Prognostic value of CA 19-9 levels in patients with inoperable adenocarcinoma of the pancreas treated with gemcitabine

Serum carbohydrate antigen 19-9 (CA 19-9) has been identified as a useful tumour marker for diagnosis of exocrine pancreatic carcinoma, but its value for evaluating the response to chemotherapy with gemcitabine is not clear. Tumour regression in pancreatic carcinoma is hard to determine due to massive desmoplastic tissue. Furthermore, objective tumour response does not automatically transcribe into better survival. Therefore, clinical benefit response, a composed parameter consisting of factors like performance status, pain, and body weight was integrated in evaluating tumour response. The aim of this prospective study was to evaluate the usefulness of serial CA 19-9 measurements as a biochemical response marker and an outcome prognostic parameter in patients with advanced pancreatic cancer receiving gemcitabine treatment. A total of 46 consecutive patients (median age 66 years) suffering from histologically proven locally advanced or metastatic adenocarcinoma of the exocrine pancreas were analysed. Gemcitabine was applied for a median of 23 courses (range 6-76). Two patients achieved an objective complete remission, five an objective partial remission (overall response, OR=15.2%), while objective stable disease was documented in 19 and objective progressive disease in 20 patients. Patients with a decrease of >20% of the baseline CA 19-9 level after 8 weeks of chemotherapy had a significantly better median survival than patients with a rise or a decline <20%. The response of CA 19-9 >20% during chemotherapy was the only independent predictor of survival in a multivariate analyses. In contrast, neither objective tumour response nor clinical benefit response showed this level of significance. In conclusion, kinetics of CA19-9 serum concentration serves as an early indicator of response to gemcitabine chemotherapy in advanced pancreatic cancer.     

Clinical features of long time survivors with unresectable pancreatic cancer treated by gemcitabine alone

The objective of this study was to clarify the clinical features of long-time survivors with unresectable pancreatic cancer treated by gemcitabine (GEM) alone and to predict survival time after the first course of treatment. Eighteen consecutive patients (median age 65.3 years, range 49-77 years; 12 males, 6 females) with unresectable pancreatic cancer and a baseline Karnofsky's performance state = or >60 were treated with GEM in a dose of 1,000 mg/m(2) weekly x 3 followed by 1 week of rest until progression. The overall response rate was 0% (CR 0, PR 0, SD 11 cases, and PD 5 cases), and the median survival time (MST) was 268 days. We observed a statistically significant difference in the patients with or without liver metastasis at the start of treatment (131.6 vs 324.9 days; p=0.0045). We also evaluated the usefulness of serial CA 19-9 measurements as a biochemical response marker and an outcome prognostic parameter in patients with unresectable pancreatic cancer receiving GEM alone. We classified two subgroups into responders (patients with a decrease of = or >10% of the baseline CA 19-9 level after 4 weeks of chemotherapy) and non-responder (patients with a increase of the baseline CA 19-9 level or with a decrease of <10% of the baseline CA 19-9 level after 4 weeks of chemotherapy). Responder had a significantly better median survival than non-responders (416.6 vs 138.3 days; p=0.009). In conclusion, CA 19-9 serum concentration serves as an early indicator of response to chemotherapy with GEM alone in unresectable pancreatic cancer.     

Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate.

