Modified FOLFIRINOX Demonstrates Efficacy in Advanced Gallbladder Cancer


Modified fluorouracil, oxaliplatin, and irinotecan elicited encouraging responses and an acceptable toxicity profile as a frontline treatment for patients with unresectable gallbladder cancer

Atul Sharma, MD, DM

Atul Sharma, MD, DM

Modified fluorouracil, oxaliplatin, and irinotecan (mFOLFIRINOX) elicited encouraging responses and an acceptable toxicity profile as a frontline treatment for patients with unresectable gallbladder cancer, according to findings from a phase 2 study (CTRI/2019/02/017562) published in JCO Global Oncology.

Among 29 evaluable patients, the median overall survival (OS) and progression-free survival was 309 days (10.3 months; 95% CI, 296.92-321.07) and 252 days (8.4 months; 95% CI, 207.96-296.03), respectively. Best response consisted of a complete response (CR; n = 1) and partial responses (PRs; n = 13), translating to an objective response rate (ORR) of 48.2%.

“First-line modified fluorouracil, oxaliplatin, and irinotecan is feasible in unresectable gallbladder cancer with encouraging responses. Toxicities are higher but manageable. Higher response rates make this an option to explore in borderline resectable cases,” Atul Sharma, MD, DM, of All India Institute of Medical Sciences, and coauthors wrote in the study publication.

Gemcitabine plus platinum-based chemotherapy is the standard treatment for patients with unresectable gallbladder cancer. However, outcomes remain poor, and better drug combinations are necessary.

FOLFIRINOX and mFOLFIRINOX have shown improved survival in the metastatic and adjuvant pancreatic cancer settings, respectively. Despite differences in the biology of gallbladder cancer and pancreatic cancer, certain embryologic similarities exist.

As such, investigators launched a pilot study to evaluate the safety and efficacy of mFOLFIRINOX in unresectable or metastatic gallbladder cancer.

To be eligible for the single-arm trial, patients at least 18 years of age had to have histologically confirmed locally advanced unresectable or metastatic gallbladder cancer; an ECOG performance status of 0 or 1; measurable disease; and adequate bone marrow functions defined as hemoglobin above 10 g/dL, total leucocyte count above 4000/mm3 (absolute neutrophil count above 1500/mm3), and platelet count above 1,000,000/mm3; serum creatinine less than 1.8 mg%; and serum bilirubin of 3 or lower mg%.

The eligibility criteria also stipulated that patients had to have hepatic transaminase (serum glutamic-oxaloacetic transaminase [SGOT] and serum glutamic pyruvic transaminase [SGPT]) within 3 times the upper limit of normal (up to 5 times in the case of diffuse liver involvement) and an ECOG performance status of 0 or 1.

Primary end points were OS and ORR.

Treatment consisted of 85 mg/m2 of oxaliplatin, 400 mg/m2 of leucovorin, and 150 mg/m2 of irinotecan, all given once on day 1, plus 2400 mg/m2 of continuous fluorouracil given intravenously over 46 hours in every 2-week-cycles for a maximum of 12 doses. Primary granulocyte colony-stimulating factor prophylaxis was also mandated on days 4, 6, and 8 of each cycle.

Between February 2019 and July 2020, 29 patients with unresectable gallbladder cancer were enrolled. The median age was 52 years, and 18 patients were female. Most patients had an ECOG performance status of 1 (n = 25). Five patients had bilirubin greater than normal, and 15 patients each had high serum alkaline phosphatase and carbohydrate antigen 19-9. Twenty-five patients had stage IV disease, and the remaining patients had unresectable locally advanced disease.

Additional results indicated that the median OS of patients who achieved a CR or PR was 413 days (13.76 months; 95% CI, 266.59-559.40).

A median of 8.5 cycles of therapy was given, and 11 patients completed all 12 cycles of treatment. Nine patients stopped chemotherapy due to disease progression, and one because of toxicity. Treatment is ongoing in 3 patients.

Twenty-two patients required dose reductions. A treatment delay of 1 to 2 weeks was seen in 25 patients.

Nine patients experienced stable disease. Four patients with metastatic disease underwent R0 resection.

As of the cutoff date, 9 remain alive, 3 of whom remain disease free. Eighteen patients died of progressive disease, and in 2 patients the cause of death was unknown.

In terms of safety, no deaths occurred. Twenty-three patients experienced grade 3/4 toxicity, common ones of which included diarrhea (n = 13), vomiting (n = 12), and anemia (n = 7).

“Phase 3 studies are needed to compare this [regimen] with gemcitabine and platinum and also to explore its utility as neoadjuvant therapy in borderline resectable cases,” concluded the study authors.


  1. Sharma A, Pramanik R, Kumar A, et al. Safety and efficacy of modified FOLFIRINOX in unresectable or metastatic gallbladder cancer: a phase II pilot study. JCO Glob Oncol. 2021;7:820-826. doi:10.1200/GO.20.00657
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