A Phase I/II Trial of Escalating Doses of Recombinant Human Keratinocyte Growth Factor (rHuKGF) in Head & Neck Cancer (HNC) Patients Receiving Radiotherapy (RT) with Concurrent Chemotherapy (CCT)

William Levin, MD
University of Pennsylvania Cancer Center
Last Modified: November 5, 2001

Presenter: D.M. Brizel
Presenter's Affiliation: Duke University
Type of Session: Scientific

Evidence from recent studies suggest that the combination of chemotherapy and radiation therapy improves outcome in advanced head and neck cancers, compared to single modality therapy. But these aggressive therapies frequently cause increases in treatment-related morbidity. Recombinant Human Keratinocyte Growth Factor (rHuKGF)stimulates the proliferation of epithelial tissues including the mucosa of the aerodigestive tract. Preclinical studies have shown that rHuKGF reduces the severity of RT and CT induced mucositis.

Materials and Methods

  • 60 patients with non-metastatic, previously untreated, stage 3 or 4 squamous cell HNC received hyperfractionated RT (1.25 Gy bid to a total dose of 72.5 Gy over < 7 weeks) and continuous infusion 5-FU (1000 mg/m2 /day for 4 days) and bolus cisplatin (100 mg/m2 during weeks 1 and 5).
  • A planned break in RT occurred at week 4.
  • Patients underwent randomization to receive intravenous rHuKGF (20, 40, 60, 80 ug/kg) or placebo, respectively, for 3 days immediately prior to the initiation of RT/CT, and then weekly for a total of 10 doses.
  • There was no stratification for T stage, N stage, performance status, or disease site.
  • Study endpoints included KGF-associated toxicity and the incidence and duration of severe mucositis (RTOG grade >= 3 ), acute pharyngitis and salivary gland toxicity (RTOG grade >= 2).
  • About half of the patients had cancer of the oropharynx.
  • 75% of patients had stage IV disease.


  • The only adverse effects attributable to KGF were skin flushing in 15% of patients and excess salivation in 2%.
  • Transient, asymptomatic elevations in serum lipase and amylase were observed at all KGF dose levels with three consecutive days of dosing.
  • Mucositis, dysphagia and xerostomia were significantly reduced in the rHuKGF Group.
  • There were no significant differences in 1-year actuarial local-regional control, failure-free survival, & survival for placebo and KGF patients.
  • Overall survival was about 70% at 2 years for both groups.

    Author's Conclusions

  • KGF was well tolerated at the dose levels in this study.
  • A larger scale phase II study is required to better evaluate the efficacy of rHuKGF.

    Clinical/Scientific Implications

  • The addition of KGF may allow for more aggressive regimens in the treatment of advanced head and neck cancers. At this time, there is no evidence that KGF stimulates proliferation of tumor cells, as evidenced by the survival data in this study.

    Oncolink's ASTRO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology and Pharmacia Oncology.