Phase III trial of cisplatin (P) plus etoposide (E) plus concurrent chest radiation (XRT) with or without consolidation docetaxel (D) in patients with inoperable stage III non-small cell lung cancer (NSCLC): HOG LUN 01-24/USO-023.
Reviewer: Christine Hill, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 2, 2007
Presenter: Hanna, N.H. Presenter's Affiliation: Indiana University, Indianapolis, IN Type of Session: Scientific
Concurrent platinum-based chemotherapy and thoracic radiation treatment (RT) has become a standard of care in the treatment of unresectable non-small cell lung cancer (NSCLC). This treatment methodology is based on studies published in the 1980's that demonstrated a survival benefit in NSCLC with the addition of sequential chemotherapy to RT alone, and further studies from the 1990's demonstrating a 3-4 month improved median survival time with the use of chemotherapy and RT concurrently.
Median survival with platinum-based chemotherapy and concurrent thoracic RT has been demonstrated to be 15-17 months by several groups, including the Southwest Oncology Group (SWOG) in their study 9410.
A further SWOG study, 9504, examined the addition of docetaxel maintenance chemotherapy following concurrent cisplatin, etoposide, and thoracic RT for patients with locally advanced NSCLC. SWOG 9504 was a single-arm, phase II study, which demonstrated a median survival time of 26 months. Since the publication of this data, taxane-based consolidation chemotherapy has become widely used in treatment of unresectable NSCLC following concurrent chemotherapy and RT.
This phase III trial was carried out to evaluate outcomes with the addition of docetaxel maintenance treatment to concurrent cisplatin, etoposide, and thoracic RT.
Materials and Methods
This phase III clinical trial was designed to enroll 259 patients, with planned randomization of 180, to demonstrate an improvement in median survival time (MST) from 15 months to 25 months with 80% power.
Inclusionary criteria included stage IIIA or IIIB NSCLC deemed unresectable, ECOG performance status 0-1 at time of enrollment (0-2 at time of randomization), FEV1 > 1L, and <5% weight loss.
All patients were treated with cisplatin, 50 mg/ m2, on days 1, 8, 29, 36, and etoposide, 50 mg/m2, on days 1-5 and 29-33. Concurrent with chemotherapy, patients received thoracic RT to a total dose of 5940 centigray.
Patients without progressive disease were then randomized to docetaxel maintenance treatment (75 mg/m2 every 3 weeks for 3 doses) versus observation.
This study was terminated early, after accrual of 203 patients and randomization of 147, due to evidence of futility on analysis of preliminary data.
Median follow-up time was 25.6 months.
Of the 203 patients accrued, 147 completed concurrent chemotherapy and RT and were randomized.
Of these, 83% of patients randomized to receive docetaxel maintenance received all 3 planned docetaxel cycles.
MST for all patients enrolled was 21.2 months. MST was 24.1 months for the observation arm versus 21.5 months for the docetaxel arm (p = 0.941)
Progression free survival (PFS) for the observation arms was 12.9 months versus 12.3 months in the docetaxel arm (p = 0.942).
Three-year overall survival (OS) was 28% in the observation group versus 27% in the docetaxel group (p = 0.9).
Incidence of grade 3-4 infection was 8.9% for the whole group during concurrent chemoradiation treatment,11% in the docetaxel arm, and 0% in the observation arm. Incidence of treatment-related death was 1.5% during concurrent chemoradiation, 5.5% during docetaxel maintenance, and 0% during observation.
28.8% of patients randomized to docetaxel maintenance were hospitalized during their treatment versus 8.1% of patients randomized to observation.
MST in both arms of this trial was higher than has been historically described
Consolidation docetaxel did not improve MST, PFS, or 3-year OS.
Consolidation docetaxel was associated with increased risk of grade 3-4 infection, hospitalization, and treatment-related death.
This trial showed an improvement in MST, PFS, and 3-year OS when compared to historical controls. Improved patient selection with increased availability of PET and MRI scan may contribute to this by allowing elimination of patients with occult stage IV disease from the trial. Still, MST and OS were moderately reduced in this study when compared to the SWOG 9504 phase II trial. The authors note that this may be due to more rigorous requirements for pulmonary function in SWOG 9504 versus this trial (FEV1 > 2 L versus FEV 1 ≥ 1 L, respectively).
This trial showed no overall survival benefit with the addition of docetaxel maintenance to concurrent chemoradiation. Given the significant increase in toxicity described in this study, maintenance taxol-based chemotherapy should likely not be used for patients with unresectable stage III NSCLC after definitive, concurrent, platinum-based chemoradiation outside of a clinical trial.
Dec 21, 2010 - An acne-like rash among patients with non-small-cell lung cancer undergoing treatment with cisplatin and vinorelbine plus cetuximab is associated with improved outcomes, according to research published online Dec. 20 in The Lancet Oncology.