Conventional Chemotherapy

Conventional Chemotherapy for CML In Chronic Phase

Chemotherapy (along with other approaches such as radiation therapy and P32) has been used for many years in the treatment of CML. Chemotherapeutic agents have generally been employed to control WBC counts and symptoms during the chronic phase of CML. Unfortunately, they have little effect on the progression of disease to its final and fatal phase: blast crisis. The most widely used chemotherapeutic agents for the control of chronic phase CML are busulfan and hydroxyurea.

 

Busulfan

  • Busulfan (Myleran, GlaxoSmithKline) was first used to treat CML in the 1950s.

  • Randomised trials demonstrated that busulfan was superior to radiation therapy and P32, producing better disease control for longer periods. Thus, after its introduction, busulfan replaced these treatments.
  • The drug is given orally.
  • It is currently indicated for the palliative treatment of CML.

  • Busulfan has serious side-effects:
    • Severe prolonged myelosuppression in 10% of patients
    • Idiosyncratic pulmonary reactions
    • Marrow fibrosis
    • Endocardial fibrosis

While most (90%) patients treated with busulfan experience a haematological response, a CHR is not often achieved. Typically, patients are treated with adequate amounts of medication to achieve relief of symptoms and a PHR, with WBC counts of 2050 x 109/L. There is no evidence that treatment with busulfan affects disease progression. The use of busulfan prior to SCT has been shown to have an adverse effect on post-transplant survival. Because hydroxyurea produces similar or better results with less toxicity, it has generally replaced busulfan in clinical practice.

 

 

Hydroxyurea

  • Hydroxyurea (Hydrea or Litalir in some countries, Bristol-Myers Squibb Oncology) was introduced for the treatment of CM in 1972.
  • Hydroxyurea is indicated for the treatment of CML and several other malignancies.
  • Hydroxyurea therapy is superior to busulfan in CML:
  • A large randomised study of 458 patients with CML in chronic phase found that patients treated with hydroxyurea had a significantly longer median survival.
  • This survival advantage was present in all prognostic sub-groups.
  • Hydroxyurea has a better toxicity profile than busulfan.
  • It provides rapid but more transient control of haematological manifestations and thus requires frequent follow-up.

  • Its main side-effects include:
    • Nausea
    • Vomiting
    • Diarrhoea
    • Mucosal ulcers
    • Skin reactions, including ulceration

Hydroxyurea is a mainstay of current CML treatment. It rapidly lowers WBC counts and can be given orally. Its use does not appear to affect the results of subsequent treatment with SCT or IFN-α. It is given in doses of 40 mg/kg daily and adjusted to maintain leukocyte counts in the range of 210 x 109/L.