Clinical significance of serum alkaline phosphatase level in advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 183-183 ◽  
Author(s):  
I. Ohno ◽  
S. Mitsunaga ◽  
K. Nakachi ◽  
S. Shimizu ◽  
H. Takahashi ◽  
...  

183 Background: Alkaline phosphatase (ALP) is an enzyme that is elevated by various hepatobiliary diseases. Generally its elevation is thought to indicate bile stasis. There are some reports that show ALP is an important prognostic factor for several cancers such as colon, lung, and gastric cancer. Often it is speculated that ALP elevation indicates bile stasis caused by liver metastasis. However, the significance of ALP elevation in advanced pancreatic cancer (APC) patients is not well evaluated. The aim of this study was to determine the significance of elevated serum ALP as a prognostic factor in patients with APC even without jaundice and liver metastasis. Methods: Serum ALP levels were measured in 393 patients with APC receiving gemcitabine monotherapy before treatment, and according to those levels, patients were subgrouped (ALP<upper normal limit (UNL), UNL-500 U/L, 501-700 U/L, 701-1000 U/L, 1000U/L < ALP). The clinical data of each group were analyzed to see characteristics of elevated ALP patients. The relationship between ALP level and survival, response were also examined. Results: The elevated ALP group included poor performance status (PS>1) patients (41.3%, p=0.001), and associated with low serum albumin (3.31±0.38, p<0.01). The elevated ALP group (median survival time (MST) 112 days) showed significantly worse prognosis and lower disease control rate compared to the normal ALP group (MST 217days) (p<0.001, p<0.001). Multivariate analysis revealed ALP (p<0.001), CRP (p<0.001), ascites (p<0.001), distant metastasis (p=0.003), white blood cell count (p=0.005), PS (p=0.020), AST (p=0.020), and ALT (p=0.020) were independent prognostic factors. Similar results were seen in liver metastasis free patients without jaundice. Conclusions: Elevated serum ALP level correlated with poor performance status and low serum albumin. ALP was also the independent prognostic factor in liver metastasis free APC patients without jaundice. No significant financial relationships to disclose.

2020 ◽  
Vol 13 ◽  
pp. 175628482097491
Author(s):  
Hasan Rehman ◽  
Jeffrey Chi ◽  
Nausheen Hakim ◽  
Shreya Prasad Goyal ◽  
Coral Olazagasti ◽  
...  

Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in patients with advanced pancreatic cancer (APC). However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients >65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged >65 years with chemo-naïve APC with Eastern Cooperative Oncology Group performance status ⩽2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using the Kaplan–Meier method. Adverse events were recorded on the day of chemotherapy. Cancer antigen 19.9 was measured in every cycle and restaging scans were performed every two cycles. Results: A total of 73 patients (median age: 73 years; range: 66–93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months, respectively. Around 66% of patients received growth-factor support based on American Society of Clinical Oncology guidelines and no patient developed neutropenic fever. The incidences of grade ⩾3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5%, respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients, respectively. Conclusion: In patients older than >65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with the historical control from the MPACT study. This regimen allowed for fewer dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as a favorable side-effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with poor performance status, such as those with pancreatic cancer, and in order to combine with a third agent, such as a targeted treatment or immunotherapy.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 405-405
Author(s):  
Se Jun Park ◽  
Myung Ah Lee

