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The chemotherapy regimen known as FOLFIRINOX produces an "impressive clinical response" in locally advanced pancreatic ductal adenocarcinoma, according to the authors of a new small, retrospective, cohort study.
This chemotherapy regimen has been shown to improve survival in phase 3 trials of patients with metastatic disease but is relatively untested in this earlier setting, say the investigators from the University of Pittsburgh in Pennsylvania, led by Brian Boone, MD, a resident in the department of surgery.
Dr. Boone presented a study of the neoadjuvant use of FOLFIRINOX in patients with locally advanced disease today here at the Society of Surgical Oncology (SSO) 66th Annual Cancer Symposium.
FOLFIRINOX is the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin. Between February 2011 and September 2012, the multidrug regimen was recommended for 25 patients at Pittsburgh's Pancreatic Cancer Specialty Care Center. Their locally advanced disease had rendered 13 of the patients (52%) unresectable and 12 (48%) borderline resectable.
Ultimately, 4 of the 25 patients did not undergo the treatment and 21 patients (84%) were treated preoperatively with a median of 5 cycles.
With regard to the study's primary outcomes, Dr. Boone said that FOLFIRINOX treatment was impressive.
First, 13 (62%) of the 21 treated patients demonstrated a Ca 19-9 response, a tumor marker commonly used to assess treatment response in pancreatic cancer. Second, 8 (38%) of the patients had an R0 resection (including 2 patients from the "unresectable" group). This rate is consistent with other single-center series in which chemotherapy has been used neoadjuvantly in locally advanced disease, Dr. Boone said.
Finally, 2 (18%) of the patients had a complete pathologic response. If this rate holds up in a larger, prospective clinical trial, it would be dramatic because, historically, only 2% to 3% of pancreatic cancer patients treated with gemcitabine, which has been a standard treatment, have had such a response, Dr. Boone said.
The multidrug treatment was well tolerated. One third of patients had a dose reduction and a little less than a third had treatment delays. Four patients (19%) needed hospital admission due to adverse events during treatment. There were only a few grade 4 events; 5% of the patients had this high grade of neutropenia and 5% had this grade of leukopenia.
Also, 15 patients received additional chemotherapy and/or radiation therapy prior to surgical exploration, which muddied the results somewhat, Dr. Boone admitted.
A total of 13 patients underwent surgical exploration. Seven (64%) of those underwent pancreaticoduodenectomy, 2 (18%) underwent distal pancreatectomy, and 2 (18%) underwent total pancreatectomy. Widespread peritoneal metastases were discovered at the time of surgery in 2 (8%) patients.
"FOLFIRINOX alone or as part of multimodality approach is a biologically active regimen in locally advanced pancreatic ductal adenocarcinoma," the authors concluded in their abstract.
More on Toxicity
The investigators were inspired to do their study in locally advanced disease because trials of FOLFIRINOX in metastatic pancreatic ductal adenocarcinoma have demonstrated dramatic results.
In a landmark study published in 2011, FOLFIRINOX provided the best survival time ever reported in metastatic pancreatic cancer. Overall survival was significantly better with FOLFIRINOX than with gemcitabine (11.1 vs 6.8 months; P < .0001).
However, "significant toxicity" is a concern with FOLFIRINOX in any setting, the authors of this new study state in their abstract.
Indeed, Dr. Boone told Medscape Medical News that the toxicity reported in their new study of the multidrug regimen was an understatement. "I definitely think that we underestimated the toxicity because our study is a retrospective chart review," he said.
Also, notably, the median age of the 25 patients in the new study was 59 years. FOLFIRINOX is generally only administered to younger pancreatic cancer patients with a good performance status, Dr. Boone said.
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Recently, another clinician echoed this comment during a press conference preceding the 2013 Gastrointestinal Cancers Symposium.
Kenneth Yu, MD, from the Memorial Sloan-Kettering Cancer Center in New York City, said that at his center, "FOLFIRINOX remains the treatment of choice for our pancreatic cancer patients who are relatively fit." However, he acknowledged the need for "judicious adjustment in dosing" with the regimen. Also, "most" patients are less robust and therefore not candidates for the multidrug regiment, he explained.
Please know that my personal opinion is not intended nor implied to be a substitute for professional medical advice. If provided, information are for educational purposes.Consult doctor is a MUST for changing of treatment plans.