Influcence of Localization of Primary Tumor on Effectiveness of 5-Fluorouracil/Leucovorin Combined with Irinotecan and Oxaliplatin (FOLFIRINOX) in Patients with Metastatic Pancreatic Adenocarcinoma: A Retrospective Study
PhD. Georges-Francois Leclerc Cancer Center, 1 rue du professeur Marion, Dijon 21000, France. . Anticancer research
(Impact Factor: 1.83).
Metastatic pancreatic carcinoma is an incurable disease and gemcitabine remains the standard of care in first-line chemotherapy. Recently, fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) demonstrated their superiority in first-line therapy. The objective of this study was to determine the efficacy of FOLFIRINOX in either first- and second-line treatment and to compare its efficacy in regard to the location of the primary tumor.
We performed a retrospective analysis of clinical factors associated with patients' survival using a cohort of 42 patients treated by FOLFIRINOX in either first- or second-line (2006-2011) and a control cohort of 42 patients matched on sex and age without FOLFIRINOX treatment was obtained from a previous period of time (2001-2005).
The median follow-up was 10 months. The median overall survival was 10 months for the whole cohort and 10 and 12 months for patients treated at first- and second-line, respectively (p<0.05). In this cohort using a multivariate model, among classical prognosis factors, only primary location in the head was associated with poor outcome. The median overall survival was 8 months for patients with primary location in the head and 14 months for patients with primary location in the corpse or tail (p=0.02). In the gemcitabine cohort, the median follow-up was 8 months. Using a multivariate model, only performance status was associated with outcome. The median overall survival was 9 versus 6.5 months for patients with tumor, of the head versus tail or corpse tumor respectively (p<0.05).
This retrospective study suggests the same efficacy of FOLFIRINOX used either in first- or second- line therapy for pancreatic cancer. Importantly, FOLFIRINOX compared favorably to gemcitabine only for patients with tumor of the corpse or tail. Further prospective trials are warranted to evaluate the efficacy of FOLFIRINOX in patients with tumor of the head of the pancreas.
Available from: Eui-Joon Kil
- "Oxaliplatin, a third-generation diaminocyclohexane (DACH) platinum drug, is widely used alone or in combination with fluorouracil and leucovorin to treat metastatic colorectal, ovarian, and pancreatic cancers123. However, oxaliplatin is associated with common and severe side effects. "
[Show abstract] [Hide abstract]
ABSTRACT: Oxaliplatin is a platinum-based anticancer drug used to treat metastatic colorectal, breast, and lung cancers. While oxaliplatin kills cancer cells effectively, it exhibits several side effects of varying severity. Neuropathic pain is commonly experienced during treatment with oxaliplatin. Patients describe symptoms of paresthesias or dysesthesias that are triggered by cold (acute neuropathy), or as abnormal sensory or motor function (chronic neuropathy). In particular, we found that aluminum levels were relatively high in some cancer patients suffering from neuropathic pain based on clinical observations. Based on these findings, we hypothesized that aluminum accumulation in the dorsal root ganglion (DRG) in the course of oxaliplatin treatment exacerbates neuropathic pain. In mice injected with oxaliplatin (three cycles of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest), we detected cold allodynia using the acetone test, but not heat hyperalgesia using a hot plate. However, co-treatment with aluminum chloride (AlCl3∙6H2O; 7 mg/kg i.p. for 14 days: equivalent 0.78 mg/kg of elemental Al) and oxaliplatin (1 cycle of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest) synergistically induced cold allodynia as well as increased TRPAl mRNA and protein expression. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis showed a significant increase in aluminum concentrations in the DRG of mice treated with aluminum chloride and oxaliplatin compared to aluminum chloride alone. Similarly, in a mouse induced-tumor model, aluminum concentrations were increased in DRG tissue and tumor cells after oxaliplatin treatment. Taken together, these findings suggest that aluminum accumulation in the DRG may exacerbate neuropathic pain in oxaliplatin-treated mice.
Available from: Michael J Tapner
[Show abstract] [Hide abstract]
ABSTRACT: Background: This prospective, open-label phase II study assessed the impact of liver-directed therapy with selective internal radiation therapy (SIRT) and systemic chemotherapy on progression-free survival (PFS) in liver-dominant metastatic pancreatic adenocarcinoma.
[Show abstract] [Hide abstract]
ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) can be divided into head, body and tail cancers according to the anatomy. Distinctions in tissue composition, vascularization and innervations have been clearly identified between the head and body/tail of the pancreas both in embryological development and in histopathology. To understand the postulated genotype difference, we present comprehensive information on two PDAC cell lines as typical representatives originating from pancreatic head and body/tail cancers, respectively.
In the present review, we compare the difference between pancreatic head and body/tail cancers regarding clinical parameters and introducing an in vitro model.
Increasing evidence has shown that tumors at different locations (head vs body/tail) display different clinical presentation (e.g. incidence, symptom), treatment efficiency (e.g. surgery, chemotherapy) and thus patient prognosis. However, the genetic or molecular diversity (e.g. mutations, microRNA) between the two subtypes of PDAC has not been elucidated so far. They present different chemo- and/or radio-resistance, extracellular matrix adhesion and invasiveness, as well as genetic profiles.
Genetic and tumor biological diversity exists in PDAC according to the tumor localization.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.