Comparison between FOLFIRINOX and gemcitabine plus nab-paclitaxel including sequential treatment for metastatic pancreatic cancer: a propensity score matching approach

Abstract

Background FOLFIRINOX (FFX) and Gemcitabine plus nab-paclitaxel (GnP) have been recommended as the first-line chemotherapy for metastatic pancreatic cancer (mPC). However, the evidence is lacking comparing not only two regimens, but also sequential treatment (FFX–GnP vs. GnP–FFX). Methods Data of 528 patients (FFX, n = 371; GnP, n = 157) with mPC were collected retrospectively. Propensity score matching was conducted to alleviate imbalance of the two groups. Overall survival (OS), progression free survival (PFS), and toxicity of patients were analyzed. Results In the whole population, OS (12.5 months vs. 10.3 months, P = 0.05) and PFS (7.1 months vs. 5.8 months, P = 0.02) were longer in the FFX group before matching and after matching (OS: 11.8 months vs. 10.3 months, P = 0.02; PFS: 7.2 months vs. 5.8 months, P < 0.01). For sequential treatment, OS and PFS showed no significant difference. Interruptions of chemotherapy due to toxicities were more frequent (6.8 vs. 29.3%, P < 0.001) in the GnP group, and cessation of chemotherapy showed a significant association with mortality (z = − 1.94, P = 0.03). Conclusions FFX achieved a longer overall survival than GnP in mPC, but not in the comparison for sequential treatment. More frequent adverse events followed by treatment interruptions during GnP might lead to a poor survival outcome. Therefore, FFX would be a better first-line treatment option than GnP for mPC.

HNRNPC regulates RhoA to induce DNA damage repair and cancer‐associated fibroblast activation causing radiation resistance in pancreatic cancer

“…7,8 Current first-line chemotherapeutic regimens for metastatic pancreatic cancer patients involve treatment with either FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin) or gemcitabine plus nab-paclitaxel, 9 with recent studies indicating that FOLFIRINOX may be the better option. 10 However, the eventual and inevitable development of chemo-and radioresistance significantly limits their treatment efficacy. 9,11 PC cells are particularly prone to developing endogenous and exogenous resistance to gemcitabine.…”

“…Although surgical resection and adjuvant therapy are common treatment strategies for PC depending on the stage of disease, 6 recent studies have demonstrated the benefits of applying a neoadjuvant approach, which include controlling potential micrometastases (usually present at the time of diagnosis), and determining which patients would benefit from surgery while sparing unsuitable patients from major surgical intervention 7,8 . Current first‐line chemotherapeutic regimens for metastatic pancreatic cancer patients involve treatment with either FOLFIRINOX (folinic acid, 5‐fluorouracil, irinotecan and oxaliplatin) or gemcitabine plus nab‐paclitaxel, 9 with recent studies indicating that FOLFIRINOX may be the better option 10 . However, the eventual and inevitable development of chemo‐ and radioresistance significantly limits their treatment efficacy 9,11 .…”

Impact of Baseline Muscle Mass and Myosteatosis on the Development of Early Toxicity During First-Line Chemotherapy in Patients With Initially Metastatic Pancreatic Cancer

“…However, both regimens carry unfavorable toxicity profiles ( 4 ) which could ultimately result in treatment interruption, and a considerable portion of patients require dose modification, treatment delay or cessation in both regimens due to toxicity ( 5 ). As the treatment-related adverse events lead to deterioration of patients’ quality of life and treatment interruption leading to unfavorable prognosis and poor survival ( 6 – 9 ), it would be important to predict those who are likely to experience chemotherapy-associated toxicity.…”

“…Several studies have shown the impact of sarcopenia and myosteatosis on the outcome of PDAC patients ( 21 – 23 ) but most were based on resectable PDAC and assessed their impact on postoperative mortality. The data on patients with advanced or metastatic PDAC undergoing palliative treatment is scarce ( 9 , 24 , 25 ) and have mainly focused on patient’s survival rather than treatment-related toxicity. Choi et al.…”

“…Kim et al. ( 9 ) and Rollins et al. ( 25 ) have evaluated the impact of skeletal muscle index (SMI) and density (SMD) on the prognosis of metastatic PDAC, however the results were conflicting.…”