405 Background: There is few data for effective second-line treatment in advanced pancreatic cancer, and most patients have poor performance status after progressive disease. We evaluated the efficacy, toxicity, and median dose intensity of oral chemotherapy, capecitabine, or TS-1 in gemcitabine-refractory advanced pancreatic cancer for second-line treatment. Methods: Patients who have progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between Jan. 2011 and Nov. 2017. These patients were treated with capecitabine or TS-1 as second-line treatment. Capecitabine were administered as 2,500 mg/m2 divided dose on day 1-14, followed by one week rest. In TS-1 group, TS-1 was taken orally based on patient’s BSA (60mg twice daily in BSA > 1.5, 50mg twice daily in BSA 1.25-1.5, and 40mg twice daily in BSA < 1.25) through 28 days, by two week rest. Median dose intensity was compared by calculating a percent of target dose achieved in the average cycle for each patient. Results: Of the total 62 patients, 41 patients were treated with capecitabine and 21 patients were treated with TS-1. The median age was 61 years for the capecitabine group compared with 62 years for the TS-1 group. In capecitabine group, males were 56%, and in TS-1 group, males were 66%. 29% of capecitabine group received prior fluorouracil base therapy, and 47% of TS-1 group were receiving such therapy. The objective response rate was similar in the two groups: 12.2% with capecitabine and 4.8% with TS-1 (p = 0.358). There was no difference in median progression free survival between capecitabine and TS-1 (2.1 months vs. 2.7 months, p = 0.102), however, TS-1 group showed better median overall survival time than capecitabine group (6.9 months vs. 4.6 months, p = 0.048). Most of the adverse events were similar in both group, except that grade 3 or 4 mucositis was more common in TS-1 group. There was no significant difference in median dose intensity between two groups. (Capecitabine 91.5% vs. TS-1 90.1%, p = 0.216). Conclusions: Oral agents such as TS-1 or capecitabine can be second-line treatment for advanced pancreatic cancer patients with poor performance status after progression to gemcitabine-based regimen.


2017 ◽  
Vol 13 (3) ◽  
pp. 157-166 ◽  
Author(s):  
Lauren M. Rosati ◽  
Joseph M. Herman

Literature on the management of nonmetastatic pancreatic ductal adenocarcinoma in patients who are elderly or have poor performance status is sparse. The median survival of this unique cohort of patients is < 6 months, and most patients are only offered single-agent gemcitabine or supportive care. Recently, adding nanoparticle albumin-bound paclitaxel to gemcitabine was shown to improve survival of patients with metastatic disease with Eastern Cooperative Group performance status of 2. Although standard chemoradiotherapy provides long-term locoregional control in locally advanced pancreatic cancer, it is difficult for this group of patients to tolerate 6 weeks of therapy. Stereotactic body radiotherapy (SBRT) can be delivered in only 3 to 5 days, does not require concurrent chemotherapy, and has limited toxicity, and tumor control rates appear to be equivalent to or better than those achieved with standard chemoradiotherapy. Additionally, SBRT has been shown to improve cancer-related pain and patient-reported quality of life. Given the favorable toxicity profile, SBRT seems like an obvious choice for patients who are elderly, have multiple comorbidities, or have poor performance status. Herein, we review the literature on SBRT in this unique patient population and discuss future directions.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 361-361
Author(s):  
Gillian Gresham ◽  
Sylvia Ng ◽  
Anderson Chang ◽  
Shannon Valdez ◽  
Sharlene Gill

361 Background: Surgical resection offers the only hope for long-term disease control in patients (pts) with pancreatic adenocarcinoma. Randomized trials (ESPAC 1, ESPAC3) further support a role for adjuvant chemotherapy (AC) in the management of pancreatic cancer (PC). Trial outcomes may not reflect clinical reality due to pt selection bias, and it is often difficult to predict which pts are most likely to benefit from adjuvant intervention. Methods: Consecutive pts between 2003 and 2008 referred to the BC Cancer Agency (BCCA) with operative intent at diagnosis (dx) were retrospectively reviewed. Results: 145 pts were identified; median age 65 years (y) (range 38-84), male/female (45.5%, 54.5%). EUS/PET staging was performed in 21% of pts. Median CA19-9 value at dx was 210 ku/L. Pancreaticoduodenectomy was performed in 65% of pts. Complete resection (RO) of tumours occurred in 87 pts (60%) overall. 66% of pts were node positive. 43% of pts were subsequently treated with adjuvant therapy (AT) where 5% of these pts received chemoradiotherapy and 95% received AC (65% gemcitabine). There was no statistically significant difference in either OS (p=0.39) or DFS (p=0.28) amongst resected pts who were treated by sx alone versus pts who received AC. In subgroup analysis, AC was associated with significantly improved OS in pts (n=58) with positive margins (R1) (median 17.3 mos vs 8.9 mos, p=0.0045) but benefit was not seen in R0 pts (n=87) (22.9 mos vs 22.4 mos, p=0.20). In multivariate analysis, poor performance status (ECOG 3-4), weight loss of more than 10% of initial body weight, baseline CA19-9 value greater than 210 ku/L, positive nodes, R1 status and histological grade 3-4 were significant adverse prognostic factors. Conclusions: PC continues to have poor outcomes with a 5yOS of 5% in pts treated with sx alone. Among pts with resectable PC treated at the BCCA, AC tended towards increased DFS and OS. Although R1 status was associated with inferior OS, the benefit of AT was greater in this subgroup. [Table: see text]


