NEW YORKAn improved 2-year survival rate was achieved in stage III non-small-cell lung cancer (NSCLC) patients with a combination of paclitaxel(Drug information on paclitaxel) (Taxol) and carboplatin(Drug information on 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(Drug information on 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, he said.