LEUKEMIA

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Chemotherapy


Chemotherapy

Chemotherapy is a general term that is used to describe cancer-killing drugs. Such drugs can be given intravenously, through a vein; orally, by mouth; subcutaneously, injected under the skin; intramuscularly, injected into a muscle; or intrathecally, injected into the cerebrospinal fluid (CSF).

Chemotherapy for leukemia is varied, because there are many different forms of this disease. In general, though, leukemia treatment relies on combination chemotherapy with a number of different anticancer drugs. Such drugs destroy cancer cells by preventing them from growing and dividing rapidly. Unfortunately, a number of the body's normal, noncancerous cells also divide rapidly and therefore are harmed by chemotherapy. Specifically, the hair follicles, red and white blood cells, blood-clotting platelets, and cells that line the gastrointestinal system may be damaged or destroyed, causing side effects. Such side effects depend upon the type and dose of drugs taken, as well as the length of time that they are used.

Chemotherapeutic side effects may include temporary hair loss, mouth sores, anemia (decreased numbers of red blood cells that may cause fatigue, dizziness, and shortness of breath), leukopenia (decreased numbers of white blood cells that may lower resistance to infection), thrombocytopenia (decreased numbers of platelets that may lead to easy bleeding or bruising), and gastrointestinal symptoms like nausea, vomiting, and diarrhea.

Tumor lysis syndrome is a specific side effect of leukemia therapy that occurs when there is a rapid breakdown of leukemia cells due to chemotherapeutic drugs. The cells split apart and release cell fragments, metabolic byproducts, and minerals into the bloodstream. These substances can damage the kidneys, heart, and nervous system. Therefore, physicians often monitor acute leukemia patients for this syndrome. They may prescribe fluids, sodium bicarbonate, and allopurinol (a drug used to reduce uric acid in the blood) to rid the body of unwanted chemicals and cell remains.

Acute Myelogenous Leukemia (AML)
Perhaps the most common drug treatment plan AML is the combination of 3 days of an anthracycline (e.g., daunorubicin, doxorubicin) and 7 days of ara-C. This plan is known as the three plus seven method. Some oncologists also add the drug 6-thioguanine to the mix (see option 2), although most studies indicate that this agent does not improve the rates or length of remission.

Please Note: The option number does not imply that one regimen is superior over another.

Option 1: Chemotherapy with daunorubicin (Cerubidine®) or doxorubicin (Adriamycin®), plus cytarabine (ara-C;Cytosar-U®); also called "DA"

  • How is it given:
    • Daunorubicin: intravenously (IV), the drug is delivered into the veins
    • Doxorubicin: IV
    • Cytarabine: IV
  • What is the duration: Given as 3 days of anthracycline (daunorubicin, doxorubicin, etc.) plus 7 days of cytarabine
  • What are the side effects: Daunorubicin - myelosuppression (impaired bone marrow function), cardiotoxicity (heart damage), gastrointestinal effects; doxorubicin - cardiotoxicity, worsening of symptoms caused by other drugs; cytarabine - gastrointestinal effects (nausea, vomiting, diarrhea), bleeding, fever
Option 2: Chemotherapy with daunorubicin (Cerubidine®) or doxorubicin (Adriamycin®), cytarabine (ara-C; Cytosar-U®), and 6-thioguanine (Tabloid®); also called "DAT"

Option 3: Chemotherapy with cytarabine (ara-C; Cytosar-U®) and idarubicin (Idamycin®)

Option 4: Chemotherapy with mitoxantrone (Novantrone®) and etoposide (VePesid®) **not FDA-approved for the treatment of leukemia

Option 5: Chemotherapy with amsacrine (AMSA), cytarabine (ara-C; Cytosar-U®), and 6-thioguanine (Tabloid®). Individuals with the M3 subtype of AML - otherwise known as promyelocytic leukemia (PML) - benefit most from a special form of induction therapy using the drug all-trans retinoic acid (ATRA). In particular, patients who have genetic translocations of chromosomes 15 and 17 exhibit marked changes in their leukemic cells after ATRA therapy. ATRA induces terminal differentiation (maturation) of the leukemic cells and restored blood formation.

