Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinoma

Vilalta-Lacarra, Anna; Aldaz, Azucena; Sala-Elarre, Pablo; Urrizola, Amaia; Chopitea, Á.; Arbea, Leire; Rotellar, Fernando; Pardo, Fernando; Martí‐Cruchaga, Pablo; Zozaya, Gabriel; Súbtil, José Carlos; Rodríguez-Rodríguez, Javier; Ponz-Sarvisé, Mariano

doi:10.1016/j.pan.2023.03.001

Cited by 2 publications

(1 citation statement)

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“…Noteworthy is the fact that due to its distinctive biodistribution [29], the dose intensity of oxaliplatin administered intravenously within the FFX protocol did not correlate with progression-free survival (PFS) in patients with resected PDAC. Therefore, a pharmacokinetically-guided dose adjustment of this drug to improve survival outcomes in these patients was not considered [30]. Our study involved the direct intratumoral injection and distribution of oxaliplatin, thus, surpassing the constraints imposed by its distinctive biodistribution.…”

Section: Discussionmentioning

confidence: 99%

Multisite Is Superior to Single-Site Intratumoral Chemotherapy to Retard the Outcomes of Pancreatic Ductal Adenocarcinoma in a Murine Model

Lazarovits,

Epelbaum,

Lachter

et al. 2023

Cancers

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Introduction: Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion. Aim: This study explores the efficacy of multisite intratumoral injections in improving a drug’s distribution while minimizing its side effects. Methods and Results: In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (p < 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (p < 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (p = 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (p = 0.007). Conclusions: Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC.

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Section: Discussionmentioning

confidence: 99%