Efficacy of Nab-Paclitaxel Plus Gemcitabine and Prognostic Value of Peripheral Neuropathy in Patients with Metastatic Pancreatic Cancer

You, Min Su; Ryu, Ji Kon; Choi, Yong‐Kook; Choi, Jung-Won; Huh, Gunn; Paik, Woo Hyun; Lee, Sang Hyub; Kim, Yong Tae

doi:10.5009/gnl18220

Cited by 8 publications

(5 citation statements)

References 30 publications

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“…Also considering the higher ORR and survival in our study, there may be room for modification in the chemotherapy regimen with further optimized and well-balanced oncologic benefits and adverse events. The prognostic role of treatment-related peripheral neuropathy was limited during nab-paclitaxel plus gemcitabine treatment for patients with metastatic pancreatic cancer (30), and the replace of gemcitabine with S-1 is expected to be associated with safer profiles. While generally manageable, various adverse events during treatment call for meticulous and specific monitoring.…”

Section: Discussionmentioning

confidence: 99%

S-1 Maintenance Therapy After First-Line Treatment With Nab-Paclitaxel Plus S-1 for Advanced Pancreatic Adenocarcinoma: A Real-World Study

et al. 2022

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BackgroundIn our previous phase II study, nab-paclitaxel plus S-1 (NPS) showed encouraging objective response rate (ORR) as first-line treatment for advanced pancreatic adenocarcinoma (APAC). This study aimed to evaluate the effectiveness and safety of S-1 maintenance after NPS in APAC and to explore factors predicting survival benefits when using S-1 maintenance.MethodsBetween 2014 and 2018 a total of 182 patients with APAC, who were primarily treated with NPS, were included. For patients without progression or with treatment discontinuation due to any reasons within 4 months during NPS treatment, S-1 monotherapy was administrable as maintenance therapy at the physicians’ discretion based on the patients’ preference and performance status. Efficacy and safety of S-1 maintenance were investigated.ResultsIn 123 patients without progression within 4 months during NPS treatment, 74 received S-1 maintenance and had median progression-free survival of 9.6 months and median overall survival of 16.7 months. Multivariable analysis showed that in patients receiving S-1 maintenance after first-line NPS therapy, an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, non-metastatic disease, and complete or partial response as best response to NPS chemotherapy were independently associated with better survival. The most common all-grade hematological and non-hematological adverse events were neutropenia (82.4%) and peripheral neurotoxicity (66.2%), respectively, and the most common ≥Grade 3 hematological and non-hematological adverse events were neutropenia (40.5%) and peripheral neurotoxicity (6.8%), respectively in patients who received S-1 maintenance.ConclusionsOur real-world study showed that S-1 maintenance after tumor response or stable disease induced by first-line NPS treatment was effective and well-tolerated for some patients with APAC, which offers a promising alternative treatment strategy with encouraging survival for APAC.

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Section: Discussionmentioning

confidence: 99%

S-1 Maintenance Therapy After First-Line Treatment With Nab-Paclitaxel Plus S-1 for Advanced Pancreatic Adenocarcinoma: A Real-World Study

et al. 2022

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“…In a Korean cohort study, Cho et al reported CIPN in more than 50% of patients, and 15 (18.5%) of these patients experienced severe grades of toxicity [ 8 ]. In the study by You et al, 13 (14.8%) patients developed grade 2 PN, while 16 (18.2%) developed grade 3 PN; 19.3% and 18.2% of all patients needed dose reduction and discontinuation of treatment due to PN, respectively [ 37 ]. In our study, 47 patients (30.7%) experienced grade 1–2 CIPN, and of these, 38 (80.8%) required dose reduction, and 30 (44.7%) discontinued treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Cho et al highlighted the presence of neurologic adverse events as independent survival prognostic factors (HR 0.302; 95% CI 0.130–0.702, p = 0.005) [ 8 ]. You et al reported a significantly longer survival rate in patients with CIPN compared to those without neuropathy in the naive model (10.13 vs. 15.53 months, p = 0.007), although this correlation was not confirmed in the landmark model at 6 months, used to reduce lead time bias (11.4 vs. 15.3 months) ( p = 0.089) [ 8 , 23 , 37 ]. Various studies of breast cancer have been conducted to identify clinical or molecular risk factors for the development of chemotherapy-induced neuropathy.…”

Section: Discussionmentioning

confidence: 99%

Association between Low-Grade Chemotherapy-Induced Peripheral Neuropathy (CINP) and Survival in Patients with Metastatic Adenocarcinoma of the Pancreas