PURPOSE: This phase III, randomized, open-label, multicenter study compared the overall survival associated with irinotecan plus gemcitabine (IRINOGEM) versus gemcitabine monotherapy (GEM) in patients with chemotherapy-naive, locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: IRINOGEM patients received starting doses of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 given weekly for 2 weeks every 3-week cycle. GEM patients received gemcitabine 1,000 mg/m2 weekly for 7 of 8 weeks (induction) and then weekly for 3 of 4 weeks. The primary end point of the trial was survival. Secondary end points included tumor response, time to tumor progression (TTP), changes in CA 19-9, and safety. RESULTS: In each arm, 180 randomly assigned patients comprised the intent-to-treat population evaluated for efficacy; 173 IRINOGEM and 169 GEM patients were treated. Median survival times were 6.3 months for IRINOGEM (95% CI, 4.7 to 7.5 months) and 6.6 months for GEM (95% CI, 5.2 to 7.8 months; log-rank P =.789). Tumor response rates were 16.1% (95% CI, 11.1% to 22.3%) for IRINOGEM and 4.4% (95% CI, 1.9% to 8.6%) for GEM (chi2 P <.001). Median TTP was 3.5 months for IRINOGEM versus 3.0 months for GEM (log-rank P =.352). However, subset analyses in patients with locally advanced disease suggested a TTP advantage with IRINOGEM versus GEM (median, 7.7 v 3.9 months). CA 19-9 progression was positively correlated with tumor progression. The incidence of grade 3 diarrhea was higher in the IRINOGEM group but grade 3 to 4 hematologic toxicities and quality-of-life outcomes were similar. CONCLUSION: IRINOGEM safely improved the tumor response rate compared with GEM but did not alter overall survival.     

Gemcitabine in advanced pancreatic cancer: a phase II trial

The 5-year survival for pancreatic cancer is usually less than 5%, and no treatment has demonstrated consistent effect on patient survival and disease-related symptoms. Early studies with gemcitabine suggested a modest antitumor activity with significant improvement in disease-related symptoms. This phase II study reports the activity of gemcitabine on 33 consecutive patients with unresectable pancreatic carcinoma. Twenty-three patients had metastatic and 10 locally advanced unresectable disease. Twenty-six patients had not received any previous treatment and seven had received first-line chemotherapy with 5-fluorouracil. Gemcitabine 1,000 mg/m2 was administered intravenously in 30 minutes in the first cycle once weekly for up to 7 weeks followed by 1 week rest; then in subsequent cycles, once weekly for 3 of every 4-week cycle. Four patients obtained partial response (12%). Fifteen patients (45%) had stable disease with a median duration of 32 weeks (range: 16-75 weeks), and 14 patients experienced progressive disease. Median duration of response was 34.5 weeks (range: 19-50 weeks). Median survival was 33 weeks (range: 2-91 weeks). All 4 responding patients and 14 of 15 (93%) patients with stable disease had improvement in performance status and decrease in daily analgesic requirement. Toxicity was mild and mainly consisted of moderate and rapidly reversible myelosuppression. We conclude that gemcitabine chemotherapy was very well tolerated and determined a significant clinical improvement with modest antitumoral activity in patients with advanced pancreatic cancer.     

Assessing prognosis in metastatic pancreatic cancer by the serum tumor marker CA 19-9: pretreatment levels or kinetics during chemotherapy?

BACKGROUND: The carbohydrate antigen 19-9 (CA 19-9) is currently the most widely used serum tumor marker in pancreatic cancer (PC). CA 19-9 pretreatment levels as well as CA 19-9 kinetics during systemic chemotherapy can provide prognostic information regarding survival of patients with metastatic PC. CASE REPORTS: We report the clinical course of 2 patients with metastatic PC who underwent palliative chemotherapy with gemcitabine. Both patients showed a significant elevation of pretreatment CA 19-9 levels (7,505 and 150,000 U/ml, respectively), however, subsequently they experienced a highly significant reduction (>90%) of CA 19-9 kinetics under gemcitabine chemotherapy. A good disease control and a clinical benefit response were achieved in both patients. Time to tumor progression was 30 weeks and 28 weeks, overall survival 14 months and 11 months, respectively. CONCLUSION: These data indicate that CA 19-9 kinetics under chemotherapy may possibly serve as a useful surrogate marker for time to tumor progression and survival in advanced PC.     

