Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged 65 years or older with advanced pancreatic cancer

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.

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Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged > 65 years with advanced pancreatic cancer (APC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.705 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 705-705

Author(s):

Hasan Rehman ◽

Jeffrey Chi ◽

Nausheen Hakim ◽

Shreya Prasad Goyal ◽

Coral Olazagasti ◽

...

Keyword(s):

Performance Status ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Poor Performance ◽

Poor Performance Status ◽

Weekly Schedule ◽

Free Survival ◽

Kaplan Meier ◽

Ecog Ps ◽

Dose Reductions

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.

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Trabectedin in Advanced Sarcomas—Experience at a Tertiary Care Center and Review of Literature

South Asian Journal of Cancer ◽

10.1055/s-0041-1734336 ◽

2021 ◽

Vol 10 (02) ◽

pp. 53-57

Author(s):

Saurav Verma ◽

Kaushal Kalra ◽

Sameer Rastogi ◽

Ekta Dhamija ◽

Avinash Upadhyay ◽

...

Keyword(s):

Group Performance ◽

Care Center ◽

Performance Status ◽

Tertiary Care ◽

Eastern Cooperative Oncology Group ◽

Soft Tissue Sarcomas ◽

Progression Free Survival ◽

Poor Performance ◽

Median Number ◽

Poor Performance Status

Abstract Background There is sparse literature on trabectedin in advanced soft-tissue sarcomas from developing world. It would be interesting to know about use and outcomes of trabectedin in Indian patients. Method In a retrospective study, consecutive patients treated with trabectedin from 2016 to 2019 were analyzed. Patients with L-sarcomas were treated at a dose of 1.5 mg/m2, while those with translocation-related sarcomas were treated at a dose of 1.2 mg/m2 as a 24-hour infusion through peripherally inserted central catheter line. From July 2019, infusions were administered through an ambulatory elastomeric pump, while before that patients were admitted for 24 hours. We used SPSS version 23.0 for statistical calculation. Result A total of 20 patients received trabectedin with a total of 116 infusions. The median age was 46 years (range: 22–73 years). The male (n = 11, 55%) and female patients were almost equal (n = 9, 45%). Thirteen patients (65%) had Eastern Cooperative Oncology Group Performance Status 1. Majority of the patients had leiomyosarcoma (n = 8, 40%); remaining comprised of liposarcoma (3, 15%), translocation-related sarcomas excluding myxoid liposarcoma (n = 8, 40%) and others (n = 1,5%). Most common site was extremity (n = 11, 55%) followed by retroperitoneal (n = 3, 15%), visceral (n = 3, 15%), and others (n = 3,15%). Median number of previous lines received was 2 (range: 0–4). Median number of trabectedin cycles received was 4 (range: 1–17). Best response assessed was stable disease (n = 10, 50%), progressive disease (n = 6, 30%), partial response (n = 1, 5%), and not assessed in 3 patients. After a median follow-up of 19 months, median progression-free survival was 4 months. Conclusion In this heavily treated population (composed of L-sarcomas and translocation-related sarcomas) with many patients with poor performance status, the outcome with trabectedin is in synchrony with literature. However, the need of 24-hour admission might deter quality of life. Elastomeric pump seems to be a reasonable alternative to admission and can be a breakthrough in administering trabectedin, especially in developing countries.

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Role of Stereotactic Body Radiotherapy in the Treatment of Elderly and Poor Performance Status Patients With Pancreatic Cancer

Journal of Oncology Practice ◽

10.1200/jop.2016.020628 ◽

2017 ◽

Vol 13 (3) ◽

pp. 157-166 ◽

Cited By ~ 11

Author(s):

Lauren M. Rosati ◽

Joseph M. Herman

Keyword(s):

Pancreatic Cancer ◽

Stereotactic Body Radiotherapy ◽

Group Performance ◽

Performance Status ◽

Single Agent ◽

Locally Advanced ◽

Poor Performance ◽

Tumor Control ◽

Poor Performance Status ◽

Patient Reported

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.183 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 183-183 ◽

Cited By ~ 1

Author(s):

I. Ohno ◽

S. Mitsunaga ◽

K. Nakachi ◽

S. Shimizu ◽

H. Takahashi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Liver Metastasis ◽

Prognostic Factor ◽

Performance Status ◽

Elevated Serum ◽

Advanced Pancreatic Cancer ◽

Poor Performance ◽

Poor Performance Status ◽

Bile Stasis ◽

Low Serum

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.

