Concurrent combined therapy

Problems are avoided by delivering chemotherapy and radiotherapy together. This approach has advantages and some disadvantages (see Table 9.2).

Ideally, cytotoxics chosen for chemo-irradiation regimens will have known activity against the tumour but will not have toxicities that overlap the effects of irradiation of the relevant region. Anthracyclines are avoided because of their effects on skin and mucosa; methotrexate can increase the damage to the normal lung following radiotherapy. Agents such as cisplatin and 5-fluorouracil are particularly attractive

Table 9.2 Benefits and problems of concurrent combined therapy

Advantage

Disadvantage

No delay in either therapy

Increased toxicity

Additive cell kill by two therapies

Compromised dose of one or both

treatments

Enhanced cell kill by radiosensitizing

Large volume irradiated

effects of chemotherapy

Reduced likelihood of evolution of

Pharmacodynamic interactions

resistance to either therapy

(e.g. cell-cycle effects)

because of their radiosensitizing effects. At least, in vitro, the interactions of chemotherapy and radiotherapy are complex and schedule-dependent: e.g. irradiation of cells may lead to cell-cycle arrest and this may confer relative resistance to subsequent exposure to phase-specific cytotoxics such as taxanes; conversely, exposure to taxanes can lead to radiosensitization.

An attempt must be made to minimize the normal tissue damage of radiation during combined therapy. Treatment times are often a minimum of 6 weeks (to reduce early normal reactions) and the dose per fraction is 2 Gy or less (to reduce late damage).

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