Phase II study of gemcitabine combined with uracil-tegafur in metastatic pancreatic cancer

OBJECTIVE: The single agent gemcitabine is the standard first-line treatment for advanced pancreatic cancer. Recent studies of a combination of gemcitabine and 5-fluorouracil (5-FU) revealed that survival data were superior to those with gemcitabine or 5-FU alone. The administration of oral uracil-tegafur (UFT) is more convenient and simulates the effect of a continuous or protracted infusion of 5-FU. Therefore, we conducted a phase II study of gemcitabine combined with UFT in metastatic pancreatic cancer patients and assessed the efficacy and the toxicity of the regimen. METHODS: Twenty-two pancreatic adenocarcinoma patients (18 males, 4 females) were enrolled from December 2000 to September 2002. The regimen consisted of gemcitabine 1,000 mg/m(2) once weekly for 3 consecutive weeks, and oral UFT 390 mg/m(2)/day (in 3 divided doses) on days 1-14. The cycle was repeated every 28 days. The objective tumor response was evaluated after 2 courses of chemotherapy. RESULTS: 82 cycles were administered in total, with a median of 3 cycles per patient (range 1-6 cycles). The median age was 52 years (range 28-69 years). Response to treatment could be assessed in all patients. The objective response rate was 22.7% (95% CI, 7.8-45.4) with no complete response and 5 partial responses. Four patients (18.2%) had stable disease and 13 patients (59.1%) had a progression. The median time to progression was 4.2 months (range 0.9-13.6). The median overall survival was 5.8 months (range 0.5-13.6). Of 10 patients eligible for the assessment of clinical benefit response, 4 (40%, 95% CI 12.2-73.8) showed clinical benefit. Among 21 patients with baseline CA 19-9 levels, CA 19-9 was reduced by 50% or more in 12 patients (57.1%). The chemotherapy was generally well tolerated and the most common grade 3-4 toxic side effects were neutropenia (18.2%), anemia (4.5%), and diarrhea (4.5%). CONCLUSIONS: The combination chemotherapy with gemcitabine and UFT in metastatic pancreatic cancer was tolerable for most patients but showed modest response rates and clinical benefit. However, a randomized phase III study should be conducted in order to further test the efficacy of the regimen.     

Which is the best monitoring study (tumor marker, computed tomography or 18F-fluoro-2-deoxy-D-glucose positron emission tomography) to evaluate efficacy of chemotherapy on unresectable pancreatic cancer ?

The objective of this study was to clarify the clinical features of long-time survivors with unresectable pancreatic cancer treated by gemcitabine(GEM)alone and to predict survival time by carbohydrate antigen(CA)19-9, enhanced computed tomography(CT), and 18F-fluoro-2-deoxy-D-glucose positron emission tomography(FDG-PET) in monitoring the response to chemotherapy. Twenty-one patients with unresectable pancreatic cancer were enrolled in this study. All patients were evaluated by serum CA19-9 level, tumor size of CT, maximum standardized uptake value (SUVmax)with FDG-PET and other factors before chemotherapy(GEM alone at a dose of 1,000 mg/m(2) weekly x 3 followed by 1 week of rest), and they received chemotherapy until obviously progressive disease. Serum CA19-9, tumor size of CT and SUVmax with PET were measured after three courses of chemotherapy in ten patients. We compared these three modalities in terms of two points: Which is the best modality to predict survival time ? Which is the best monitoring modality to evaluate the efficacy of chemotherapy on unresectable pancreatic cancer ? A significant difference in survival time was not found between high level group and low level group of serum CA19-9 level and SUVmax with FDG-PET and also longest length of tumor by enhanced CT. In ten patients we evaluated the response rate of each parameter CA19-9(IU/mL), CT(longest length of tumor), and SUVmax with FDG-PET. We defined the response rate(pretreatment level of CA19-9 or longest length of tumor or SUVmax-after 3 courses chemotherapy level of CA19-9 or longest length of tumor or SUVmax/pretreatment level of CA19-9 or longest length of tumor or SUVmax). Response rate of CA19-9 was significantly correlated with survival time(r=0.633, p=0.0481). However, the response rate of SUVmax with FDG-PET had no significant correlation with survival time(r=0.019, p=0.9630). In the present study, the response rate of CA19-9 is the best monitoring modality to evaluate the efficacy of chemotherapy.     

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial.

