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


CONCLUSIONS
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.
Clamon
G H
GH
University of Iowa Hospitals and Clinics, Department of Internal Medicine, Iowa City, USA.
Baatz
L
L
Hoffman
H T
HT
Hussey
D H
DH
Glascock
M
M
McCulloch
T M
TM
Graham
S M
SM
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002493:Central Nervous System Diseases / Q000139:chemically induced*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D015996:Survival Rate; D016896:Treatment Outcome
D011838:Radiation-Sensitizing Agents; D002945:Cisplatin