From the Guidelines
Concurrent chemoradiation is generally more suitable than neoadjuvant chemotherapy before radiation therapy for unresectable pancreatic cancer. The standard approach involves gemcitabine (1000 mg/m² weekly) or capecitabine (825-830 mg/m² twice daily on radiation days) given concurrently with radiation therapy, typically delivered as 45-54 Gy in 1.8-2.0 Gy fractions over 5-6 weeks. This concurrent approach offers several advantages: it provides immediate local disease control while simultaneously addressing potential micrometastatic disease, improves radiation efficacy through radiosensitization, and may downstage some tumors to potentially resectable status.
For patients with good performance status, FOLFIRINOX (5-FU, leucovorin, irinotecan, oxaliplatin) or gemcitabine plus nab-paclitaxel can be considered as initial systemic therapy before chemoradiation, especially with high-volume disease or significant symptoms 1. The decision should be individualized based on the patient's performance status, comorbidities, tumor characteristics, and symptom burden.
Some evidence suggests that concurrent gemcitabine and radiation can yield similar or better outcomes when compared with 5-FU–based chemoRT in the setting of locally advanced disease 1. The use of capecitabine as a radiosensitizer has also been assessed in this setting and appears to be effective. Recently reported results of the phase II SCALOP trial showed that health-related quality-of-life scores tended to favor capecitabine-based chemoRT over gemcitabine-based chemoRT 1.
Concurrent chemoradiation is particularly beneficial for local control and pain management, while potentially improving quality of life in these patients with limited treatment options. Systemic chemotherapy followed by chemoRT or SBRT is an option for select patients with unresectable disease and good PS who have not developed metastatic disease 1. However, the international phase III LAP07 RCT found that chemoRT with capecitabine after 4 months of induction chemotherapy provided no survival benefit compared with chemotherapy only 1.
Key points to consider when deciding between concurrent chemoradiation and neoadjuvant chemotherapy before radiation therapy include:
- Patient performance status
- Tumor characteristics
- Symptom burden
- Potential for downstaging tumors to potentially resectable status
- Need for immediate local disease control and pain management
- Potential benefits of radiosensitization and improved radiation efficacy.
From the Research
Comparison of Concurrent Chemoradiation and Neoadjuvant Chemotherapy
- Concurrent chemoradiation and neoadjuvant chemotherapy before radiation therapy (RT) are two approaches used in the treatment of unresectable pancreas cancer.
- A study published in 2006 2 demonstrated the efficacy of concurrent chemoradiation with gemcitabine and 5-fluorouracil (5-FU) in patients with locally advanced, unresectable pancreatic cancer, resulting in an overall response rate of 62.5% and a median survival of 13.6 months.
- Neoadjuvant chemotherapy before RT has also been explored, with a study from 1998 3 suggesting that preoperative chemoradiation is well tolerated and may reduce loco-regional recurrence.
- Another study from 2006 4 investigated the feasibility of preoperative combined radiation therapy and chemotherapy with 5-fluorouracil and cisplatin in potentially resectable pancreatic adenocarcinoma, finding that the proposed pre-operative scheme is feasible and does not prevent successful surgery.
Treatment Outcomes
- The choice between concurrent chemoradiation and neoadjuvant chemotherapy before RT may depend on various factors, including the patient's performance status and the potential for resection.
- A study from 2013 5 highlighted the importance of multi-disciplinary approach in the management of borderline resectable pancreatic cancer, and the potential role of neoadjuvant therapy in downstaging the disease to a resectable state.
- Maintenance therapy with capecitabine after chemoradiation has also been shown to be effective and tolerable in patients with locally advanced unresectable pancreatic adenocarcinoma, with a median overall survival of 17 months 6.
Future Directions
- Further research is needed to determine the optimal treatment approach for unresectable pancreas cancer, including the use of newer agents and technologies such as intensity-modulated radiation therapy.
- The incorporation of novel therapies directed at specific molecular events involved in pancreatic tumorigenesis may also be explored to attempt to reduce systemic relapse 3.