PURPOSE: To determine the response rate, time to disease progression, survival duration and rate, and toxicity with the combination of cetuximab and gemcitabine in patients with epidermal growth factor receptor (EGFR)-expressing advanced pancreatic cancer. PATIENTS AND METHODS: Patients with measurable locally advanced or metastatic pancreatic cancer who had never received chemotherapy for their advanced disease and had immunohistochemical evidence of EGFR expression were eligible for the multicenter phase II trial. Patients were treated with cetuximab at an initial dose of 400 mg/m(2), followed by 250 mg/m(2) weekly for 7 weeks. Gemcitabine was administered at 1,000 mg/m(2) for 7 weeks, followed by 1 week of rest. In subsequent cycles, cetuximab was administered weekly, and gemcitabine was administered weekly for 3 weeks every 4 weeks. RESULTS: Sixty-one patients were screened for EGFR expression, 58 patients (95%) had at least 1+ staining, and 41 were enrolled onto the trial. Five patients (12.2%) achieved a partial response, and 26 (63.4%) had stable disease. The median time to disease progression was 3.8 months, and the median overall survival duration was 7.1 months. One-year progression-free survival and overall survival rates were 12% and 31.7%, respectively. The most frequently reported grade 3 or 4 adverse events were neutropenia (39.0%), asthenia (22.0%), abdominal pain (22.0%), and thrombocytopenia (17.1%). CONCLUSION: Cetuximab in combination with gemcitabine showed promising activity against advanced pancreatic cancer. Further clinical investigation is warranted.     

CA 19-9 and Survival in Advanced and Unresectable Pancreatic Adenocarcinoma and Cholangiocarcinoma

Background

The CA 19-9 tumour marker is increasingly used to monitor response to therapy in patients with pancreatic adenocarcinoma. Serum CA 19-9 levels have also been shown to correlate with survival. However, their role in cholangiocarcinoma is less clear.

Aim of study

To assess the utility of CA 19-9 levels in the management of patients with advanced pancreatic adenocarcinoma or cholangiocarcinoma in routine clinical practice is the aim of the study.

Methods

A retrospective analysis of CA 19-9 values and survival was performed in 26 patients with pancreatic adenocarcinoma receiving gemcitabine and in 18 patients with cholangiocarcinoma.

Results

Patients with advanced pancreatic adenocarcinoma receiving gemcitabine who experienced a decrease of ≥20% in CA 19-9 concentration had a median survival of 13.9+ months (range 4.2–23.5) compared to 7.6+ months (range 4.0–14.7) in those without such a change (p?=?0.0109). In patients with advanced cholangiocarcinoma, the median survival was longest in those with a baseline CA 19-9 level of less than 1,000 U/ml; 11.8 months (range 1.0–41.4) vs 6.2 months (range 3.1–9.4; p?=?0.0075).

Conclusions

The CA 19-9 concentration has a valuable role in predicting outcome in patients with pancreatic adenocarcinoma and cholangiocarcinoma. It is helpful in guiding therapy and should be used accordingly in oncology practice.     

A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer

This study investigated the maximum-tolerated dose of gemcitabine based on the frequency of dose-limiting toxicities of weekly gemcitabine treatment with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Fifteen patients with locally advanced pancreatic cancer that was histologically confirmed as adenocarcinoma were enrolled in this phase I trial of weekly gemcitabine (150-350 mg x m(-2)) with concurrent radiotherapy (50.4 Gy in 28 fractions). Gemcitabine was administered weekly as an intravenous 30-min infusion before radiotherapy for 6 weeks. Three of six patients at the dose of 350 mg x m(-2) of gemicitabine demonstrated dose-limiting toxicities involving neutropenia/ leukocytopenia and elevated transaminase, while nine patients at doses of 150 mg x m(-2) and 250 mg x m(-2) did not demonstrate any sign of dose-limiting toxicity. Of all 15 enrolled patients, six patients (40.0%) showed a partial response. More than 50% reduction of serum carbohydrate antigen 19-9 level was observed in 13 (92.9%) of 14 patients who had pretreatment carbohydrate antigen 19-9 levels of 100 U x ml(-1) or greater. The maximum-tolerated dose of weekly gemcitabine with concurrent radiotherapy was 250 mg x m(-2), and this regimen may have substantial antitumour activity for patients with locally advanced pancreatic cancer. A phase II trial of weekly gemcitabine at the dose of 250 mg x m(-2) with concurrent radiation in patients with locally advanced pancreatic cancer is now underway.     

