Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline

Abstract

Purpose To provide evidence-based recommendations to oncologists and others for the treatment of patients with metastatic pancreatic cancer. Methods American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts to conduct a systematic review of the literature from April 2004 to June 2015. Outcomes were overall survival, disease-free survival, progression-free survival, and adverse events. Results Twenty-four randomized controlled trials met the systematic review criteria. Recommendations A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. Goals of care, patient preferences, treatment response, psychological status, support systems, and symptom burden should guide decisions for treatments. A palliative care referral should occur at first visit. FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin; favorable comorbidity profile) or gemcitabine plus nanoparticle albumin-bound (NAB) -paclitaxel (adequate comorbidity profile) should be offered to patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 based on patient preference and support system available. Gemcitabine alone is recommended for patients with ECOG PS 2 or with a comorbidity profile that precludes other regimens; the addition of capecitabine or erlotinib may be offered. Patients with an ECOG PS ≥ 3 and poorly controlled comorbid conditions should be offered cancer-directed therapy only on a case-by-case basis; supportive care should be emphasized. For second-line therapy, gemcitabine plus NAB-paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX, an ECOG PS 0 to 1, and a favorable comorbidity profile; fluorouracil plus oxaliplatin, irinotecan, or nanoliposomal irinotecan should be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, ECOG PS 0 to 1, and favorable comorbidity profile, and gemcitabine or fluorouracil should be offered to patients with either an ECOG PS 2 or a comorbidity profile that precludes other regimens. Additional information is available at www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki .

A drug‐repositioning screen for primary pancreatic ductal adenocarcinoma cells identifies 6‐thioguanine as an effective therapeutic agent for TPMT‐low cancer cells

“…Moreover, there is a desmoplastic reaction, which means accumulation of the extracellular matrix along with activated (fibrotic) stellate cells (Bahrami et al ., 2017), resulting in a barrier to drug delivery (Lunardi et al ., 2014). Despite these challenges, there are newly developed therapeutic options, including FOLFIRINOX and Paclitaxel‐Nab, that have shown progress in chemotherapy (Sohal et al ., 2016). Yet, there is a desperate need for an effective therapeutic agent to extend the survival of more patients with PDAC.…”

Irinotecan Liposome Injection

“…24 The irinotecan liposome combination regimen is consistent with current guideline-recommended second-line therapies. 21 Data are not available directly comparing this regimen with other recommended regimens (eg, fluorouracil plus oxaliplatin or irinotecan) after a first-line gemcitabine-based regimen.…”

Current status on the place of FOLFIRINOX in metastatic pancreatic cancer and future directions

“…17 To our knowledge, no head-to-head clinical trials comparing these two new regimens have been published and interstudy comparisons are inherently limited. The main results of the two pivotal trials are presented in Table 1.…”

“…45 According to the ASCO clinical practice guidelines, GnP may be an appropriate option for second-line therapy in patients who experience disease progression following first-line treatment with FOLFIRINOX. 17,45 Single-agent gemcitabine or inclusion into a clinical trial may also be considered for patients with a well-preserved PS. 46 …”

“…Therefore, the National Comprehensive Cancer Network, American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) guidelines recommend FOLFIRINOX for metastatic pancreatic adenocarcinoma (MPA) patients with either 0 or 1 ECOG PS and a favorable comorbidity profile. [15][16][17][18][19][20] All guidelines state the mandatory assessment of patients in terms of their condition and comorbidities in order to offer appropriate treatment with a safe toxicity profile. Despite this, the FOLFIRINOX regimen exhibits a specific profile of toxicity among distinct populations.…”