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LAPACT: An open-label, multicenter phase II trial of nab-paclitaxel (nab-P) plus gemcitabine (Gem) in patients (pts) with locally advanced pancreatic cancer (LAPC).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.tps477 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. TPS477-TPS477 ◽

Cited By ~ 3

Author(s):

Philip Agop Philip ◽

Jill Lacy ◽

Scot D. Dowden ◽

Javier Sastre ◽

Venu Gopal Bathini ◽

...

Keyword(s):

Group Performance ◽

Performance Status ◽

Locally Advanced ◽

Eastern Cooperative Oncology Group ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

The United States ◽

Phase Iii ◽

Open Label ◽

Primary Tumors

TPS477 Background: In pts with LAPC, more effective systemic therapies may be associated with improved local control, delay of metastasis, and overall survival (OS). The phase III MPACT trial in pts with metastatic PC demonstrated longer OS (median, 8.7 vs 6.6 mos; HR, 0.72; P < 0.001) and an ≈ 3-fold greater shrinkage of primary tumors with nab-P + Gem vs Gem alone (−22.15% vs −7.02%), raising the possibility of improved local PC control with nab-P + Gem. LAPACT will assess the efficacy and safety of nab-P + Gem in LAPC. Methods: LAPACT will enroll treatment-naive pts (planned n ≈ 110) in the United States, Canada, and Europe with Eastern Cooperative Oncology Group performance status ≤ 1, confirmed unresectable LAPC, no distant metastases, and adequate organ function. Pts with mixed-origin tumors, any other malignancy within 5 years, peripheral neuropathy grade > 1, or clinically significant ascites are ineligible. Pts will receive nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle. Pts without progressive disease (PD) or unacceptable toxicity after 6 cycles will receive investigator’s choice of surgery, chemoradiotherapy, or continued nab-P + Gem. If a major response is observed, surgery may occur prior to completing 6 cycles of nab-P + Gem. The primary endpoint is time to treatment failure (TTF; time from first therapy dose to discontinuation due to PD, start of a new non–protocol-defined anti-cancer therapy, or death). The study design allows for 80% power at a 1-sided α of 0.05 to detect a 30% increase over the 5.1-month median TTF observed for nab-P + Gem in the MPACT study. The secondary endpoints are disease control rate (DCR) after 6 cycles, overall response rate, progression-free survival, OS, safety, and quality of life. The exploratory endpoint is correlation of changes in circulating nucleic acids with PD and treatment response. An interim DCR analysis will occur after all pts have completed 6 cycles of nab-P + Gem, discontinued therapy due to PD, died, or started a new non–protocol-defined therapy before completing 6 cycles of therapy. Enrollment is ongoing (first pt enrolled in April 2015). Clinical trial information: NCT02301143.

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Oral chemotherapy as second-line treatment option for gemcitabine-refractory advanced pancreatic cancer with poor performance status.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.405 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 405-405

Author(s):

Se Jun Park ◽

Myung Ah Lee

Keyword(s):

Pancreatic Cancer ◽

Performance Status ◽

Advanced Pancreatic Cancer ◽

Dose Intensity ◽

Poor Performance ◽

Poor Performance Status ◽

Line Treatment ◽

Second Line ◽

Median Dose ◽

Gemcitabine Refractory

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.