Carbohydrate antigen 19‐9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine‐containing chemotherapy

BACKGROUND:

Carbohydrate antigen 19‐9 (CA19‐9) is a widely used biomarker in pancreatic cancer. There is no consensus on the interpretation of the change in CA19‐9 serum levels and its role in the clinical management of patients with pancreatic cancer.

METHODS:

Individual patient data from 6 prospective trials evaluating gemcitabine‐containing regimens from 3 different institutions were pooled. CA19‐9 values were obtained at baseline and after successive cycles of treatment. The objective of this study was to correlate a decline in CA19‐9 with outcomes while undergoing treatment.

RESULTS:

A total of 212 patients with locally advanced (n = 50) or metastatic (n = 162) adenocarcinoma of the pancreas were included. Median baseline CA19‐9 level was 1077 ng/mL (range, 15‐492,241 ng/mL). Groups were divided into those levels below (low) or above (high) the median. Median overall survival (mOS) was 8.7 versus 5.2 months (P = .0018) and median time to progression (mTTP) was 5.8 versus 3.7 months (P = .082) in the low versus high groups, respectively. After 2 cycles of chemotherapy, up to a 5% increase versus ≥ 5% increase in CA19‐9 levels conferred an improved mOS (10.3 vs 5.1 months, P = .0022) and mTTP (7.5 vs 3.5 months, P = 0.0005).

CONCLUSIONS:

In patients who have advanced pancreatic cancer treated with gemcitabine‐containing regimens baseline CA19‐9 is prognostic for outcome. A decline in CA19‐9 after the second cycle of chemotherapy is not predictive of improved mOS or mTTP; thus, CA19‐9 decline is not a useful surrogate endpoint in clinical trials. Clinically, a ≥ 5% rise in CA19‐9 after 2 cycles of chemotherapy serves as a negative predictive marker. Cancer 2013. © 2012 American Cancer Society.     

Weekly full-dose gemcitabine and single-dose cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer

The aim of this study was to evaluate the efficacy and the toxicity of a full dose of gemcitabine and a single dose of cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Forty-one patients with locally advanced pancreatic cancer were enrolled. Patients received gemcitabine (1000 mg m(-2) on days 1, 8, 15, 29, and 36) and cisplatin (70 mg m(-2) on days 1 and 29) with concurrent radiotherapy (45 Gy in 25 fractions). Treatment was completed in 38 out of 41 patients (92.7%). The overall response rate was 24.4% (two complete and eight partial). Six patients (14.6%) underwent definite pancreatic resection and four had negative surgical margins. The intention of the treatment analysis showed that the median survival time and median time to tumour progression were 16.7 and 8.9 months. The 1- and 2-year survival rates were 63.3 and 27.9%, respectively. Overall survival was significantly longer in the low baseline CA19-9 group and therapeutic responders. Toxicities were tolerable and successfully managed by conservative treatments. The therapeutic scheme of a weekly full dose of gemcitabine and a single dose of cisplatin combined with external radiation is effective and might prolong the survival of patients with locally advanced pancreatic cancer.     

