**6. Locally advanced and unresectable disease**

Locally advanced unresectable and metastatic pancreatic cancer patients have a similar dismal prognosis. In case of patients with a good performance status (ECOG 0–1), they should be strongly considered for treatment with high-intensity palliative chemotherapy, with the aim of improving quality of life and overall survival. Conroy et al. showed in the PRODIGE trial that FOLFIRINOX regimen when compared with gemcitabine was associated with a significative better survival, with a reported median overall survival of 11.1 months versus 6.8 months, respectively (HR for death 0.57 (95% CI, 0.45–0.73), p < 0.001) [30]. This trial was basically conducted among French population and did not include patients of 76 years or older. In patients with ECOG 2 and those with ECOG 0–2 older than 75 years, a lower intensity chemotherapy regimen like gemcitabine with or without nab-paclitaxel should be considered. Von Hoff et al. published in 2013 that the combination of gemcitabine and nab-paclitaxel improves overall survival compared with gemcitabine alone (median OS 8.5 vs. 6.7 months, HR 0.72, CI 0.62–0.83, P < 0.001) [31]. Patients older than 75 years were also included in this study. Chemotherapy should not be recommended in patients with a poor performance status (ECOG 3–4) due to lack of benefit and because a higher risk of toxicity with worsening of quality of life.

was 26 months for the neoadjuvant group and 21 months for the group who underwent surgery as an upfront treatment, but also a higher pathological tumor stage, a higher incidence of lymph node compromise, and a lesser R0 resection in the group that did not receive neoadjuvant treatment were seen. A two-arms Markov model showed that the median overall survival was longer for the neoadjuvant cohort (22 months) in comparison with the adjuvant group (20 months) [37]. Despite this information that shows better outcomes in terms of survival when neoadjuvant treatments have been done, to date, there are no phase 3 randomized clinical trials that support the use of neoadjuvant treatments in pancreatic cancer patients. Most of the available data are limited to retrospective evidence or to one-arm design-prospec-

Neoadjuvant Treatment for Nonmetastatic Pancreatic Cancer

http://dx.doi.org/10.5772/intechopen.75739

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In recent years, the use of systemic preoperative chemotherapy alone or in combination with radiation therapy has been offered to an increasing number of patients with the main intention of reducing the size of the tumor, increasing the likelihood of negative resection margins,

Phase 2 clinical trials have evaluated the use of neoadjuvant therapy for resectable and borderline resectable pancreatic cancer patients, either with chemotherapy or with chemoradio-

One quarter of the patients who underwent neoadjuvant chemoradiotherapy had disease progression, and surgery was not performed. Disparities on reported results among patients who underwent surgery showed an R0 resection rate between 12.5 and 96% of the total resected patients. Patients who had progression after treatment did it mainly with distance metastasis (59–73%), most of them located at the liver. Local recurrence rate was seen between 0 and 25% according to different reports. Reported overall survivals show also differences; patients who only received neoadjuvant treatment with chemoradiation had reported survival between 8 and 34 months; patients who underwent only neoadjuvant chemotherapy achieved survivals

Chemotherapy without radiation has been explored as an option for neoadjuvant treatment in pancreatic cancer. A phase 2 clinical trial in the neoadjuvant setting using gemcitabine with or without cisplatin showed a resection rate of 54% and a median overall survival of 28 months in resected patients [40]. Unfortunately, similar trials using gemcitabine plus cisplatin doublet showed inferior results [41]. Due to the heterogeneity of these studies that included different types of patients such as resectable, borderline resectable, and unresectable patients at diagnosis, but also that have used different modalities of radiotherapy and different schedules and schemes of chemotherapy, no conclusion can be drawn regarding the overall impact on survival and what are the most effective chemotherapy agents or the best

Since 2011, after the results of PRODIGE trial, many case series with neoadjuvant FOLFIRINOX for locally advanced pancreatic cancer have been published, but sample sizes of most studies have been too small to draw definitive conclusions about the efficacy and safety of this treatment approach; however, its use followed by chemoradiation as a multimodality treatment

combination of chemotherapy agents for resectable pancreatic cancer.

has shown promising results (**Table 2**).

and testing the effects of cytotoxic medications in vivo [39].

tive clinical trials [38].

therapy combination (**Table 1**).

up to 19 months.