Option 6: Chemotherapy with all-trans retinoic acid (ATRA)

  • How is it given: Orally
  • What are the side effects: Hyperleukocytosis (increased number of white blood cells); syndrome of respiratory distress, fever, weight gain, edema, and pleural effusion (build-up of fluid within the pleura - the membranes that line the outer lungs and chest cavity) known as ATRA syndrome or retinoic acid syndrome

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Chronic Myelogenous Leukemia (CML)
The chemotherapeutic options for CML are as follows:

Option 1: Chemotherapy with hydroxyurea (Hydrea®)

  • How is it given: Orally
  • What is the duration: 6-week trial, followed by treatment of indefinite length
  • What are the side effects: Sore mouth, mouth ulceration, nausea, diarrhea, rashes, bone marrow changes
Option 2: Chemotherapy with busulfan (Myleran®)
  • How is it given: Orally
  • What is the duration: usually 12-20 weeks
  • What are the side effects: Myelosuppression (impaired bone marrow function), sterility in men and women, early menopause, skin pigmentation, cataracts, respiratory failure ("busulfan lung")

Acute Lymphocytic Leukemia (ALL)
Chemotherapy for ALL usually begins with a three-drug schedule such as:

Option 1: Chemotherapy with prednisone, vincristine sulfate (Oncovin®), and an anthracycline drug (e.g., daunorubicin)

  • How is it given: Prednisone is given orally in three divided doses versus Vincristine is given intravenously (IV), the drug is delivered into the veins.
  • What is the duration: Prednisone and vincristine are given at weekly intervals for 4 weeks
  • What are the side effects: Vincristine - hair loss, nervous system effects

Option 2: Chemotherapy with prednisone. vincristine (Oncovin ®), and L-asparaginase (Elspar®) or cyclophosphamide (Cytoxan®)

  • How is it given:
    • Prednisone: orally
    • Vincristine: Intravenously (IV), the drug is delivered into the veins
    • L-asparaginase: IV or intramuscularly; subcutaneously, injected under the skin; or IV (least favorable due to allergic reactions with this route)
    • Cyclophosphamide: IV or orally
  • What is the duration: Prednisone and vincristine are given at weekly intervals for 4 weeks; the schedule for L-asparaginase is more variable. Cyclophosphamide is given every 2 to 5 days, or by another schedule.
  • What are the side effects:
    • Prednisone - immune system effects
    • Vincristine - hair loss, nervous system effects
    • L-asparaginase - anaphylactic (severe allergic) reactions, pancreas inflammation, blood clotting problems
    • Cyclophosphamide - infertility, severe bladder inflammation, cardiotoxicity (heart damage), immune system suppression, hair loss
Consolidation therapy for ALL (1-3 months in adults; 4-8 months in children) may involve treatment with combination chemotherapy or antimetabolites such as methotrexate and 6-mercaptopurine (6-MP):

Option 1: Chemotherapy with prednisone, vincristine (Oncovin®), L-asparaginase (Elspar®) and daunorubicin, followed by Cyclophosphamide (Cytoxan®), cytarabine (ara-C; Cytosar-U®), and 6-thioguanine (Tabloid®)

Option 2: Chemotherapy with methotrexate sodium plus 6-mercaptopurine (6-MP; Purinethol®)

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Chronic Lymphocytic Leukemia (CLL)
Chemotherapy for CLL may be postponed if the patient has early-stage disease and shows no related symptoms (see Treatment of Leukemia). Yet, 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 like prednisone may be added to the mix.

Option 1: Chemotherapy with chlorambucil (Leukeran®) or cyclophosphamide (Cytoxan®) 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 better 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. Yet 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
Hairy Cell Leukemia (HCL)
Most newly diagnosed patients with HCL will receive chemotherapy with a purine analog.

Option 1: Chemotherapy with cladribine (2-chlorodeoxyadenosine; 2-CDA; Leustatin®)

  • How is it given: Continuous infusion intravenously (IV), the drug is delivered into the veins
  • What is the duration: 7 days
  • What are the side effects: Dose-related neutopenia (granulocytopenia; too few mature granulocytes; bacteria-destroying white blood cells that contain small granules), myelotoxicity (bone marrow damage), neurotoxicity (nervous system damage), immunosuppression (prevention of the immune response), fever, and infection

Option 2: Chemotherapy with pentostatin (2-deoxycoformycin; "DCF"; Nipent®)

  • How is it given: Bolus (concentrated dose) infusion intravenously (IV), the drug is delivered into the veins
  • What is the duration: Once every 14 days until maximum response is obtained
  • What are the side effects: Dose-related neutopenia (granulocytopenia; too few mature granulocytes; bacteria-destroying white blood cells that contain small granules), myelotoxicity (bone marrow damage), neurotoxicity (nervous system damage), immunosuppression (prevention of the immune response), fever, and infection.
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