Chemotherapy to Treat Chronic Lymphocytic Leukemia (CLL)
Chemotherapy for CLL may be postponed if the patient has early-stage disease and shows no related symptoms. If necessary, induction chemotherapy may be started with an alkylating agent such as chlorambucil or cyclophosphamide. If the physician suspects the existence of autoimmune (against the person's own body) blood problems, a corticosteroid (e.g., prednisone) may also be used.
Option 1: Chemotherapy with chlorambucil (Leukeran) or cyclophosphamide (Neosar) plus prednisone, if needed
- How are they given:
- Chlorambucil: orally
- Cyclophosphamide: IV or orally
- Prednisone: orally
- What is the duration:
- Chlorambucil: 4 days every month
- Cyclophosphamide: every 2 to 5 days, or by another schedule
- Prednisone: daily for 14 days, tapering off over 2 more weeks
- What are the side effects:
- Chlorambucil - bone marrow toxicity;
- Cyclophosphamide - infertility, severe bladder inflammation, cardiotoxicity (heart damage), immune system suppression, hair loss
- Prednisone - immune system effects
Research suggests that combination chemotherapy with cyclophosphamide, vincristine, and prednisone (COP) is no more effective than chlorambucil alone in achieving remission or prolonging survival. Perhaps more importantly, the neurotoxicity (nerve-damaging effects) of vincristine may make it an unacceptable choice for elderly patients. Clinical trials in later-stage CLL patients have reported some responses from combination chemotherapies that include an anthracycline drug like doxorubicin (Adriamycin, Rubex) (e.g., chlorambucil, doxorubin, and prednisone, or CAP; cyclophosphamide, vincristine, doxorubicin, and prednisone, or CHOP).
In recent years, a class of compounds known as purine analogs have been developed for the treatment of CLL. Three such drugs—fludarabine (arabinofuranosyl-2-fluoroadenine-5'-monophosphate), pentostatin (2-deoxycoformycin), and cladribine (2-chlorodeoxyadenisine; 2-CDA)—have been tested as single-agent treatments against CLL. These drugs usually are reserved for cases in which CLL is resistant (unresponsive to treatment) or returns after chemotherapy with chlorambucil or cyclophosphamide.
Option 2: Chemotherapy with fludarabine phosphate (Fludara®), pentostatin (2-deoxycoformycin; "DCF"; Nipent)*, or cladribine (2-chlorodeoxyadenosine; "2-CDA"; Leustatin) **Not FDA-approved for the treatment of CLL
- How are they given:
- Fludarabine: 30-minute infusion intravenously (IV), the drug is delivered into the veins
- Pentostatin: bolus infusion IV
- Cladribine: continuous infusion IV or 2-hour infusion IV
- What is the duration:
- Fludarabine: 5 days every 28 days
- Pentostatin: weekly
- Cladribine: 5-7 days every 28 days
- What are the side effects: For all purine analogs–myelotoxicity (bone marrow damage), neutropenia (granulocytopenia; too few mature granulocytes; bacteria-destroying white blood cells that contain small granules), neurotoxicity (nervous system damage), immunosuppression (prevention of the immune response), fever, and infection
Alemtuzumab (Campath) may be used in patients with B-cell CLL that does not respond to these other chemotherapy regimens. This medication is adminstered via IV infusion and may cause serious adverse effects, including severe bone marrow supression (causing reduced levels of all blood components; called pancytopenia) and decreased platelet and red blood cell levels.
In March 2008, the Food and Drug Administration (FDA) approved the chemotherapy drug bendamustine hydrochloride (Treanda) to treat chronic lymphocytic leukemia. This drug, which is administered by injection, may help slow progression of the disease. Side effects include neutropenia, thrombocytopenia, anemia, nausea, and fever.
In November 2013, the FDA approved obinutuzumab (Gazyva) for use in combination with chlorambucil to treat people with previously untreated CLL. This drug helps certain cells in the immune system attack cancer cells in the body. In clinical studies, obinutuzumab provided a significant improvement in disease-progression-free survival—from an average of 11.1 months with chloraibucil alone to 23 months, on average.
Common side effects of this medication include infusion-related reactions, low blood cell counts, bone and muscle pain, and fever. Gazyva contains a Boxed Warning due to an increased risk for hepatitis B reactivation and a serious condition called progressive multifocal leukoencephalopathy (rare disorder that causes damaging lesions in the brain).
In February 2014, ibrutinib (Imbruvica) was approved to treat people with CLL whose disease has progressed in spite of previous treatment. According to the FDA, this drug works by blocking an enzyme that allows cancer cells to grow and divide. Clinical study results show that cancer shrinks in 58 percent of patients treated with ibrutinib. Side effects include:
- Diarrhea, constipation
- Low blood cell count (e.g., anemia, neutropenia, thrombocytopenia)
- Mouth sores
- Muscle pain, bone pain
- Respiratory infection
- Swelling (edema)