The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Continuous Infusion High-Dose Leucovorin with 5-Fluorouracil and Cisplatin for Untreated Stage IV Carcinoma of the Head and Neck

Arnon I. Dreyfuss, MD; John R. Clark, MD; Joel E. Wright, PhD; Charles M. Norris Jr., MD; Paul M. Busse, MD, PhD; James W. Lucarini, MD; Barbara G. Fallon, MD; Donna Casey; Janet W. Andersen, MS; Richard Klein, BS; Andre Rosowsky, PhD; Daniel Miller, MD; and Emil Frei III, MD
[+] Article, Author, and Disclosure Information

Grant Support: Supported in part by grant P01-CA19589 from the National Institute for Health.

Request for Reprints: Arnon I. Dreyfuss, MD, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

Current Author Addresses: Drs. Dreyfuss, Clark, Wright, Rosowsky and Frei and Ms. Casey and Andersen: Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

Drs. Norris, Lucarini and Miller: 110 Francis Street, Boston, MA 02215. Dr. Busse: New England Deaconess Hospital, 185 Pilgrim Road, Boston, MA 02115.

Dr. Fallon: St. Francis Hospital Medical Center, 114 Woodland Street, Hartford, CT 06105.

Mr. Klein: New York Medical College, P.O. Box 111, Valhallah, NY 10595.

Ann Intern Med. 1990;112(3):167-172. doi:10.7326/0003-4819-112-3-167
Text Size: A A A

Study Objective: To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck.

Design: Nonrandomized, prospective trial.

Setting: A comprehensive cancer center.

Patients: Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity.

Interventions: Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/ m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy.

Results: A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (± SD) was 34.3 ± 1.5 μmol/L, of which only 8.0 ± 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 ± 0.6 ¼mol/L.

Conclusions: Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.





Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment
Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Related Articles
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.