A resected case of effective treatment with gemcitabine for advanced pancreatic cancer with peritoneal metastasis

We report a resected case of advanced pancreatic cancer after successful chemotherapy. A 69-year-old man with abdominal pain was diagnosed as locally advanced pancreatic tail cancer with peritoneal metastasis based on computed tomography (CT). Preoperative serum CA 19-9 was 5,046 U/mL. In the outpatient setting, gemcitabine (GEM) at a dose of 1,000 mg/m(2)was administered once a week for 3 weeks with a 1-week rest as 1 cycle. Abdominal CT scan after 5 cycles of chemotherapy revealed that ascites disappeared and the tumor dramatically shrank. Serum CA 19-9 also dropped to 12 U/mL. Thus, we considered the patient had a partial response, and performed distal pancreatectomy and splenectomy with D 3 lymph node dissection. Peritoneal seeding was not found and peritoneal washing cytology was negative. Histological examination of the primary lesion revealed a small amount of residual cancer cells. However, he died of peritoneal metastasis only 3 months after the operation. Surgical resection following chemotherapy should be performed carefully after close evaluation of the antitumor efficacy including residual isolated tumor cell for patients with previously distant metastases.     

血清CA19-9预测吉西他滨化疗的晚期胰腺癌患者的预后

目的:将晚期胰腺癌化疗前后血清癌抗原19-9(CA19-9)变化水平与其影像学客观反应和临床受益反应进行比较,以探讨与预后关系最密切的因素。方法:比较血清CA19-9下降水平与影像学客观反应和临床受益反应作为判定晚期胰腺癌患者接受吉西他滨单药或以其为基础的联合方案化疗后生存期的差异。结果:所有64例患者的中位生存期(median survival time,MST)为7.0个月。血清CA19-9基线水平小于中位值(928.6ng/ml)患者的生存期明显长于其水平大于中位值者(9.4个月vs 4.2个月,P<0.001)血清CA19-9下降水平与MST和疾病无进展(non-progression disease,NPD)及临床受益反应(clinical benefit response,CBR)密切相关,化疗2周期后血清CA19-9下降水平≥25%的MST明显长于其水平下降<25%者(8.9个月vs 4.4个月,P<0.001)。影像学疾病无进展(NPD)和临床受益(CBR)均与MST密切相关,NPD患者的MST明显长于疾病进展者(8.8个月vs 7.4个月,P=0.022);CBR患者的MST明显长于非CBR者(9.1个月vs 6.2个月,P=0.022)。多因素分析显示,血清CA19-9基线水平的中位值和血清CA19-9下降水平≥25%是影响预后的独立因素生存期密切相关,而NPD和CBR与预后无关。结论:与影像学客观反应和临床受益反应相比,血清CA19-9下降水平能更有力地预测预后生存期。血清CA19-9下降水平是指导临床治疗晚期胰腺癌较合理的指标。     

A patient with pancreatic cancer and multiple liver metastases after total pancreatectomy who showed a partial response to combination chemotherapy with gemcitabine and UFT

A 69-year-old man underwent a complete pancreatectomy in March 2002 because of cancer of the body of the pancreas. Two months after surgery, the patient had multiple metastases to the liver, abdominal recurrence, and an elevated cancer antigen (CA) 19-9 level. Combination chemotherapy with gemcitabine and UFT was administered on an outpatient basis. Chemotherapy consisted of biweekly gemcitabine (1,000 mg/m(2)) and daily UFT (300 mg). After 3 months of treatment, a computed tomographic scan of the liver showed marked shrinkage of metastatic lesions, accompanied by a decrease in the CA19-9 level. The patient spent most of his time at home and worked as usual; his quality of life was maintained. The only adverse event was transient leukopenia (grade 2). He died of peritoneal dissemination in August 2003 (15 months after recurrence). Our experience suggests that combination chemotherapy with gemcitabine and UFT may promote tumor dormancy and relieve symptoms in patients with liver metastasis after surgery for pancreatic cancer or with recurrence of metastasis.     