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Digital Detection of Sarcopenia in Pancreatic Cancer: Additional Utilization to Plan Patient Management

10.21203/rs.3.rs-657909/v1 ◽

2021 ◽

Author(s):

Mustafa Jalal ◽

Jennifer A Campbell ◽

Jonathan Wadsley ◽

Andrew D Hopper

Keyword(s):

Skeletal Muscle ◽

Pancreatic Cancer ◽

Group Performance ◽

Performance Status ◽

Locally Advanced ◽

Eastern Cooperative Oncology Group ◽

Advanced Pancreatic Cancer ◽

Skeletal Muscle Index ◽

Ecog Ps ◽

Cancer Network

Abstract Purpose: The presence of a sarcopenia adversely affects the prognosis of patients with pancreatic cancer. There is an emerging role for using computed tomography (CT) to calculate skeletal muscle index (SMI) and the presence of sarcopenia. The aim of this study was to assess if detecting ‘digital sarcopenia’ is feasible and can contribute to the management of patients with locally advanced pancreatic cancer (LAPC).Methods: Patients diagnosed with LAPC referred for endoscopic ultrasound guided biopsy (EUS-B) by our regional cancer network were identified. Age, body mass index (BMI), and Eastern Cooperative Oncology Group performance status (ECOG-PS) was noted. CT images were analysed for SMI and the presence of sarcopenia. Decision outcomes on receiving chemotherapy or not were collected from the regional oncology database. Results: In total 51/204 (25%) patients with LAPC who underwent EUS-B were not given chemotherapy and received BSC only. The prevalence of sarcopenia (p=0.0003), age ≥ 75 years old (p=0.03) and ECOG-PS 2-3 (p=0.01) were significantly higher in the patents receiving BSC only. Logistic regression analysis demonstrated that SMI was the only independent associated factor identifying patients with LAPC who were treated with BSC only and not chemotherapy after adjusting for age and ECOG-PS. Conclusion: Our study has shown that digital skeletal muscle analysis at the time of a diagnostic CT for patients with pancreatic cancer is feasible and can detect sarcopenia and malnourished patients who are much less likely to take up chemotherapy. These patients could be triaged to oncology assessment prior to EUS-B to avoid unnecessary investigations.

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Computed Tomographic Sarcopenia in Pancreatic Cancer: Further Utilization to Plan Patient Management

Journal of Gastrointestinal Cancer ◽

10.1007/s12029-021-00672-4 ◽

2021 ◽

Author(s):

Mustafa Jalal ◽

Jennifer A. Campbell ◽

Jonathan Wadsley ◽

Andrew D. Hopper

Keyword(s):

Skeletal Muscle ◽

Pancreatic Cancer ◽

Group Performance ◽

Performance Status ◽

Locally Advanced ◽

Eastern Cooperative Oncology Group ◽

Advanced Pancreatic Cancer ◽

Skeletal Muscle Index ◽

Computed Tomographic ◽

Ecog Ps

Abstract Purpose The presence of a sarcopenia adversely affects the prognosis of patients with pancreatic cancer. There is an emerging role for using computed tomography (CT) to calculate skeletal muscle index (SMI) and the presence of sarcopenia. The aim of this study was to assess if detecting ‘computed tomographic sarcopenia’ is feasible and can contribute to the management of patients with locally advanced pancreatic cancer (LAPC). Methods Patients diagnosed with LAPC referred for endoscopic ultrasound-guided biopsy (EUS-B) by our regional cancer network were identified. Age, body mass index (BMI), and Eastern Cooperative Oncology Group performance status (ECOG-PS) were noted. CT images were analysed for SMI and the presence of sarcopenia. Decision outcomes on receiving chemotherapy or not were collected from the regional oncology database. Results In total, 51/204 (25%) patients with LAPC who underwent EUS-B were not given chemotherapy and received best supportive care (BSC) only. The prevalence of sarcopenia (p = 0.0003), age ≥ 75 years old (p = 0.03), and ECOG-PS 2–3 (p = 0.01) were significantly higher in the patients receiving BSC only. Logistic regression analysis demonstrated that SMI was the only independent associated factor identifying patients with LAPC who were treated with BSC only and not chemotherapy after adjusting for age and ECOG-PS. Conclusion Our study has shown that computed tomographic skeletal muscle analysis at the time of a diagnostic CT for patients with pancreatic cancer is feasible and can detect sarcopenia and malnourished patients who are much less likely to take up chemotherapy. These patients could be triaged to oncology assessment prior to EUS-B to avoid unnecessary investigations.

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