Phase III Trial of Amisfostine with Chemoradiation for Inoperable Non Small Cell Lung Cancer (NSCLC): Does Amifostine Protect Cancer Cells?

Reviewer: Ryan Smith, MD
OncoLink
Last Modified: October 8, 2002

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Presenter: Ritusko Komaki
Presenter's Affiliation: MD Anderson Cancer Center
Type of Session: Scientific

Background

    Several randomized studies have proven improved outcomes with chemoradiation vs. radiation alone in the treatment of inoperable NSCLC. More recently, there has been evidence that concurrent chemoradiation is more efficacious than sequential chemoradiation. However, with this concurrent treatment comes increased toxicity. The most notable is acute esophagitis, but there is also a small but real number of patients who will develop radiation pneumonitis. Amifostine is a radioprotector that has been hypothesized to prevent mucositis, esophagitis, and pneumonitis. This study reports on the use of amifostine in patients treated with chemoradiation.

Materials and Methods

  • 62 patients were enrolled (31 on each arm with well-balanced patient characteristics)
  • All had Stage II or III inoperable NSCLC, with KPS 70 or greater, without weight loss
  • All received concurrent chemoradiation consisting of 1.2 Gy BID to 69.6 Gy
  • Chemotherapy was cisplatin 50 mg/m2 d 1, 8, 29, 36 and oral etoposide 50mg BID x 10 d starting day 1 and day 29
  • Patients were randomized to either receive amifostine (500mg IV over 5 minutes prior to the PM radiation treatment) or no additional treatment
  • Minimum follow up was 12 months, with median follow up of 22 months

Results

  • Incidence of Grade 3 acute esophageal toxicity was 30% vs. 6% (p=.017) favoring the amifostine group. More patients in the amifostine group had mild esophageal toxicity, with an associated reduction in the moderate to severe toxicity.
  • Incidence of pneumonitis was 0 in the amifostine group, compared to 19% in the control group (p=.009)
  • Neutropenic fever was reduced in the amifostine group (40% vs. 16%)
  • Amifostine had more associated hypotension (3% vs. 65%), sneezing (0 vs. 13%), and nausea (10% vs. 32%)
  • Overall survival was unchanged between the two groups (1yr 77% vs. 71%, 2 yr 39% vs. 42%)
  • Median survival was unchanges between the two groups (20 months vs. 19 months)
  • There was no difference in local control, though the actual figures were not given

Author's Conclusions

  • Concurrent chemoradiation is effective in the treatment of inoperable NSCLC
  • Amifostine reduces esophagitis, pneumonitis, and neutropenia
  • Amifostine shows no evidence of tumor protection

Clinical/Scientific Implications

    Concurrent chemoradiation has become the standard of care for good KPS patients with inoperable NSCLC. However, this is associated with signficant normal tissue toxicity, with acute esophagitis rates exceeding 30% in reported studies. Amifostine is a radioprotector that has been postulated to decrease this toxicity. As shown in this study, it is successful in reducing esophagitis, pneumonitis, and neutropenic fever. However, with this short of follow up, figures on pneumonitis may change, as some patients develop pneumonitis as a later toxicity. Also, amifostine is not without toxicity itself. There is a high incidence of nausea and hypotension, not to mention rash and allergic reactions. Patients undergoing chemoradiation already have a high propensity to develop these toxicities. Therefore, whether amifostine is truly efficacious in this setting requires individual consideration of these factors. It should also be noted that these toxicities have patient subjectivity, and in a non-blinded study, this could cloud the results. Amifostine has been proven to be efficacious in head and neck radiation, mainly due to salivary gland protection and the reduction of mucositis. This study supports additional investigation of Amifostine in the area of lung cancer.

Oncolink's ASTRO Coverage made possible by an unrestricted Educational Grant from Ortho Biotech.


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