Current therapeutic strategies for advanced pancreatic cancer: A review for clinicians

Abstract

Pancreatic cancer (PC) would become the second leading cause of cancer death in the near future, despite representing only 3% of new cancer diagnosis. Survival improvement will come from a better knowledge of risk factors, earlier diagnosis, better integration of locoregional and systemic therapies, as well as the development of more efficacious drugs rising from a deeper understanding of disease biology. For patients with unresectable, non-metastatic disease, combined strategies encompassing primary chemotherapy and radiation seems to be promising. In fit patients, new polychemotherapy regimens can lead to better outcomes in terms of slight but significant survival improvement associated with a positive impact on quality of life. The upfront use of these regimes can also increase the rate of radical resections in borderline resectable and locally advanced PC. Second line treatments showed to positively affect both overall survival and quality of life in fit patients affected by metastatic disease. At present, oxaliplatin-based regimens are the most extensively studied. Nonetheless, other promising drugs are currently under evaluation. Presently, in addition to surgery and conventional radiation therapy, new locoregional treatment techniques are emerging as alternative options in the multimodal approach to patients or diseases not suitable for radical surgery. As of today, in contrast with other types of cancer, targeted therapies failed to show relevant activity either alone or in combination with chemotherapy and, thus, current clinical practice does not include them. Up to now, despite the fact of extremely promising results in different tumors, also immunotherapy is not in the actual therapeutic armamentarium for PC. In the present paper, we provide a comprehensive review of the current state of the art of clinical practice and research in PC aiming to offer a guide for clinicians on the most relevant topics in the management of this disease.

The concept of ‘borderline resectable’ pancreatic cancer: limited foundations and limited future?

“…The best chance of survival is by surgical resection (2,3) although the chilling reality is that a curative surgical resection (i.e., negative margins or R0) is only possible in a fifth of patients of whom only 20% are alive at 5 years (4). Despite this, a surgery-first approach remains the cornerstone of curative treatment for only a minority of patients with resectable disease because resection has become more safe (5) and effective systemic treatments are still awaited (6). It is no surprise that in the drive to achieve better results some surgeons advocate more radical surgery to treat more patients (7)(8)(9).…”

Scientific rationale for integrative and personalised strategies for pancreatic ductal adenocarcinoma management

“…For both sexes, there has been a steady increase in incidence over the past 20 years [3,5]. The dismal outlook of this disease is mostly due to the majority (~80 %) of patients being diagnosed with advanced-stage disease, with severe cachexia and poor metabolic status rapidly contributing to morbidity and mortality [6]. Currently, there is no effective screening and no early detection method available to diagnose PDAC at a pre-malignant stage.…”

“…Currently, there is no effective screening and no early detection method available to diagnose PDAC at a pre-malignant stage. Although surgery to remove pancreatic tumours offers the best chance for survival, only a minority (10-15 %) of patients can undergo curative operation at the time of diagnosis [6]. Even after surgery, the overall 5-year survival rate is less than 4% mainly because micrometastases will already have been established, eventually leading to local and/or systemic recurrence [3].…”

Arterial Chemoinfusion in Patients With Locally Advanced and Metastatic Pancreas Cancer

“…Стандартом лечения больных с неоперабельным РПЖ является монохимиотерапия гемцитабином, но при этом частота ответа составляет лишь 5-15% [5,11]. Попытки комбинации гемцитабина с оксалиплатином, другими цитостатиками или таргетными препаратами не показали значительного улучшения результатов: медиана выживаемости больных составляет менее 6 мес, а однолетняя выживаемость -менее 18% [9,14,15].…”