Randomized phase I trial of recombinant human keratinocyte growth factor plus chemotherapy: potential role as mucosal protectant.

PURPOSE To evaluate the safety of recombinant human keratinocyte growth factor (KGF) when administered with fluorouracil (FU) in patients with metastatic colorectal cancer. PATIENTS AND METHODS Patients (N = 81) received KGF by intravenous (IV) bolus on days 1 to 3, followed by FU 425 mg/m2/d IV bolus plus leucovorin 20 mg/m2/d IV on days 4 to 8. KGF dose levels were 1, 10, 20, 40, 60, and 80 microg/kg/d. A randomized, placebo-controlled design was employed (2:1 randomization of KGF to placebo). Oral mucositis was assessed by examination on days 1, 4, 8, 15, and 28. In addition, patients provided daily assessments of oral symptoms using a self-administered questionnaire. RESULTS Skin and oral events occurred in 13 of 18 patients (eight patients, grade 1; four patients, grade 2; and one patient, grade 3) treated with 60 and 80 microg/kg of KGF and three of 11 patients treated with 40 microg/kg (grade 1). These symptoms were dose limiting in three cases (ie, in two of 10 patients treated with 80 microg/kg and in one of eight patients treated with 60 microg/kg). The frequency of grade 2 to 4 mucositis was 43% in patients treated with KGF, compared with 67% in patients treated with placebo (P =.06). Patient self-assessments of oral pain and clinical assessments of mucositis showed good correlation (Kendall's tau = 0.75). CONCLUSION KGF is generally well tolerated when administered IV at doses up to 40 microg/kg/d for 3 days before a 5-day course of FU plus leucovorin. A clinically meaningful biologic effect was also suggested in that patients treated with the epithelial growth factor KGF had a lower rate of grade 2 to 4 mucositis than did patients treated with placebo.