Prognostic Factors in Patients with Advanced Pancreatic Cancer Treated with Gemcitabine Chemotherapy: Clinical Characteristics of Long-term Survivors

Sung Gyu An; Dong Uk Kim; Geun Am Song; Ae Lee Jang

doi:10.4166/kjg.2014.64.6.356

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An, Kim, Song, and Jang: Prognostic Factors in Patients with Advanced Pancreatic Cancer Treated with Gemcitabine Chemotherapy: Clinical Characteristics of Long-term Survivors

Original Article

Korean J Gastroenterol 2014;64(6):356-363.

Published online: 4 October 2014

DOI: https://doi.org/10.4166/kjg.2014.64.6.356

Prognostic Factors in Patients with Advanced Pancreatic Cancer Treated with Gemcitabine Chemotherapy: Clinical Characteristics of Long-term Survivors

Sung Gyu An, Dong Uk Kim, Geun Am Song, Ae Lee Jang¹

Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea

¹Department of Nursing Science, College of Health Sciences, Youngsan University, Yangsan, Korea

Correspondence to: Dong Uk Kim, Department of Internal Medicine, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Korea. Tel: +82-51- 240-7869, Fax: +82-51-244-8180, E-mail: amlm3@hanmail.net

Received 12 September 201425 October 2014 Accepted 25 October 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

Gemcitabine-based chemotherapy has been used as a standard treatment in patients with unresectable pancreatic cancer. However, the clinical outcomes of this regimen are still unsatisfactory in prolonging survival. We retrospectively analyzed clinical characteristics of patients with advanced pancreatic cancers who received gemcitabine-based chemotherapy and showed long-term survival.

Methods

We enrolled 49 patients who underwent treatment with more than three cycles of gemcitabine-based chemotherapy. Long-term survivor was defined as patient who has survived more than 12 months after diagnosis. The clinical characteristics were analyzed to compare the differences between long-term and short-term survivors. Univariate or multivariate analyses were performed to identify prognostic factors associated with chemo-responses.

Results

Twenty patients (41%) survived more than 12 months. Long-term survivors had smaller tumor size (OR 2.190, p=0.049, 95% CI 1.005-4.773) and higher serum BUN level (OR 0.833, p=0.039, 95% CI 0.701-0.990) compared to short-term survivors. Overall median and progression-free survivals were 11 and 4 months, respectively. Presence of distant metastasis (hazard ratio 1.441, p=0.035, 95% CI 1.002-2.908) was a significant independent predictor of progression-free survival. Tumor size (hazard ratio 1.534, p=0.004, 95% CI 1.150-2.045) was associated with overall survival.

Conclusions

Gemcitabine chemotherapy may be more effective and allow longer survivals in patients with clinical characters of smaller tumor size and normal serum BUN level at diagnosis. We suggest a well-designed large controlled study to evaluate the prognostic factors such as clinical characteristics and molecular biological features in patients with advanced pancreatic cancers who receive gemcitabine-based chemotherapy.

Keywords: Pancreatic cancer, Gemcitabine, Long-term survival, Prognostic factor

References

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Fig. 1.

Consort algorithm of patient selection. We enrolled 49 patients who underwent more than three cycles of gemcitabine-based chemotherapy without radiation therapy and received regular follow up. CTx, chemotheraphy.

Fig. 2.

Progression free survival (PFS) curves according to the presence of distant metastasis (A) and overall survival (OS) curves according to the tumor size (B) in patients with advanced pancreatic cancers who received gemcitabine-based chemotherapy. Distant metastasis (hazard ratio 1.441, p=0.035, 95% CI 1.002-2.908) and tumor size (hazard ratio 1.534, p=0.004, 95% CI 1.150-2.045) were related to PFS and OS, respectively.

Table 1.

