ORLANDO, FloridaAlthough a combination of paclitaxel,
carboplatin (Paraplatin), and thoracic radiation therapy is commonly used to
treat patients with locally advanced non-small-cell lung cancer (NSCLC), the
optimal sequencing of these therapies has not been defined. A multicenter phase
II trial explored this issue, and Hak Choy, MD, professor and vice chairman of
the department of radiation oncology at Vanderbilt University School of
Medicine, Nashville, presented the results (ASCO abstract 1160).
"We designed a trial to compare survival outcomes of three
taxane-based combined modalities," Dr. Choy said. The trial would also
investigate the safety and toxicity of the regimens and compare them to
Radiation Therapy Oncology Group (RTOG) reference survival data for sequential
chemoradiation, which is associated with a median survival time of 14.5 months.
The investigators enrolled 276 patients with unresectable stage
IIIA and IIIB NSCLC, Karnofsky performance scores ranging from 70 to 100, and
weight loss up to 10%. To be eligible, they could not have had prior
chemotherapy, radiation, or surgical resection.
Three Study Arms
Patients in the first cohort, the "sequential" arm,
received two cycles of paclitaxel, 200 mg/m², with carboplatin, AUC of 6,
followed by daily thoracic radiotherapy, 63.0 Gy. Patients in the second arm,
the "induction followed by concurrent" arm, started off with the same
two cycles of chemotherapy followed by 7 weeks of paclitaxel, 45 mg/m²/wk and
carboplatin, AUC of 2 weekly, with concurrent thoracic radiotherapy. The third
group, the "concurrent/consolidation" arm, was given radiation with
paclitaxel, 45 mg/m², and carboplatin, AUC of 2, followed by two cycles of
paclitaxel, 200 mg/m², and carboplatin, AUC of 6.
By November 2000, with 243 enrolled patients, investigators had
determined that the best survival was seen in arms 1 and 3. They enrolled an
additional 33 patients into these two arms by June 2001. Pretreatment
characteristics were balanced in terms of age, sex, Karnofsky scores, and
percent of weight loss, as well as histology and stage.
Toxicity and Survival
The most common toxicity during induction chemotherapy was
granulocytopenia, which was observed in about one-third of the patients in arms
1 and 2. During radiation therapy, esophagitis occurred in 3% of the patients
in arm 1, 19% in arm 2, and 28% in arm 3. Even with the esophagitis, 70% of
patients in arm 3 completed all 7 weeks of treatment, and 75% received two full
cycles of consolidation chemotherapy as planned.
The survival data for arms 1 and 2 were nearly identical to the
historical data. Arm 3, the concurrent/consolidation arm, demonstrated the best
outcome, showing a slight improvement in median survival time at 16.1 months.
The median survival in patients with a less than 5% weight loss increased to
17.2 months in arm 3.
"The survival in arm 3 appears to compare most favorably
with the RTOG control cohort," Dr. Choy said. "The toxicity was
acceptable in all three arms."