Chlorambucil again

[Miee]

Hi everyone,

I think it is generally believed that fludarabin monotherapy does not improve overall survival compared to classic therapy chlorambucil monotherapy. Then, does chlorambucil monotherapy improve overall survival compared to non-treated patients? I have not found such a clinical trials, but found an old scientific paper on the clinical trial of effects of chlorambucil monotherapy on 612 patients (CLL stage A) (Bood, Vol. 75, 1414-1421, 1990). Surprisingly this study showed that chlorambucil treated patients reduced overall survival. In this paper, authors described that ‘Chlorambucil has been the most common treatment in CLL for 30 years although its beneficial role has never been proved’. I think that these indicates that fludarabin monotherapy does not improve overall survival compared to non-treated patients.

I hear that now chlorambucil monotherapy is used for older patients, because it is mild drug. If overall survival is not extended by chlorambucil monotherapy, what is the benefit? Improve quality of life by a temporary remission?

Miee

[AussieNeil Administrator]

Miee, until FCR was trialled by M D Anderson, no treatment had been shown to extend survival time with CLL. There's now an expectation that the new small molecule non-chemo drugs will also be show to extend survival time when trial patients have been on them long enough. Also, for some people with the right CLL genome, FCR may even have cured them of CLL as some of the early trial patients are still going strong on watch and wait (again) after being on the early FCR trials some 12 or more years ago and have not required further treatment.

The reason for watch and wait before eventual treatment, is sadly because of what you've said in your final sentence - improved quality of life. Basically those that need treatment do so because the CLL is rapidly growing, is suppressing the bone marrow so the patient can't produce enough blood cells, nodes are becoming bulky and painful or pressing on vital organs and so on. With the older treatments, it's a trade off between clearing out the CLL so that bone marrow can again produce the needed quantity of blood cells and nodes and spleen are no longer enlarged versus the long term side effects of the treatment. These can be long term suppression of your immunity, secondary cancers (including other blood cancers), bone marrow failure (MDS) and the creation of more aggressive CLL clones, so treatment is generally required again soon with usually a shorter remission and more side effects and so on.

These are all good reasons to try and forget about treatment and stay in watch and wait as long as you can. Unfortunately, if you do get to the stage of needing treatment, you can't put it off too long, as you need a buffer in your body's ability to make needed blood cells as these take a hit during treatment - you need enough to survive treatment .

Neil