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 391-391
Author(s):  
Toshihiko Matsumoto ◽  
Ukyo Okazaki ◽  
Yusuke Kurioka ◽  
Shogo Kimura ◽  
Takao Tsuzuki ◽  
...  

391 Background: Nivolumab has changed the treatment of advanced gastric cancer (AGC). Nivolumab shows better outcome compared to best supportive care in AGC patients who received at least two prior regimen. Although there is not reliable date of poor performance status(PS) AGC patients who received nivolumab. We investigated efficacy and safety of nivolumab for AGC patients with poor PS. Methods: We retrospectively collected clinicopathologic data from patients with AGC who received nivolumab monotherapy in Himeji Red Cross Hospital from October 2017 to June 2019. Results: 49 AGC patients who received nivolumab were analyzed. 27 patients were PS 0 or 1(Good Group), and 22 patients were PS 2 or 3(Poor Group). Median progression free survival and overall survival was 61 days and 180 days in Good Group and 36 days and 85 days in Poor Group. Overall survival (OS) was significantly shorter in Poor group(180 days vs 85 days, p = 0.0255). Disease control rate was 23% in Good group and 9% in Poor group. 33% patients were experienced immune related adverse event (iRAE) in Good Group, and 18% in Poor Group. We investigated prognostic factor of OS in Poor Group such as Royal Marsden Hospital Score(RMH score), modified Glasgow prognostic score(mGPS), and Japan Clinical Oncology Group (JCOG) prognostic index. RMH score and JCOG prognostic index good or moderate group was significantly longer overall survival than poor group (93 days vs 35 days (p = 0.0214)). JCOG prognostic index was most correlated with OS among these tools. Conclusions: This study suggested that nivolumab has a modest effect and is feasible as third line or later line for AGC patients. JCOG prognostic index was suggested to be effective in predicting prognosis in AGC patients who received nivolumab.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 705-705
Author(s):  
Hasan Rehman ◽  
Jeffrey Chi ◽  
Nausheen Hakim ◽  
Shreya Prasad Goyal ◽  
Coral Olazagasti ◽  
...  

705 Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in APC. However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients > 65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged > 65 years with chemo-naive APC and ECOG PS < 2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using Kaplan-Meier method. Adverse events were recorded on the day of chemotherapy. CA19-9 was measured every cycle and restaging scans were performed every two cycles. Results: Seventy-three patients (median age: 73; range: 66 - 93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months respectively. 66% of patients received growth factor support based on ASCO guidelines and no patients developed neutropenic fever. The incidence of grade > 3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5% respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients respectively. Conclusions: In patients > 65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with historical control from the MPACT study. This regimen allowed for less dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as favorable side effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with APC and poor performance status. Better tolerability may allow for combination with a third agent, such as a targeted or immunotherapy.


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4842
Author(s):  
Hidetaka Suzuki ◽  
Shuichi Mitsunaga ◽  
Masafumi Ikeda ◽  
Takao Aoyama ◽  
Kazumi Yoshizawa ◽  
...  