血清CA19-9水平检测对吉西他滨方案化疗晚期胰腺癌患者预后的临床预测

背景与目的：吉西他滨是晚期胰腺癌化疗最有效的药物之一。CA19-9对胰腺癌诊断、判断手术疗效及检测术后复发等具有较为肯定的临床价值。本研究通过检测接受含吉西他滨方案化疗的晚期胰腺癌患者化疗前后血清CA19-9的动态水平，分析血清CA19-9水平与化疗疗效及生存的关系。方法：选取中山大学肿瘤防治中心收治的71例经病理学证实的不能手术切除的局部晚期和（或）伴有远处转移的胰腺癌患者，KPS评分≥70，一线接受吉西他滨单药或以吉西他滨为基础的联合方案化疗，化疗前后进行血清CA19-9的动态测定。结果：71例患者中10例（14．1％）血清CA19-9基线水平在正常范围内，61例（85．9％）有不同程度的升高，两组患者的总生存时间分别为9．0个月和7．9个月。差异无统计学意义（P=0．797）。基线CA19-9升高的61例患者中位基线CA19-9水平为682U／mL，基线CA19-9低于中位值的患者总生存时间显著长于高于中位值者（9．6个月和5．1个月，P=0．001）；两组影像学客观有效率和临床获益率相比均未达到统计学意义（P〈0．05）。化疗后CA19-9下降大于25％的患者总生存时间显著长于CA19-9无下降或下降小于25％的患者．分别为10．2个月和5．0个月，影像学客观有效率分别为47．8％和10．5％，临床获益率分别为69．2％和8．0％，差异均有显著性（P〈0．01）。多因素分析显示，对于基线CA19-9高于正常的患者，化疗前基线CA19-9水平、化疗后CA19-9下降率及肿瘤细胞分化程度是预测接受含吉西他滨方案化疗的晚期胰腺癌患者生存的独立危险因素。结论：对于基线血清CA19-9水平升高的晚期胰腺癌患者，接受含吉西他滨方案化疗时．化疗前CA19-9升高的水平和化疗后下降的比率可以预测晚期胰腺癌患者的预后。     

Estimating prognosis and palliation based on tumour marker CA 19-9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy

Background:

To investigate the prognostic value of quality of life (QOL) relative to tumour marker carbohydrate antigen (CA) 19-9, and the role of CA 19-9 in estimating palliation in patients with advanced pancreatic cancer receiving chemotherapy.

Methods:

CA 19-9 serum concentration was measured at baseline and every 3 weeks in a phase III trial (SAKK 44/00–CECOG/PAN.1.3.001). Patients scored QOL indicators at baseline, and before each administration of chemotherapy (weekly or bi-weekly) for 24 weeks or until progression. Prognostic factors were investigated by Cox models, QOL during chemotherapy by mixed-effect models.

Results:

Patient-rated pain (P<0.02) and tiredness (P<0.03) were independent predictors for survival, although less prognostic than CA 19-9 (P<0.001). Baseline CA 19-9 did not predict QOL during chemotherapy, except for a marginal effect on pain (P<0.05). Mean changes in physical domains across the whole observation period were marginally correlated with the maximum CA 19-9 decrease. Patients in a better health status reported the most improvement in QOL within 20 days before maximum CA 19-9 decrease. They indicated substantially less pain and better physical well-being, already, early on during chemotherapy with a maximum CA 19-9 decrease of ⩾50% vs <50%.

Conclusion:

In advanced pancreatic cancer, pain and tiredness are independent prognostic factors for survival, although less prognostic than CA 19-9. Quality of life improves before best CA 19-9 response but the maximum CA 19-9 decrease has no impact on subsequent QOL. To estimate palliation by chemotherapy, patient''s perception needs to be taken into account.     

Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer.

