Skip Navigation

This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Huinink, D. t. B.
Right arrow Articles by Keizer, H. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huinink, D. t. B.
Right arrow Articles by Keizer, H. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Annals of Oncology 12:357-363, 2001
© 2001 European Society for Medical Oncology

research-article

A phase I study of a fixed dose of cisplatin with increasing doses of raltitrexed (Tomudexreg;) in the treatment of patients with locally advanced or metastatic squamous cell carcinoma of the head and neck

D. ten Bokkel Huinink1,, M. E. T. Tesselaar1, R. J. Baatenburg de Jong2, H. P. Verschuur2 and H. J. Keizer1

1Department of Medical Oncology, Leiden University Medical Centre Leiden, The Netherlands
2Department of Otolaryngology and Head and Neck Surgery, Leiden University Medical Centre Leiden, The Netherlands

Correspondence to:D. ten Bokkel Huinink, MD, Diakonessenhuis, Department of Internal Medicine, Bosboomstraat I, 3582 AK Utrecht, The Netherlands, E-mail: huinink{at}worldonline.nl

Purpose: A phase I trial of raltitrexed in combination with cisplatin in patients with locally advanced or metastatic squamous cell carcinoma of the head and neck (SCCHN).

Patients and methods: Eligible patients had locally advanced or metastatic SCCHN. Cohorts of patients were treated with escalating doses of raltitrexed (2.0 mg/m2to 3.5 mg/m2) as a 15-minute intravenous infusion immediately followed by cisplatin (80 mg/m2) administered over four hours every three weeks to determine the maximum tolerated dose (MTD).

Results: A total of 17 patients was administered 60 courses of an escalating dose of raltitrexed. Starting dose of cisplatin was initially 100 mg/m2in the first three patients treated at the first dose level. Due to cisplatin-induced nephrotoxicity expressed as a creatinine clearance decrease by more than 50%, the cisplatin dose was reduced to 80 mg/m2for all subsequent treatment cycles. Dose-limiting toxicity was observed at raltitrexed dose of 3.5 mg/m2in two out of five patients.

Dose-limiting grade 4 (CTC) neutropenia, grade 4 diarrhoea, grade 3 lethargy and elevation of transaminases and bilirubine was seen in these two patients. One patient treated at the level of the MTD, died 23 days after the first cycle with unresolved gastro-intestinal toxicity. In all other dose levels toxicity was very limited. The recommended dose for further study was raltitrexed 3.0 mg/m2in combination with cisplatin 80 mg/m2. In 15 evaluable patients, we observed 9 WHO objective responses (1 complete and 8 partial). At the recommended dose level 3 partial responses were observed in five evaluable patients.

Conclusion: The regimen of raltitrexed 3.0 mg/m2followed by cisplatin 80 mg/m2on day I, every three weeks has manageable toxicity and these doses are recommended for phase II evaluation. Results indicate that this combination is active for the treatment of patients with locally advanced or metastatic SCCHN. Recently, a phase II study has been started.

cisplatin, chemotherapy, head and neck cancer, phase I, raltitrexed


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Ann OncolHome page
E. Van Cutsem, D. Cunningham, J. Maroun, A. Cervantes, and B. Glimelius
Raltitrexed: current clinical status and future directions
Ann. Onc., April 1, 2002; 13(4): 513 - 522.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.