Journal of Clinical Oncology, Vol 21, Issue 8
(April), 2003: 1452-1458
© 2003 American Society for Clinical Oncology
Randomized Phase I Trial of Recombinant Human Keratinocyte Growth Factor Plus Chemotherapy: Potential Role as Mucosal Protectant
Neal J. Meropol,
Robert A. Somer,
John Gutheil,
Robert J. Pelley,
Manuel R. Modiano,
Eric K. Rowinsky,
Mace L. Rothenberg,
Spencer W. Redding,
Cuneyt M. Serdar,
Bin Yao,
Robert Heard,
Lee S. Rosen
From the Fox Chase Cancer Center, Philadelphia, PA; Sidney Kimmel Cancer Center, San Diego; Amgen Inc, Thousand Oaks; and Jonsson Cancer Center, University of California at Los Angeles, Los Angeles, CA; Cleveland Clinic Foundation, Cleveland, OH; Arizona Clinical Research Center, Tucson, AZ; Cancer Therapy and Research Center Institute for Drug Development, San Antonio, TX; and Vanderbilt-Ingram Cancer Center, Nashville, TN.
Address reprint requests to Neal J. Meropol, MD, Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia, PA 19111; email: nj_meropol{at}fccc.edu.
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 µg/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 µg/kg of KGF and three of 11 patients treated with 40 µg/kg (grade 1). These symptoms were dose limiting in three cases (ie, in two of 10 patients treated with 80 µg/kg and in one of eight patients treated with 60 µg/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 µg/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.
Supported by a grant from Amgen, Inc.
Presented in part at the Nineteenth Annual Meeting of the American Society of Clinical Oncology, May 20–23, 2000, New Orleans, LA.
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