Presenter: R. Komaki Affiliation: Radiation Oncology, University of Texas M. D. Anderson Cancer Center,
The radioprotective property of thiol-containing compounds has been
well known for some time. Amifostine(WR-2721) is the most well known of
these agents. The proposed mechanism of action is the scavenging of
radiation-induced free radicals.
A prospective randomized study was conducted to determine
whether amifostine reduces the rate of severe esophagitis, hematologic, and
pulmonary toxicities associated with concurrent chemoradiation and/or
improves the survival of patients with inoperable NSCLC.
Materials and Methods
62 patients with inoperable stage II or III NSCLC were entered onto this
single institution randomized study.
They were treated by thoracic radiation therapy (TRT) with 1.2 Gy/Fx,
bid to a total dose of 69.6 Gy and oral VP-16 and cisplatin
Amifostine (500 mg i.v. twice weekly) was given before chemoradiation
(Arm 1); the control group received chemoradiation without amifostine (Arm
Thirty-one patients were enrolled in each arm with a median follow-up
of 6 months.
Patient and tumor characteristics were equally distributed in both
Complete response (CR) occurred in 11 of the 31 patients who received
amifostine (35%) and in 6 of the 31 patients (19%) who did not (p=
Median survival time has not yet been reached on arm 1; it was 20
months on arm 2.
Severe acute esophagitis ( grade 3) was 6.5% in Arm 1
compared to 26%in Arm 2 (p=0.038).
Acute pneumonitis ( grade 3) was 3.2% in Arm 1 compared to 19%
in Arm 2 (p = 0.045).
There was no significant difference in hematologic toxicities between
the two arms. Hypotension (20 mm Hg decrease from baseline BP) was
significantly more frequent in Arm 1 65% vs 3.0% in Arm 2 (p=0.00001).
Only one patient discontinued the treatment because of a hypotensive
Amifostine significantly reduced acute pneumonitis and severe acute
esophagitis although it caused significantly more hypotensive episodes.
Further follow-up is needed to evaluate the long-term effects in late
reacting normal tissues as well as survival.
One of major implications of this study is that more rigorous cancer
regimens, such as those utilizing chemoirradiation, might be employed if
integrity of normal tissue could be preserved.
Of course, when discussing radioprotectants, one must always be aware
of the theoretical concern of tumor protection.
Another interesting area of active research is the use of subcutaneous
amifostine, which offers a more convenient method of delivery than the
i.v. form, and may have a better side-effect profile.
Nov 27, 2014 - In a phase III clinical trial, gefitinib was superior to carboplatin-paclitaxel in extending survival for patients with non-small-cell lung cancer, particularly those patients with epidermal growth factor receptor gene mutations, according to a study published online Aug. 19 in the New England Journal of Medicine.