By Chris Berrie
BERLIN -- September 28, 2009 -- Continuous hyperfractionated accelerated radiotherapy (CHART) fractionation after neoadjuvant chemotherapy is a promising option for treatment intensification in patients with locally advanced non-small-cell lung cancer (NSCLC).
Michael Baumann, MD, PhD, Cancer Centre, Klinik and Poliklinik Strahlentherapie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany, presented the findings of a randomised, active-comparator, phase 3 study at the joint 15th Congress of the European Cancer Organisation (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO).
Standard RT for control of inoperable NSCLC involves 60 Gy exposure. In the CHART study, this was compared to 54 Gy over a more intense 12-day regimen. This produced a 10% benefit for overall survival (OS) despite more severe early reactions, according to Dr. Baumann. "The improvement in CHART was caused by better local control," he said on September 23.
The CHARTWEL (CHART Weekend Less) study was based on the hypothesis that accelerated RT counteracts the repopulation of tumour cells during treatment, which might be achieved not by RT dose escalation, but by accelerated RT.
A total of 406 patients with NSCLC were stratified according to centre, stage, histology, and neoadjuvant chemotherapy.
Patients were randomised to conventional fractionation of 66 Gy as 2 Gy/day (excluding weekends) over 6.5 weeks (CF; n = 203), or to CHARTWEL fractionation of 60 Gy as 3x 1.5 Gy/day (excluding weekends) over 2.5 weeks (CW; n = 203). Patient baseline characteristics were similar between groups.
The primary endpoint was OS, with secondary endpoints of time to progression, time to distant metastases, disease-free survival (DFS), side effects, and failure pattern.
There were no significant differences for OS up to 5 years for patients in the CF group, compared with patients in the CW group (11% vs 7%; P = .43), as seen for DFS (P = .49), local tumour control (P = .22), and distant-metastases-free survival (P = .71).
However, Dr. Baumann noted that with this decrease in RT (CF, 66 Gy; CW, 60 Gy), there was no loss of locoregional tumour control, while local regional failure was the leading cause of death. Furthermore, the CW regimen was shorter than CF, demonstrating involvement of a time factor in this RT treatment.
Exploratory analyses for locoregional tumour control indicated significant benefit for CW over CF (P = .019) for patients receiving chemotherapy (n = 106), over those who did not (n = 300). This was accompanied by significant improvements with CW for locoregional tumour control according to increasing tumour N stage (P = .0245), T stage (P = .0158), and International Union Against Cancer (UICC) stage (P = .0060).
For side effects, dysphagia grade >=2 was seen earlier and more frequently with CW over CF; however, these conditions soon settled. Of particular note, late damage associated with these treatment regimens was not increased by CW treatment, over CF.
"From these data, we draw the overall hypothesis that CHARTWEL after neoadjuvant chemotherapy is a promising avenue to intensify treatment in locally advanced non-small-cell lung cancer," concluded Dr. Baumann.
[Presentation title: Final Results of CHARTWEL (ARO 97-1): Hyperfractionated-Accelerated vs Conventionally Fractionated Radiotherapy in Non-Small-Cell Lung Cancer (NSCLC). Abstract 4LBA]
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