8-A842A-2018-Multiple-00021-Chapter 29-ROUND-2

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Section II Techniques, Modalities, and Modifiers in Radiation Oncology

H and E

Masson’s Trichrome

Vehicle

RT + Vehicle

RT + KGF5

Figure 29.4.  Mitigation of radiation-induced fibrosis attributable to single dose of recombinant human keratinocyte growth factor (KGF) admin- istered after a course of fractionated hemithorax irradiation. The hematoxylin and eosin slides show the morphologic changes in the alveoli induced by irradiation including the inflamma- tory infiltrate and alveolar wall thickening. The Masson’s trichrome panels show the collagen deposition that is characteristic of fibrosis. KGF was given either at 5 mg/kg or 15 mg/kg. Less injury is seen with the higher dose of KGF, sug- gesting that a dose–response effect exists.

RT + KGF15

starting CRT and once weekly for 7 weeks. The incidence of severe oral mucositis, the primary end point, was significantly lower in the palifermin arm compared to placebo (54% vs. 69%; P = .041). Both overall survival and progression-free sur- vival were similar as well. However, no statistically significant differences emerged in secondary efficacy end points such as narcotic doses and duration of treatment breaks. A similar randomized phase III study examined palifermin at 120 mcg/kg in 186 head and neck cancer patients treated with postopera- tive CRT. 108 Palifermin again reduced the time to development and duration of WHO grade 3 or 4 oral mucositis without dif- ferences in patient-reported pain scores, treatment breaks, or efficacy. The precise role for palifermin in the management of head and neck cancer remains to be established. Treatment Radioprotectors and radiation mitigators are both designed to minimize the risk of clonogenic death of normal cells and sub- sequent disruption of the protective mucosal barrier. Head and neck RT also initiates a local cytokine cascade, which includes interleukin-1 and -6 and tumor necrosis factor- α (TNF- α ). An inflammatory response results, which contributes to the ulti- mate anatomic disruption of the mucosa. Secondary bacterial

A phase II study examined the safety and efficacy of palifer- min in locally advanced head and neck cancer patients. 106 Patients were randomized 2 to 1 between palifermin and pla- cebo. Palifermin was delivered at a dose of 60 mcg/kg. Institutions had the discretion to deliver RT via conventional once-daily 2-Gy fractions or with an accelerated hyperfraction- ated regimen of 1.25 Gy twice daily. One hundred patients were enrolled, of whom 34 received accelerated hyperfractionation and the remainder received standard fractionation. The first dose was delivered prior to the initiation of CRT and then every Friday afternoon after the last fraction of radiation. Two addi- tional doses of palifermin were given 1 and 2 weeks after the completion of RT for a total of 10 doses of the drug. Palifermin did not reduce the incidence or duration of mucosal or salivary gland toxicity. The subset of patients receiving hyperfraction- ated radiation, however, showed significant improvements in the duration and severity of mucositis (Fig. 29.5). They also had improved swallowing function and less salivary gland toxicity relative to patients who received placebo. A subsequent randomized phase III study examined a higher dose of palifermin at 180 mcg/kg to reduce oral mucosi- tis in 188 patients with locally advanced head and neck cancer treated with CRT. 107 Palifermin was administered prior to