A randomized study of concomitant radiotherapy with cisplatin or carboplatin versus radiotherapy alone in patients with locally advanced non-nasopharygeal head and neck cancer. A Hellenic Cooperative Oncology Group (HeCOG) phase III study

Reviewer: S. Jack Wei, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 1, 2003

Presenter: G Fountzilas
Presenter's Affiliation: Hellenic Cooperative Oncology Group
Type of Session: Scientific

Background

The prognosis of locally advanced head and neck cancer (HNC) is poor. More than 50% of patients with locally advanced HNC will recur locally despite optimal treatment and another 15-20% will develop distant metastatic disease. Several randomized trials have shown the superiority of combined modality treatment (CMT) over radiation therapy (RT) alone for overall survival (OS) and local control (LC); however, the optimal treatment regimen is still unclear. Platinum-based chemotherapy has been shown to be a radiation sensitizer. This study examines the benefit of a CMT regimen employing 2 platinum-based chemotherapy regimens versus RT alone.

Materials and Methods

124 patients with advanced non-nasopharyngeal HNC were enrolled between 1/95 and 7/99. The majority of patients had oropharyngeal or hypopharyngeal cancers.
Patients were randomized to 1 of 3 arms: 1) RT alone (70 Gy to gross tumor volume) or 2) The same RT with concurrent cisplatin (100 mg/m2 on days 2,22,42) or 3) The same RT with concurrent carboplatin (AUC 7 on days 2,22,42)
The majority of patients were stage IV
Patients were well-balanced between groups with regards to age, sex, race, performance status, and stage

Results

The combined modality arms were superior to RT alone with regards to 3-yr overall survival (OS) of 17.5% vs. 52% vs. 42% (p<0.001) (Arm 1, 2, and 3 respectively)
median survival was 12.2 mo vs. 48.6 mo vs. 24.5 mo, p=0.0003), and median time to progression (TTP) was 6.3 mo vs. 45.2 mo vs. 17.7 mo, p=0.0002).
No statistically significant difference was seen for complete response rate (27% vs 44% vs 42%, p=NS)
Overall, ~50% patients experienced moderate to severe toxicities in the CMT groups.
On multivariate analysis, smoking history, performance status, tumor grade, gender, primary site, and baseline tumor volume were independent prognostic factors for outcome

Author's Conclusions

CMT with platinum-based chemotherapy is superior for overall survival, median survival, and time to progression compared to RT alone.
Although bolus carboplatin appears to be inferior to bolus cisplatin as part of CMT in this study, statistical analysis cannot be performed between these 2 groups due to inadequate patient size.
The toxicities of these 2 CMT regimens appears to be tolerable, although alternative regimens should be investigated

Clinical/Scientific Implications

The findings of this study confirm previous results showing the benefit of CMT over RT alone for locally advanced HNC. Given the multiple randomized trials showing this result, CMT should be persued in all patients with locally advanced HNC who can tolerate this treatment. The question of which platinum-based regimen is superior is still open and future studies should address this important issue. However, at this time, cisplatin based regimens should be considered standard of care while carboplatin regimens are evaluated in clinical trials.

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