We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment. Serum GDF-15 levels and multiple protein expressions in lysates extracted from liver metastasis were measured by enzyme-linked immuno-sorbent assay and reverse-phase protein array, respectively. The cut-off for serum GDF-15 was determined as 3356.6 pg/mL, the mean plus two standard deviations for benign pancreatic disease. The high-GDF-15 group was characterized as showing low Karnofsky performance status (KPS) (p = 0.037), poor Eastern Cooperative Oncology Group performance status (ECOG-PS) (p = 0.049), severe appetite loss (p = 0.011), and high serum levels of carbohydrate antigen 19-9 (p = 0.019) and C-reactive protein (p = 0.009). Tumors of the high-GDF-15 group expressed high levels of phosphorylated (p)JNK (p = 0.007) and pAkt (p = 0.040). APC patients with high serum GDF-15 showed signatures of cachexia and activation of the signaling pathways involving Akt and JNK in the tumor. This study indicated circulating GDF-15 could be associated with cachectic symptoms in APC.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5000-5000
Author(s):  
Vangelis Eleftherakis-Papaiakovou ◽  
Athanasios Anagnostopoulos ◽  
Aristotelis Bamias ◽  
Dimitra Gika ◽  
Argiris Symeonidis ◽  
...  

Abstract Introduction: Renal failure (RF) is a common and severe complication of patients with multiple myeloma (MM). The purpose of our study was to assess the incidence of RF in a contemporary series of newly diagnosed patients with MM, its association with specific clinical and laboratory features and its impact on early death rate, on myeloma response and on patients survival. Patients and Methods: Between January 1995 and December 2004, 756 newly diagnosed symptomatic patients with MM were included in the database of the GMSG. Renal failure, was defined as a serum creatinine ≥2mg/dL at the time of diagnosis. The incidence of RF was correlated with multiple clinical and laboratory variables by univariate and Cox regression analysis. Results: The incidence of RF in this series of patients was 21%. This figure was similar to the incidence of RF (19%) in patients diagnosed during the preceding decade. Severe RF (serum creatinine ≥6mg/dL) occurred in 4% of patients. There was a significant association of renal failure with poor performance status (p=0.001), increased ISS stage (p&lt;0.001), elevated serum β2microglobulin (p&lt;0.001), hypercalcemia (p&lt;0.001), increased Bence Jones proteinuria (p&lt;0.001), high serum LDH (p&lt;0.002), low platelet count (p=0.004), low albumin (p=0.036) and light chain only on IgD myeloma (p&lt;0.001). Multivariate analysis showed that RF was independently associated only with ISS and Bence Jones proteinuria. Early death, within 2 months from treatment initiation, was observed in 10% of patients with RF and in 4% of patients without RF (p=0.2). At least partial response (EBMT criteria) was documented in 61% of patients without RF and in 55% of patients with RF (p=0.2). The median survival of patients with RF was 19.5 months versus 40.4 months for patients without RF (p&lt;0.001). Other variables associated with impaired survival by univariate analysis included poor performance status, thrombocytopenia, hypercalcemia, high serum LDH, advanced age and elevated serum β2 microglobulin. However, when multivariate analysis was performed the independent variables were poor performance status, thrombocytopenia, advanced age, high LDH and elevated serum β2 microglobulin but not high creatinine. The median survival of patients with ISS stage 2 and 3 without RF was 36 months and 22 months respectively compared to 19 months and 20 months for patients with RF (p=0.1 and 0.5 respectively). Conclusions: The incidence of RF remains significant and essentially unchanged in patients with MM diagnosed over the last 20 years. The presence of RF is associated with a trend for higher early death rate but with a similar response to primary therapy. Patients with RF have lower survival compared to patients without RF. The prognostic significance of RF is mainly attributed to its association with higher β2;microglobulin and Bence Jones proteinuria.


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