NEW YORKAn improved 2-year survival rate was achieved in stage
III non-small-cell lung cancer (NSCLC) patients with a combination of
paclitaxel (Taxol) and carboplatin (Paraplatin) given concurrently
with radiation therapy, according to a report at the Chemotherapy
Foundation Symposium XVII.
The median 1-year survival for the two-drug regimen plus radiation
therapy was about the same as when only paclitaxel was used with
radiation therapy (20.5 vs 20 months), said Hak Choy, MD, professor
of radiation oncology, Vanderbilt University Medical Center.
The separation of survival comes at the 2-year point, he
said. When only paclitaxel was used with radiation therapy, survival
was 33%. With both drugs and radiation therapy, it was 43%.
In the single-drug phase II trial of 33 patients, paclitaxel was
infused at 60 mg/m²/wk for 6 weeks concomitantly with radiation.
In the phase II trial of the dual-drug regimen, involving 39
patients, both drugs were given weekly for 7 weeks, paclitaxel at 50
mg/m² (1-hour infusion) and carboplatin (AUC 2) along with
radiation to a total of 66 Gy. Two cycles of paclitaxel at 200 mg/m²
and carboplatin (AUC 6) were then administered at 3-week intervals.
In a third phase II study, the same dosage schedule was used for the
two drugs, but a hyperfractionated radiation schedule was used: 1.2
Gy twice a day to a total of 69.6 Gy. Median survival has not yet
been established in this trial, Dr. Choy noted.
What we are learning from phase II studies, Dr. Choy said
in an interview, is that median survival is much better than
what we saw from radiation alone or from a platinum-radiation
combination. But we are still at the phase II stage, and there is yet
to be a phase III trial completed to make this a standard
recommendation. Use of a taxane-radiation combination, he
added, is feasible in community hospitals.
The 10% gain in survival achieved by adding carboplatin to the
regimen, Dr. Choy said, came at a cost of increasing the
esophagitis rate from 7% to 25%. If we have a healthy,
good-performance patient, I think the 18% increased toxicity may not
be that big an issue, since we are gaining 10% survival time.
However, if we have an elderly, poor-performance patient, that may
become a big issue. So patient selection is going to play a major
role in deciding whether you should use one drug or two drugs with radiation.
He noted that other studies are using amifostine (Ethyol) to reduce
the incidence of esophagitis .
To try to determine the optimal sequence of therapy, Dr. Choy and his
colleagues have launched a new study with the acronym LAMP (Locally
Advanced Multimodality Protocol).
So far, 70 patients have been randomized to the three different arms:
(1) paclitaxel-carboplatin induction followed by radiation alone; (2)
paclitaxel-carboplatin induction followed by radiation and concurrent
weekly paclitaxel-carboplatin infusions; and (3) radiation therapy
with weekly paclitaxel-carboplatin followed by chemotherapy with the
drug combination. When this trial is finished, well
probably go to phase III studies based on the best arm, he said.
Dr. Choy is also conducting a trial of paclitaxel-radiation in
poor-prognosis patients. Those patients would typically get
radiation alone. In this trial, were going to be giving
paclitaxel weekly for 6 weeks and give split-course radiation,