Chemotherapy of myeloma: Drug combinations versus single agents, an overview, and comments on acute leukemia in myeloma
✍ Scribed by Daniel E. Bergsagel
- Publisher
- John Wiley and Sons
- Year
- 1988
- Tongue
- English
- Weight
- 499 KB
- Volume
- 6
- Category
- Article
- ISSN
- 0278-0232
No coin nor oath required. For personal study only.
✦ Synopsis
My role in this conference is to evaluate the proposition that drug combinations are more effective than melphalan and prednisone in the treatment of plasma cell myeloma. Drug combinations are generally accepted as being more effective than single agents in the treatment of many malignancies, but the application of this principle to myeloma is still controversial. In examining controversies such as this I have found that the easiest person to convince is myself, and I suspect that many others have a similar gullibility for their own convictions. This is one of the reasons why scientific journals need external referees for the articles submitted to them. It is important to detect gaps in logic and the self-deception that occurs when the hypothesis one is testing becomes confused with an established fact. This, I believe, has happened in the field of medical oncology. Many oncologists accept the hypothesis that combination chemotherapy is better than treatment with a single agent as an established fact. In the treatment of Hodgkin's disease it is true that many drug combinations appear to be better than single agents such as nitrogen mustard or vinblastine, but well-designed trials, using a dosage schedule for the single agent that is just as intense and prolonged as the drug combination, have not been done. Furthermore, it is a mistake to try to generalize this principle from Hodgkin's disease to all other malignancies. Drug combinations do not appear to be more effective than single agents in the treatment of some responsive malignancies such as chronic granulocytic leukemia and low-grade non-Hodgkin's lymphomas, and 1 am not convinced that the principle applies to plasma cell myeloma.
I belabour this point because it is such a mistake to confuse a hypothesis with an established fact, since, like a siren's song, it attracts uncritical, enthusiastic attention and diverts us from more useful approaches to investigating the problem.
In this talk I will evaluate nine prospective randomized trials, which have been reported within the past 10 years, comparing the effectiveness of melphalan and prednisone (MP) with various drug combinations in the treatment of plasma cell myeloma. In addition, I will report on the incidence of acute leukemia in myeloma patients receiving maintenance, or no maintenance therapy, in the National Cancer Institute of Canada's (NCI-C) MY2 protocol study (Belch et al., 1984).
The early studies of drug cornbinations grew out of the evidence that alkylating agents are not cross-resistant in the treatment of either mouse or human plasma cell tumours. We reasoned that there might be an advantage to combining alkylating agents. Several prospective studies have been done to test this hypothesis.