Journal of Clinical Oncology, Vol 6, 618-626, Copyright © 1988 by American Society of Clinical Oncology
Cisplatin, fluorouracil, and high-dose leucovorin for recurrent or metastatic head and neck cancer
EE Vokes, KE Choi, RL Schilsky, WJ Moran, CM Guarnieri, RR Weichselbaum and WR Panje
Department of Medicine, University of Chicago, IL.
We added high-dose oral leucovorin to the combination of cisplatin and
fluorouracil (5-FU) to assess the efficacy of this regimen in the treatment
of patients with head and neck cancer. Cisplatin, 100 mg/m2, was followed
by a 5-FU continuous infusion at 600 mg/m2/d for five days. Leucovorin, 50
mg/m2, was administered at the start of cisplatin and every six hours
throughout the duration of the 5-FU infusion. The dose of 5-FU was
escalated to 800 mg/m2 and 1,000 mg/m2 according to observed toxicity. In a
second phase of the study, the dose of leucovorin was escalated to 50 mg/m2
every four hours. A total of 25 patients were registered: 23 had recurrent
disease after extensive prior treatment; and two had newly diagnosed
metastatic disease. The maximally tolerated dose of 5-FU was 800 mg/m2/d
with leucovorin administered every six hours. Toxicities at that level
included mild to moderate myelosuppression and dose-limiting mucositis in
the previously irradiated field. Identical toxicities were observed when
administering 800 mg/m2/d of 5-FU with leucovorin every four hours.
Eighteen patients were evaluated for response: one had a pathologic
complete response; nine had a partial response (including four who received
prior cisplatin and 5-FU as induction chemotherapy); and eight patients
failed to respond. The mean peak and trough plasma leucovorin
concentrations were 2.61 (+/- 1.07) mumol/L and 2.46 (+/- 0.95) mumol/L
with administration of the drug every six hours, and 2.75 (+/- 2.15)
mumol/L and 2.52 (+/- 1.48) mumol/L with administration every four hours.
We conclude that the combination of cisplatin, 5-FU, and leucovorin has
activity in the treatment of recurrent head and neck cancer. The maximally
tolerated dose of 5-FU in this study was 800 mg/m2/d, with mucositis in
previously irradiated sites being dose- limiting. Plasma leucovorin
concentrations exceeding 1 mumol/L are achieved following oral
administration of this drug.
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