Recombinant Human Keratinocyte Growth Factor (RHUKGF) Prevents Chemotherapy-Induced Mucositis In Patients With Advanced Colorectal Cancer: A Randomized Phase II Trial

Heather Jones, MD

University of Pennsylvania Cancer
Last Modified: May 14, 2001

Presenter: Stephen John Clarke
Affiliation: Royal Prince Alfred Hospital, Camperdown, Australia


    Oral mucositis in cancer patients receiving chemotherapy can lead to dose reduction and/or treatment breaks, both of which could have a negative impact on treatment outcomes. The use of 5-fluorouracil (5-FU) and folinic acid for the treatment of advanced colon cancer is associated with a 70% oral mucositis rate overall and a 20 to 30 % severe mucositis rate. Recombinant HuKGF is an epithelial specific growth factor. A previously reported phase I clinical trial in patients with advanced colorectal cancer demonstrated that rHuKGF reduced the incidence of oral mucositis caused by chemotherapy as compared to placebo (43% and 67% respectively; p=0.06). To establish the efficacy of the agent this randomized phase II trial was carried out.

Materials and Methods:

  • Sixty-four patients with advanced colorectal cancer were enrolled on to the trial, 42 males and 22 females
  • Median age 65 (range 37-88)
  • Median ECOG performance status of 1(range 0-2)].
  • Patients were randomly assigned to receive 2 cycles of either rHuKGF 40 [Micro]g/kg/day or placebo by IV bolus on days 1-3, followed by bolus 5-FU 425 mg/m2/day plus leucovorin 20 mg/m2/day on days 4-8 of a 28 day cycle.
  • Oral cryotherapy was not permitted in this trial.


  • The incidence of Grade 2, 3, and 4 mucositis in two cycles combined was 78% in the placebo (n=36) and 32% in the rHuKGF group (n=28) [p=0.001].
  • A significant reduction in the duration of mucositis was also observed (10.2 days for placebo and 3.4 days for rHuKGF; p=0.001).
  • Recombinant HuKGF had no effect on median survival
  • The most common treatment-related adverse events were mild to moderate skin-related events including rash, flushing, and edema
  • Asymptomatic and reversible increases in amylase and lipase were observed after rHuKGF administration.

Authors' Conclusions

  • These results confirm and extend previous clinical observations of the efficacy and safety profile of rHuKGF.
  • Recombinant HuKGF is able to reduce the incidence, severity and duration of chemotherapy-induced mucositis.

Clinical/Scientific Implications:

    This was a well-done study demonstrating the protective efficacy of this agent. Treating advanced malignancies often calls for aggressive therapy to get a positive out come. Often patients due to gastrointestinal mucositis are placed on a treatment break or have a reduction in the intensity of their treatment. Both actions can influence the treatment outcome. Having a protective agent, as rHuKGF helps reduce the likelihood of dose reduction and/or treatment delays. We look forward to the results of rHuKGF used in chemoradiation trials for head and neck cancer patients.

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