Neurotoxicity in a phase I trial of continuous-infusion cisplatin with hyperfractionated radiotherapy for locally advanced head and neck cancer

✍ Scribed by Gerald H. Clamon; Lynn Baatz; Henry T. Hoffman; David H. Hussey; Matthew Glascock; Timothy M. McCulloch; Scott M. Graham

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 569 KB
• Volume: 18
• Category: Article
• ISSN: 1043-3074
• DOI: 10.1002/(sici)1097-0347(199605/06)18:3<236::aid-hed5>3.0.co;2-0

✦ Synopsis

Background:

Both twice daily fractionated radiotherapy and concurrent cisplatin with once-daily radiotherapy have been shown to improve local disease control in patients with head and neck cancer. the objective of this phase i trial was to determine the maximum tolerated dose of cisplatin which could be given as a continuous infusion concurrent with twice-daily radiotherapy to patients with locally advanced head and neck cancer.

Methods:

Patients were treated with radiotherapy at doses of 110 cgy twice daily for 5 days per week to a total dose of 7040-7590 cgy. concurrent with radiotherapy, patients received continuous-infusion cisplatin for 5 days per week. groups of 3-6 patients were treated with doses of 1-3 mg/m2/day.

Results:

Central nervous system toxicity became dose-limiting. at 1 mg/m2, 2 mg/m2, and 3 mg/m2 confusion was observed and one patient had a seizure. at 3 mg/m2, another patient suffered severe sensory and motor neuropathy. despite bulky tumors, 12 of the 14 patients had an objective response and 3 achieved a complete response.

Conclusion:

The combination of twice-daily fractionated radiotherapy and concurrent cisplatin by continuous infusion is severely toxic and achieves results similar to less toxic programs. it is not recommended for further investigation or therapy.