The Leukemia & Lymphoma Research's CLL4 trial included 777 patients who were diagnosed with chronic lymphocytic leukemia (CLL) between 1999 and 2004. It was led by The Institute of Cancer Research (ICR) and provides the most comprehensive information on the patients' quality of life.
For five years after treatment was initiated, participants consistently reported the main indicators of their physical, social and emotional quality of life. The participants received either chemotherapy with fludarabine, the 'milder' chlorambucil, or the more toxic, yet more effective combination therapy of fludarabine and cyclophosphamide (FC).
FC in combination with rituximab, a monoclonal antibody drug, has proven to be the most effective therapy for extending life and has become the standard treatment for patients with CLL. Scientists were concerned that the FC-based treatment could have intolerable effects on the patients' quality of life, regardless of its benefits to extend survival.
However, the CLL4 trial managed to prove that although the effects of FC therapy on the patients' quality of life is more adverse for the first few months of therapy than other therapies, the quality of life in the long-term is nevertheless just as good. In fact, the quality of life for patients who had a long remission after therapy was comparable to that of the age and sex of the normal population.
Leading author Monica Else from The Institute of Cancer Research declared:
"This is the first concrete evidence that FC treatment does not impair quality of life over the long term. Because FC is effective at creating long term remission, free of any serious symptoms, patients reported benefits from not constantly relapsing and having to receive repeated treatment."
Emeritus Professor Daniel Catovsky, senior researcher from the ICR, added:
"The CLL4 clinical trial showed the benefits of FC for patients and is the basis for its use today, in combination with the drug rituximab, as the standard treatment of CLL. Additionally, it has helped doctors to customize treatment for each patient by establishing testing for different prognostic markers in CLL that can dictate how each individual's disease will respond to therapy."
Given that FC is more toxic as compared with chlorambucil or fludarabine alone patients reported greater levels of fatigue and more social exclusion in the first year of therapy, which could be due to the drug's immunosuppressive nature. The study revealed however, that patients on all therapies reported similar quality of life after the first year.
Scientific Director at Leukemia & Lymphoma Research, Dr David Grant, explained:
"CLL is predominantly a disease of the elderly, so side-effects that drugs can have on patients are a major concern, with more aggressive drugs causing nausea, fatigue and susceptibility to infection. CLL remains an incurable cancer but this study offers reassurance that powerful initial treatment can allow patients to enjoy a high quality of life for years in remission."
The researchers note that several patients who relapsed during the CLL4 trial after receiving chlorambucil switched treatment to FC given that the therapy's greater efficacy was already emerging. Chlorambucil is still administered, although mainly in the very elderly and weak patients who would have no tolerance for FC therapy.