A Novel Approach: Aggressive Chemotherapy Regimen Before Surgery in Resectable Pancreatic Adenocarcinoma

Twenty percent of the annual cases of pancreatic ductal adenocarcinoma (PDA) in the U.S. will present as resectable disease. Yet even those cases — 10,000 out of the approximately 50,000 diagnoses of PDA of each year — remain lethal malignancies.

The current standard of care — surgical resection followed by adjuvant chemotherapy — results in suboptimal outcomes: median overall survival (OS) is, at best, 28 months. Additionally, clinical series show 70-85 percent of patients die of systemic, as opposed to locoregional, recurrence.

A national team led by Davendra P.S. Sohal, MD, MPH, Director of the Clinical Genomics Program at Cleveland Clinic’s Taussig Cancer Center, believes a different approach may work better: administering multi-agent chemotherapy before surgery when patients are better able to withstand such aggressive treatments.

Enrolling patients in phase 2 trial

To test this theory and to find the best drug regimen, the team is enrolling PDA patients in S1505, a phase 2 trial run by SWOG through the National Clinical Trials Network of the National Cancer Institute.

The study, which was accepted for presentation at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, will measure overall survival (OS) in patients who preoperatively receive either mFOLFIRINOX or gemcitabine/nab-paclitaxel.

“We are testing a novel approach to give chemotherapy up front, using more aggressive chemotherapy regimens than the standard,” says Dr. Sohal. “Our hope is that we improve patients’ clinical outcomes by using these more aggressive chemotherapies before surgery when patients are in a better condition to tolerate them.”

Patient eligibility requirements

Qualifications for the trial, which will include up to 150 patients, are as follows:

*Patients must be adults with an ECOG PS of 0 or 1.

*Patients must have a confirmed histophatologic diagnosis of PDA and resectable disease as confirmed by central radiology review.

In addition:

*Tumors can have no involvement of the celiac, common hepatic or superior mesenteric arteries (and if present, variants).

*There can be no involvement, or < 180 degree interface between tumor and vessel wall, of the moral or superior mesenteric veins;

*There can be no evidence of metastatic disease.

*Patient must have adequate bone marrow, hepatic and renal function.

*Patient must be treatment-naive (no surgery, radiation, systemic therapy) for index cancer.

Regimen with best results tested again in future trial

Patients will receive 12 weeks of treatment — either six doses of mFOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin, without bolus 5-FU and leucovorin), or nine doses of gemcitabine/nab-paclitaxel, on standard schedules — of preoperative chemotherapy, followed by surgical resection and 12 weeks of identical postoperative chemotherapy.

Dr. Sohal and colleagues hope to establish the safety of this approach to treatment and find the drug combination that is most effective and increases patients’ overall survival. If one regimen works better than the other, then they can further test that regimen in novel combinations.

“When we do standard treatment for resectable PDA, surgery followed by one chemotherapy drug, overall survival is barely two years,” Dr. Sohal says. “So we hope to improve on that. Nevertheless, this remains a difficult disease.”