Cisplatin/Tegafur/Uracil/Irinotecan Triple Combination Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase I/II Clinical Study

San-Chi Chen, Peter Mu-Hsin Chang, Muh-Hwa Yang, San-Chi Chen, Peter Mu-Hsin Chang, Muh-Hwa Yang

Abstract

Lessons learned: Cisplatin/tegafur/uracil/irinotecan triple combination therapy shows moderate response, especially in patients without previous chemoradiotherapy within the 6 months before this combination therapy.Toxicity is tolerable, and quality of life is improved in responders.

Background: The prognosis is poor in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Triple combination therapy may increase tumor response.

Methods: This phase I/II prospective trial first determined the dose-limiting toxicity and recommended dose of irinotecan with cisplatin and tegafur/uracil (UFUR) in phase I. Irinotecan was supplied at doses of 40, 50, 60, and 70 mg/m(2) by using a standard 3+3 design. Doses of cisplatin and UFUR were held stable. In phase II, the recommended dose of irinotecan was administered intravenously (i.v.) over 90 min on day 1, with cisplatin 50 mg/m(2) i.v. over 60 min also on day 1, and oral UFUR 200 mg twice a day for 5 days every 2 weeks a cycle.

Results: In the phase I portion, 14 patients were enrolled, and the dose level of irinotecan at 60 mg/m(2) was defined as the recommended dose for the phase II portion of the study. Among 43 patients enrolled in the phase II portion, complete response was seen in 2 patients (4.7%) and partial response in 10 patients (23.3%), and the disease control rate was 39.5%. In a subgroup analysis of patients whose prior chemoradiotherapy was more than 6 months earlier, a response rate of 40.7% and disease control rate of 59.3% were observed.

Conclusion: Cisplatin/UFUR/irinotecan triple combination therapy is tolerated and effective for selected patients. Individualized choice of treatment will influence prognosis and quality of life in R/M HNSCC patients.

©AlphaMed Press; the data published online to support this summary is the property of the authors.

Figures

Figure 1.
Figure 1.
Change in tumor burden. Waterfall plots show the maximum change from baseline in the sum of target lesions (n = 42). ∗, With new onset of bone metastasis. Abbreviation: CCRT, concurrent chemoradiotherapy.
Figure 2.
Figure 2.
Kaplan-Meier analysis of study population. (A): Progression-free survival in all cases. (B): Overall survival in all cases. (C): Progression-free survival between cases with/without CCRT in 6 months (median, 3.0 vs. 3.8 months; p = .002). (D): Overall survival between cases with/without CCRT in 6 months prior (median, 5.1 vs. 8.4 months; p = .002). Abbreviation: CCRT, concurrent chemoradiotherapy.

References

    1. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–1127.
    1. Kurzweg T, Möckelmann N, Laban S, et al. Current treatment options for recurrent/metastatic head and neck cancer: A post-ASCO 2011 update and review of last year’s literature. Eur Arch Otorhinolaryngol. 2012;269:2157–2167.
    1. Vermorken JB, Remenar E, van Herpen C, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007;357:1695–1704.
    1. Posner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007;357:1705–1715.
    1. Janinis J, Papadakou M, Xidakis E, et al. Combination chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in previously treated patients with advanced/recurrent head and neck cancer: a phase II feasibility study. Am J Clin Oncol. 2000;23:128–131.
    1. Colevas AD, Amrein PC, Gomolin H, et al. A phase II study of combined oral uracil and ftorafur with leucovorin for patients with squamous cell carcinoma of the head and neck. Cancer. 2001;92:326–331.
    1. Xie R, Mathijssen RH, Sparreboom A, et al. Clinical pharmacokinetics of irinotecan and its metabolites: A population analysis. J Clin Oncol. 2002;20:3293–3301.
    1. Gilbert J, Cmelak A, Shyr Y, et al. Phase II trial of irinotecan plus cisplatin in patients with recurrent or metastatic squamous carcinoma of the head and neck. Cancer. 2008;113:186–192.
    1. Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: A Southwest Oncology Group study. J Clin Oncol. 1992;10:1245–1251.
    1. Jacobs C, Lyman G, Velez-García E, et al. A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol. 1992;10:257–263.
    1. Gibson MK, Li Y, Murphy B, et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): An intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2005;23:3562–3567.
    1. Iyer L, Das S, Janisch L, et al. UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J. 2002;2:43–47.
    1. Huang CS, Luo GA, Huang ML, et al. Variations of the bilirubin uridine-diphosphoglucuronosyl transferase 1A1 gene in healthy Taiwanese. Pharmacogenetics. 2000;10:539–544.

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