Systemic chemotherapy for the treatment of mycosis fungoides and Sézary syndrome

ABSTRACT:  The treatment of mycosis fungoides and Sézary syndrome is unique. The treatments of choice are highly stage‐and practitioner‐dependent. For early stage patients, treatment with palliative topical therapies is often adequate to yield excellent, high‐quality and durable responses. For the more advanced stages, systemic approaches are more appropriate, either alone or in combination, to palliate patients. There is still little convincing evidence from randomized trials that any single approach is favorable for improving survival. Many practitioners believe the disease can be controlled with the host immune system, but there again is little scientific support for this conclusion. It has been hypothesized that some of our therapies work through this mechanism, such as photopheresis and perhaps even psoralen and ultraviolet A. Unfortunately, even the use of biologic response modifiers, such as interferon and the interleukins, is not absolutely supportive of an active role for immune surveillance since these agents have been shown to have cytotoxic and differentiating effects. Because of the above, many practitioners have actively discouraged the use of chemotherapy because it may impair the host immune system; certainly, the purine analogs would fall into this category. However, there is little evidence supporting significant immune effects for other chemotherapeutics, and clearly, the responses seen would support their use in appropriate patients. As the present authors will detail in this paper, the advances in understanding cancer biology and mechanisms of resistance should, in the future, lead to optimal selection of agents that are predicted to be optimally active, limiting the toxicity and waste associated with ineffective drug usage.