Baseline Characteristics of Patients with Pancreatic Cancer

Characteristic	Value
Age (yr)	61.3±9.6
Male	29 (59)
Laboratory findings
WBC (10³/µL)	6,580 (4,935-7,565)
Hemoglobin (g/dL)	12.2 (11.0-13.75)
Platelet (10³/µL)	204 (154–271)
Albumin (mg/dL)	3.9 (3.5-4.2)
BUN (mg/dL)	12.1 (9.4-15.3)
Creatinine (mg/dL)	0.78 (0.62-0.90)
Total bilirubin (mg/dL)	0.94 (0.56-1.48)
Tumor markers
CEA (ng/mL)	8.56 (0.30-86.65)
CA 19-9 (U/mL)	291 (52.6-3,234.0)
Tumor size (cm)	3.8±1.4
Chemotherapy regimen
Gemcitabine mono	29 (59.2)
Combination	20 (40.8)
With cisplatin	2 (4.1)
With erlotinib	10 (20.4)
With capecitabine	8 (16.3)
Location of tumor
Head	27 (55.1)
Body-tail	22 (44.9)
Calcinomatosis peritonei	4 (8.2)
Distant metastasis	25 (51.0)
Response at 12 weeks after chemotherapy
PD	23 (46.9)
SD	23 (46.9)
PR	3 (6.1)
CA 19-9 (U/mL) at 12 weeks after chemotherapy	400 (29.5-4,126.0)
Initial CA 19-9/CA 19-9 at 12 weeks after chemotherapy	1.35±1.70
Survival (mo)
Progression free survival	4 (3.0-7.5)
Overall survival	11 (5.7-15.3)

Values are presented as mean±SD, n (%), or median (interquartile range). WBC, white blood cell; PD, progressive disease; SD, stable disease; PR, partial response.

Table 2.

Factors Influencing Survival at One Year on Univariate Analysis

Variable	Below one year on overall survival (n=29)	More than one year on overall survival (n=20)	p-value
Overall survival (mo)	10.57±1.96	60.35±3.18	0.569
Sex (male)	17 (58.6)	12 (60.0)	0.923
Laboratory finding
Hemoglobin (g/dL)	1.80±0.33	1.67±0.37	0.416
Albumin (mg/dL)	3.73±0.56	3.97±0.61	0.171
INR (prothrombin time ratio)	1.04±0.08	1.03±0.08	0.791
BUN (mg/dL)	11.42±5.26	15.29±7.17	0.034
Creatinine (mg/dL)	0.76±0.28	0.84±0.18	0.270
Total bilirubin (mg/dL)	3.60±6.15	1.57±2.30	0.113
CEA (ng/mL)	11.82±20.97	4.61±4.21	0.120
CA 19-9 (U/mL)	6,534.77±12,908.96	832.52±1,351.72	0.034
Tumor size (cm)	4.169±1.503	3.3±1.103	0.044
Tumor location (body or tail)	11 (38)	11 (55)	0.238
Carcinomatosis peritonei (yes)	4 (14)	0	0.083
Distant metastasis (yes)	18 (62)	7 (35)	0.062
Chemotherapy regimen (combination)	10 (35)	10 (50)	0.277
Response at 12 weeks after chemotherapy
PD	14 (58)	4 (20)	0.036
SD	9 (38)	14 (70)
PR	1 (4)	2 (10)
CA 19-9 (U/mL) at 12 weeks after chemotherapy	11,476.13±23,988.02	1,998.23±3,206.16	0.151
Initial CA 19-9/CA 19-9 at 12 weeks after chemotherapy	0.96±0.89	1.77±2.23	0.202

Values are presented as mean±SD or n (%).

PD, progressive disease; SD, stable disease; PR, partial response.

Table 3.

Factors Influencing Overall Survival More than One Year on Multivariate Logistic Regression Analysis

Variable	OR	p-value	95% CI
Age (≥65 yr vs. <65 yr)	2.615	0.295	0.432-15.824
Laboratory finding
BUN	0.833	0.039	0.701-0.990
CA 19-9 (>291 vs. ≤291)	0.637	0.635	0.099-4.094
Tumor size	2.190	0.049	1.005-4.773
Response after first 3 cycles
PD	6.271	0.228	0.175-25.060
SD	1.322	0.315	0.048-36.445
PR	1.000	0.869	-

PD, progressive disease; SD, stable disease; PR, partial response.

