Components
- F = Fludarabine (purine analog, inhibits DNA synthesis)
- C = Cyclophosphamide (alkylating agent)
- R = Rituximab (anti-CD20 monoclonal antibody)
Indication
- Chronic lymphocytic leukemia (CLL):
- Historically standard frontline therapy for young, fit patients (<65 years) without major comorbidities.
- Still used in IGHV-mutated CLL → can lead to long-term remissions and even functional cure.
- Replaced in many settings by targeted therapies (BTK inhibitors, venetoclax), but remains an option in select patients.
Typical Dosing (28-day cycle × 6 cycles)
- Fludarabine 25 mg/m² IV days 1–3
- Cyclophosphamide 250 mg/m² IV days 1–3
- Rituximab
- Cycle 1: 375 mg/m² IV day 1
- Cycles 2–6: 500 mg/m² IV day 1
Toxicities
- Myelosuppression (severe neutropenia, lymphopenia → infection risk)
- Opportunistic infections (PJP, CMV, HSV) → requires prophylaxis
- Secondary malignancies (MDS/AML risk long-term)
- Immunosuppression: hypogammaglobulinemia, prolonged CD4 suppression
- Infusion reactions (rituximab)
- Hemolytic anemia (rare, autoimmune)
Monitoring / Supportive Care
- CBC with differential, infection signs
- Prophylaxis:
- PJP prophylaxis (e.g., TMP-SMX)
- Antiviral prophylaxis (acyclovir/valacyclovir)
- Consider antifungal in prolonged neutropenia
- Screen for HBV before rituximab (risk of reactivation)
- Vaccination counseling (no live vaccines during and after)
Oncology Pearl
- FCR is no longer the universal frontline standard for CLL.
- It is still considered in young, fit patients with IGHV-mutated CLL and no TP53/17p deletion → can achieve long-term remission (sometimes >10 years).
- In older patients or TP53-mutated disease, targeted therapy (acalabrutinib, zanubrutinib, venetoclax + obinutuzumab) is preferred.