In the current issue of Clinical Lymphoma and Myeloma are articles by Daniel Catovsky and Kanti Rai about the relative merits of chlorambucil and fludarabine. I won't go into Kanti's article except to quote this "We do not by any means suggest that chlorambucil as a therapeutic agent should be abandoned."
Daniel's article goes much further. He suggests that clinical trials using chlorambucil have been unfairly biased against it. (Why would that be, I wonder? Could it be that there is no money to be made from chlorambucil?)
He presents evidence to show that the dose of chlorambucil needs to be at least 70 mg/sq meter/month and that the duration of treatment needs to exceed 6 months, preferably up to 12 months. I have already written about this until I am blue in the face, but here is additional evidence that I have not previously mentioned.
I had often puzzled over the fact that the French version of CHOP did so much better than other versions. The answer is now clear: they used double the dose of alkylating agent (cyclophosphamide) and half the dose of anthracycline (doxorubicin) as other people. The Jaksic trial of 1997 had impressive overall response rates of 89.5%. He pushed chlorambucil to toxicity at a dose of between 150-180 mg/sq m/month.
Catovsky comments that the chlorambucil arm of the bendamustine trial was a real outlier, with a response rate of only 31% and a PFS of only 7 months. This compares with the CLL4 trial which had a response rate of 72% and a PFS of nearly 2 years. What he doesn't realise is that the dose of chlorambucil in this trial was calculated according to 'ideal weight'. How many of us (especially we older ones) are at our ideal weight. And if you delve into the small print you find that 'ideal weight' is a function of height. So the dose of chlorambucil in that trial was calculated according to the patient's height! Who ever heard of such a thing? I cannot believe that anything other than obfuscation was intended. And to show Bendamustine in a more favorable light.
Chlorambucil is considerably less toxic than fludarabine, even when given in full doses. My spies tell me that Bendamustine is a lot more toxic than it is claimed to be. There is still life in the old dog, yet.