Catalano

Aprile

Ramello

et al. 2021

JCM

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The combination of nab-paclitaxel and gemcitabine demonstrated greater efficacy than gemcitabine alone but resulted in higher rates of chemotherapy-induced peripheral neuropathy (CINP) in patients with metastatic pancreatic cancer (mPC). We aimed to evaluate the correlation between the development of treatment-related peripheral neuropathy and the efficacy of nab-P/Gem combination in these patients. mPC patients treated with nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 as a first-line therapy were included. Treatment-related adverse events, mainly peripheral neuropathy, were categorized using the National Cancer Institute Common Toxicity Criteria scale, version 4.02. Efficacy outcomes, including overall survival (OS), progression-free survival (PSF), and disease control rate (DCR), were estimated by the Kaplan–Meier model. A total of 153 patients were analyzed; of these, 47 patients (30.7%) developed grade 1–2 neuropathy. PFS was 7 months (95% CI (6–7 months)) for patients with grade 1–2 neuropathy and 6 months (95% CI (5–6 months)) for patients without peripheral neuropathy (p = 0.42). Median OS was 13 months (95% CI (10–18 months)) and 10 months (95% CI (8–13 months)) in patients with and without peripheral neuropathy, respectively (p = 0.04). DCR was achieved by 83% of patients with grade 1–2 neuropathy and by 58% of patients without neuropathy (p = 0.03). In the multivariate analysis, grade 1–2 neuropathy was independently associated with OS (HR 0.65; 95% CI, 0.45–0.98; p = 0.03). nab-P/Gem represents an optimal first-line treatment for mPC patients. Among possible treatment-related adverse events, peripheral neuropathy is the most frequent, with different grades and incidence. Our study suggests that patients experiencing CINP may have a more favorable outcome, with a higher disease control rate and prolonged median survival compared to those without neuropathy.

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“…Overall survival was longer in patients with CIPN than in patients without CIPN. In 2018, You et al 58) reported that OS was longer in metastatic PC patients with neuropathy ( n = 52, 15.53 months) than in metastatic PC patients without neuropathy ( n = 36, 10.13 months, p value = 0.007). In 2021, Catalano et al 59) reported that the median OS was 13 months and 10 months in metastatic PC patients with ( n = 47) and without grade 1-2 CIPN ( n = 106) ( p value = 0.04).…”

Section: Drug Treatmentmentioning

confidence: 99%

“…Patients with longer OS are administered more anticancer drugs; therefore, the OS of PC patients with CIPN might be longer than the OS of PC patients without CIPN. However, some PC patients with CIPN discontinued chemotherapy 58 , 60) . Therefore, CIPN should be treated by the treatment described above.…”

Section: Drug Treatmentmentioning

confidence: 99%

Drug treatment for chemotherapy-induced peripheral neuropathy in patients with pancreatic cancer

Sugimoto

Takagi

Suzuki

et al. 2022

FJMS

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Pancreatic cancer (PC) is a lethal disease where most tumors are too advanced at diagnosis for resection, leaving chemotherapy as the mainstay of treatment. Although the prognosis of unresectable PC is poor, it has been dramatically improved by new chemotherapy treatments, such as the combination of 5 -fluorouracil, oxaliplatin, irinotecan, and leucovorin (FOLFIRINOX) or gemcitabine plus nabpaclitaxel. However, as oxaliplatin and paclitaxel are common neurotoxic drugs, chemotherapyinduced peripheral neuropathy (CIPN) is a common and severe adverse effect of both treatments. As there are no agents recommended in the ASCO guidelines, we review the methods used to treat CIPN caused by PC treatment. The efficacy of duloxetine was observed in a large randomized controlled trial (RCT). In addition, pregabalin was more effective than duloxetine for CIPN in two RCTs. Although duloxetine and pregabalin can be effective for CIPN, they have several side effects. Therefore, the choice between the two drugs should be determined according to effect and tolerability. Mirogabalin is also used in patients with PC and there is hope it will yield positive outcomes when treating CIPN in the future.

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Efficacy of Nab-Paclitaxel Plus Gemcitabine and Prognostic Value of Peripheral Neuropathy in Patients with Metastatic Pancreatic Cancer

Cited by 8 publications

References 30 publications

S-1 Maintenance Therapy After First-Line Treatment With Nab-Paclitaxel Plus S-1 for Advanced Pancreatic Adenocarcinoma: A Real-World Study

S-1 Maintenance Therapy After First-Line Treatment With Nab-Paclitaxel Plus S-1 for Advanced Pancreatic Adenocarcinoma: A Real-World Study

Association between Low-Grade Chemotherapy-Induced Peripheral Neuropathy (CINP) and Survival in Patients with Metastatic Adenocarcinoma of the Pancreas

Drug treatment for chemotherapy-induced peripheral neuropathy in patients with pancreatic cancer

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