Can Fludarabine, Nelarabine, or Etoposide Cause Pancreatitis?
None of these three chemotherapy agents—fludarabine, nelarabine, or etoposide—are established causes of pancreatitis based on current evidence.
Evidence Assessment
Fludarabine
- Fludarabine is not listed among medications with documented associations with pancreatitis in comprehensive drug-induced pancreatitis reviews 1, 2, 3.
- The agent is classified as having low gonadotoxicity risk but has no documented pancreatitis risk in major oncology guidelines 4.
- Multiple studies examining fludarabine-based regimens (FCR, CFAR, OFAR) in chronic lymphocytic leukemia and lymphomas do not report pancreatitis as a significant adverse event 4.
Nelarabine
- Nelarabine is not identified as a cause of pancreatitis in systematic reviews of drug-induced pancreatitis 1, 2, 3.
- The drug is recommended in nelarabine-containing regimens for relapsed T-cell acute lymphoblastic leukemia without pancreatitis warnings 4.
- No pancreatitis association appears in published treatment protocols utilizing nelarabine 4.
Etoposide
- Etoposide is not classified among medications causing pancreatitis in evidence-based reviews that categorize drugs by strength of evidence 1, 3.
- The agent is listed as having low gonadotoxicity risk with no mention of pancreatic toxicity 4.
- Etoposide is a standard component of HLH treatment protocols and lymphoma regimens without documented pancreatitis risk 4.
Clinical Context
Established High-Risk Medications
For comparison, medications with strong evidence (Class I) for causing pancreatitis include 1:
- Azathioprine and mercaptopurine (4% incidence in IBD patients) 5
- Didanosine (documented fatal cases) 5
- Asparaginase
- Valproic acid
- L-asparaginase (notably used in ALL protocols alongside these agents) 4
Important Caveats
- Cancer patients receiving chemotherapy may develop pancreatitis from other causes, including the malignancy itself, infections (particularly in immunosuppressed states), or concomitant medications 4, 2.
- Drug-induced pancreatitis has an estimated incidence of only 0.1-2% of all acute pancreatitis cases 2.
- Hemophagocytic lymphohistiocytosis (HLH) associated with malignancies can present with pancreatic involvement, which may be confused with drug toxicity 4.
- Patients receiving these agents often receive multiple concurrent medications, making causality assessment challenging 1, 2.
Diagnostic Approach
If pancreatitis develops in a patient receiving these agents 3:
- Exclude common etiologies (gallstones, alcohol, hypertriglyceridemia)
- Review all concurrent medications, particularly those with established pancreatitis risk
- Consider infectious triggers, especially in neutropenic patients 4
- Evaluate for underlying malignancy-related causes
- Document temporal relationship between drug initiation and symptom onset