PURPOSE: This phase II, multicenter, open-label, single-arm study evaluated the efficacy and safety of irinotecan and gemcitabine as combination chemotherapy for previously untreated patients with unresectable or metastatic pancreatic cancer. PATIENTS AND METHODS: Patients received repeated 21-day cycles at starting doses of gemcitabine 1,000 mg/m(2) over 30 minutes followed immediately by irinotecan 100 mg/m(2) over 90 minutes, both given intravenously on days 1 and 8. Patients were evaluated for objective tumor response, changes in the serum tumor marker CA 19-9, time to tumor progression (TTP), survival, and safety. RESULTS: Forty-five patients were treated. Eleven patients (24%) had 50% or greater reductions in tumor area. These were confirmed one cycle later in nine patients (response rate, 20%; 95% confidence interval, 8% to 32%). Among 44 patients with baseline CA 19-9 determinations, CA 19-9 decreased during therapy in 22 patients (50%) and was reduced by 50% or more in 13 patients (30%). Median TTP was 2.8 months (range, 0.3 to 10.8 months). There were significant (P <.001) correlations between proportional changes in CA 19-9 and radiographic changes in tumor area with regard to extent of change (r =.67), timing of minimum on-study values (r =.85), and tumor progression (r =.89). Median survival was 5.7 months (range, 0.4 to 19.4+ months), and the 1-year survival rate was 27%. Severe toxicities were uncommon and primarily limited to grade 4 neutropenia (2%), grade 4 vomiting (2%), and grade 3 diarrhea (7%). CONCLUSION: Irinotecan/gemcitabine is a new combination that offers encouraging activity in terms of radiographic and CA 19-9 response and notable 1-year survival in pancreatic cancer. The regimen was well tolerated, with minimal grade 3 and 4 toxicities and excellent maintenance of planned dose-intensity.     

Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial.

BACKGROUND: A standard second-line chemotherapy regimen has yet to be defined for patients with gemcitabine (Gem)-refractory advanced pancreatic cancer (PC). PATIENTS AND METHODS: In this multicenter phase II trial, patients with unresectable or metastatic PC who had progressed on single-agent Gem or a Gem-containing regimen received pemetrexed 500 mg/m(2) as a 10-min infusion every 3 weeks until disease progression or occurrence of unacceptable toxicity. The primary end point was the 3-month survival rate. RESULTS: A total of 192 treatment cycles were given to 52 patients. The overall response rate was 3.8% (two partial responses); 10 patients (19.2%) experienced stable disease, nine of them for >12 weeks. At least one CA 19-9 reduction > or =50% occurred in 12 patients (23.1%). The 3-month survival rate was 75% (95% confidence interval 63.2% to 86.8%), the median time to tumor progression was 7 weeks (range 1-62 weeks) and the median overall survival time was 20 weeks (range 1-84 weeks). Grade 3/4 hematological toxic effects included (percent of patients): neutropenia (17.3%), thrombocytopenia (5.8%) and anemia (3.8%). The most frequent non-hematological toxic effects were diarrhea, nausea and stomatitis/pharyngitis (23.1% each). CONCLUSION: Pemetrexed is a safe treatment option with moderate activity in patients with advanced PC after failure of Gem.     

血清CA19-9预测吉西他滨化疗的晚期胰腺癌患者的预后

目的：将晚期胰腺癌化疗前后血清癌抗原19-9（CA19-9）变化水平与其影像学客观反应和临床受益反应进行比较,以探讨与预后关系最密切的因素。方法：比较血清CA19-9下降水平与影像学客观反应和临床受益反应作为判定晚期胰腺癌患者接受吉西他滨单药或以其为基础的联合方案化疗后生存期的差异。结果：所有64例患者的中位生存期（median survival time,MST）为7.0个月。血清CA19-9基线水平小于中位值（928.6ng/ml）患者的生存期明显长于其水平大于中位值者（9.4个月vs 4.2个月,P〈0.001）血清CA19-9下降水平与MST和疾病无进展（non-progression disease,NPD）及临床受益反应（clinical benefit response,CBR）密切相关,化疗2周期后血清CA19-9下降水平≥25%的MST明显长于其水平下降〈25%者（8.9个月vs 4.4个月,P〈0.001）。影像学疾病无进展（NPD）和临床受益（CBR）均与MST密切相关,NPD患者的MST明显长于疾病进展者（8.8个月vs 7.4个月,P=0.022）;CBR患者的MST明显长于非CBR者（9.1个月vs 6.2个月,P=0.022）。多因素分析显示,血清CA19-9基线水平的中位值和血清CA19-9下降水平≥25%是影响预后的独立因素生存期密切相关,而NPD和CBR与预后无关。结论：与影像学客观反应和临床受益反应相比,血清CA19-9下降水平能更有力地预测预后生存期。血清CA19-9下降水平是指导临床治疗晚期胰腺癌较合理的指标。