuppression. Survival, response, and toxicity were comparable to infusional 5-fluorouracil and RT.     

Phase I trial of gefitinib with concurrent radiotherapy and fixed 2-h gemcitabine infusion, in locally advanced pancreatic cancer

PURPOSE: Pancreatic cancers are resistant to radiotherapy (RT) and current chemotherapy agents. Epidermal growth factor receptor is overexpressed in pancreatic cancer, and in vitro studies have shown that epidermal growth factor receptor inhibitors can overcome radio- and chemoresistance. The aim of the study was to determine whether the addition of gefitinib to RT and gemcitabine for patients with locally advanced pancreatic carcinoma (LAPC) was feasible and safe. METHODS AND MATERIALS: Eighteen patients with pathologically proven LAPC, based on major vascular invasion based on helical computed tomography (CT) and endoscopic ultrasound, were entered into the study. The targeted irradiated volume included the tumor and 2-cm margin. Prophylactic irradiation of regional nodes was not allowed. Patients with >500 cm(3) of planning tumor volume were excluded. An initial cohort of 6 patients was treated with RT (45 Gy/25 fractions/5 weeks) plus concomitant gefitinib (250 mg/day). Successive cohorts of patients received 100, 150, and 200 mg/m(2)/day of gemcitabine in a 2-h infusion over Weeks 1, 2, 3, 4, and 5 with gefitinib (250 mg/day) and RT. Gefitinib was continued after RT until progression. A pharmacodynamic study of angiogenic markers was also performed to evaluate a possible antiangiogenic effect. RESULTS: There were no dose-limiting toxicities. Common toxicities were mild neutropenia, asthenia, diarrhea, cutaneous rash and nausea/vomiting. The median (95% confidence interval [CI]) progression-free survival was 3.7 (95% CI = 1.9-5.5) months, and the median overall survival was 7.5 (95% CI = 5.2-9.9) months. No significant reduction of vascular endothelial growth factor and interleukin-8 was observed after treatment. CONCLUSION: Our results support that the combination of gefitinib, RT, and gemcitabine has an acceptable toxicity but with modest activity in LAPC.     

奥沙利铂联合吉西他滨治疗晚期胰腺癌的临床观察

目的:观察奥沙利铂联合吉西他滨治疗晚期胰腺癌的疗效及不良反应。方法:经影像学诊断的晚期胰腺癌18例,使用奥沙利铂85mg/m2,静脉滴注2小时,第1、8天;吉西他滨835mg/m2,静脉滴注30分钟,第1、8天,21天为1周期,至少用2周期后评价疗效。结果:18例均可评价,获得CR1例,PR3例,总有效率22·2%(4/18)。主要不良反应为骨髓抑制、外周神经毒性及恶心呕吐,无化疗相关死亡。结论:奥沙利铂联合吉西他滨治疗晚期胰腺癌患者疗效较好,不良反应可以耐受,值得深入研究。     

吉西他滨联合顺铂双周方案与三周方案治疗晚期非小细胞肺癌的对比研究

目的研究对比吉西他滨(泽菲)联合顺铂双周方案与三周方案治疗晚期非小细胞肺癌的疗效及不良反应。方法双周方案组35例晚期非小细胞肺癌患者,给予吉西他滨1250mg/m2,d1,顺铂60mg/m2,d1,每14天重复,至少用4周期以上评价疗效。三周方案组32例患者,给予吉西他滨1000mg/m2,d1、d8,顺铂50mg/m2,d1、d2,每21天重复1次,至少用2周期以上评价疗效。结果67例均可评价疗效,双周方案组有效率48.6%(17/35),中位生存时间34.1周,1年生存率34.3%(12/35);三周方案组有效率43.7%(14/32),中位生存时间33.3周,1年生存率34.4%(11/32)。毒副反应方面,Ⅲ-Ⅳ度白细胞下降、Ⅲ-Ⅳ度血小板下降、Ⅲ-Ⅳ度恶心呕吐在双周方案组分别为8.6%、14.3%和5.7%,三周方案组分别为15.6%、18.8%和15.6%。结论吉西他滨(泽菲)联合顺铂双周方案与三周方案治疗非小细胞肺癌的疗效大致相等,双周方案不良反应明显减少。     

A phase II trial of gemcitabine plus capecitabine for patients with advanced pancreatic adenocarcinoma

Purpose While gemcitabine (GEM) is widely accepted for the treatment of advanced pancreatic cancer, capecitabine (CAP) has shown single agent activity and promising efficacy in combination with GEM. This phase II study was conducted to evaluate the efficacy and toxicity of GEM combined with dose escalated 14-day CAP as first-line chemotherapy for advanced pancreatic cancer. In addition, we also analyzed the correlation between CA19-9 response and clinical outcomes. Methods Patients had advanced pancreatic adenocarcinoma, no prior systemic chemotherapy other than that given concurrently with radiation therapy, at lease one measurable disease, and adequate organ functions. The patients were treated with GEM 1,000 mg/m² IV on days 1, 8 and CAP 1,000 mg/m² twice a day PO on days 1–14, in 21-day cycles. Results The objective RR among 45 patients was 40.0% (95% CI; 25.1–54.9), including 1CR (2.2%). The median TTP and OS were 5.4 months (95% CI; 1.8–9.0) and 10.4 months (95% CI; 6.2–14.5), respectively. Patients with ≥25% decline of serum CA19-9 had significantly better outcomes in terms of TTP and OS than those who did not (P < 0.03). The most frequent, grade 3–4, non-hematologic toxicity was hand–foot syndrome (6.7%). Conclusions The combination of GEM with dose escalated 14-day CAP is well tolerated and offers encouraging activity in the treatment of advanced pancreatic cancer. In addition, CA19-9 response correlates well with clinical outcomes in this population.