Table 4.

Factors Influencing Disease Progression Free Survival

Variable	Hazard ratio	p-value	95% CI
Univariate analysis
Age (≥65 yr vs. <65 yr)	1.202	0.578	0.629-2.298
Sex (male vs. female)	0.824	0.566	0.425-1.597
Laboratory finding
Hemoglobin	0.944	0.550	0.780-1.142
Albumin	1.074	0.783	0.646-1.786
INR	0.028	0.115	0.000-2.377
BUN	0.969	0.249	0.918-1.022
Creatinine	0.314	0.172	0.059-1.656
Total bilirubin	1.025	0.376	0.970-1.083
CEA (>8.56 vs. ≤8.56)	1.777	0.182	0.764-4.136
CA 19-9 (>291 vs. ≤291)	1.470	0.267	0.744-2.905
Tumor size	1.237	0.091	0.967-1.582
Tumor location (body or tail vs. head)	0.598	0.128	0.308-1.159
Carcinomatosis peritonei (yes vs. no)	2.468	0.096	0.852-7.148
Distant metastasis (yes vs. no)	2.529	0.010	1.253-5.103
Chemotherapy regimen (combination vs. mono)	0.633	0.168	0.330-1.213
Multivariate analysis
Age (≥65 yr vs. <65 yr)	1.506	0.278	0.718-3.168
Tumor size	1.437	0.211	0.867-7.682
Carcinomatosis peritonei (yes vs. no)	1.348	0.186	1.152-5.448
Distant metastasis (yes vs. no)	1.441	0.035	1.002-2.908

Table 5.

Factors Influencing Overall Survival

Variable	Hazard ratio	p-value	95% CI
Univariate analysis
Age (≥65 yr vs. <65 yr)	1.080	0.810	0.577-2.020
Sex (male vs. female)	0.769	0.400	0.417-1.418
Laboratory finding
Hemoglobin	0.911	0.315	0.76-1.092
Albumin	1.018	0.944	0.618-1.677
INR	0.615	0.811	0.011-3.147
BUN	0.963	0.159	0.915-1.015
Creatinine	0.298	0.145	0.058-1.518
Total bilirubin	1.033	0.219	0.981-1.087
CEA (>8.56 vs. ≤8.56)	1.723	0.209	0.737-4.024
CA 19-9 (>291 vs. ≤291)	1.807	0.070	0.953-3.425
Tumor size	1.513	0.001	1.179-1.943
Tumor location (body or tail vs. head)	0.730	0.315	0.394-1.350
Carcinomatosis peritonei (yes vs. no)	3.124	0.036	1.079-9.046
Distant metastasis (yes vs. no)	2.271	0.009	1.233-4.184
Chemotherapy regimen (combination vs. mono)	0.731	0.319	0.395-1.354
Response at 12 weeks after chemotherapy
PD	4.041	0.010	0.924-17.674
SD	1.564	0.064	0.363-6.743
PR	1.000	0.549	-
Initial CA 19-9/CA 19-9 at 12 weeks after chemotherapy	0.598	0.045	0.361-0.990
Multivariate analysis
Age (≥65 yr vs. <65 yr)	1.476	0.366	0.634-3.439
Tumor size	1.534	0.004	1.150-2.045
Carcinomatosis peritonei (yes vs. no)	2.194	0.330	0.452-10.659
Distant metastasis (yes vs. no)	2.143	0.065	0.953-4.819
Response at 12 weeks after chemotherapy
PD	3.788	0.208	0.428-33.532
SD	1.946	0.231	0.218-17.405
PR	1.000	0.551	-

PD, progressive disease; SD, stable disease; PR, partial response.

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