Elsevier

Oral Oncology

Volume 34, Issue 3, May 1998, Pages 224-228
Oral Oncology

Randomized trial of induction chemotherapy in larynx carcinoma

https://doi.org/10.1016/S1368-8375(97)00090-0Get rights and content

Abstract

We conducted a randomized study in patients with previously untreated advanced (T3) larynx carcinoma to compare total laryngectomy followed by radiotherapy to induction chemotherapy, followed by radiotherapy in good responders, and by total laryngectomy plus radiotherapy in poor responders. A total of 68 patients were included in the study, 36 in the induction chemotherapy group and 32 in the no chemotherapy group. 15 of the 36 patients in the induction chemotherapy group did not have a laryngectomy. Survival and disease-free survival were significantly worse in the induction chemotherapy group than in the no chemotherapy group (P=0.006 and P=0.02, respectively). The 2-year survival rates were 69% in the induction chemotherapy group and 84% in the no chemotherapy group. Larynx preservation for patients, selected on the basis of having responded to induction chemotherapy, cannot be considered a standard treatment at the present time.

Introduction

Treatment of moderately advanced or advanced resectable laryngeal cancers has long been a subject of controversy. The majority of these cancers were treated by total laryngectomy, optionally followed by radiotherapy. However, some countries (especially Northern European countries) or institutions (for example the Princess Margaret Hospital in Toronto or Institut Curie in France) preferred radiotherapy alone and reserved surgery for salvage treatment. There has been a heated debate about whether the best therapeutic approach is surgery followed by radiotherapy if needed, or radiotherapy followed by surgery if a salvage treatment is needed. It has never been possible to conduct a randomized trial comparing these two attitudes.

Until the late 1970s, chemotherapy was relatively disappointing for the treatment of head and neck cancers. The randomized trials conducted showed no benefit in terms of survival except for one trial of intra-arterial chemotherapy for tumours of the oral cavity[1]. The use of platinum salts at the end of the 1970s and of combination cisplatin and 5-FU at the beginning of the 1980s have changed the issue by leading to complete macroscopic disappearance of tumour in 30–40% of previously untreated patients. Very soon it became apparent that most chemosensitive tumours were also radiosensitive. This provided the basis for the development of a new strategy leading to larynx preservation in selected patients: after initial chemotherapy, good responders were to receive radiotherapy and poor responders were to undergo total laryngectomy.

If some teams opted for this strategy in routine practice, right from the outset, others preferred to conduct randomized studies comparing total laryngectomy to the new strategy. A study including 332 patients was conducted in the U.S.A. in the framework of the Veteran's Administration2, 3. The results of another study conducted in France by the Groupe d'Etude des Tumeurs de la Tête et du Cou (GETTEC), Head and Neck Tumor Study Group, which included 68 patients, are reported here.

Section snippets

Patients and methods

All patients with a biopsy-proven squamous cell carcinoma of the larynx, classified as T3, N0, N1, N2 a or b [UICC-AJC, 1986] and considered for total laryngectomy were included if they had a performance status index (ECOG scale) above 2, creatinine clearance ⩾60 ml/min, a white cell count ⩾4000/mm3, a platelet count ⩾100 000/mm3 and an adequate auditory and cardiac status. All patients underwent pre-treatment endoscopy for tumour staging, and measurement, and a CT scan of the larynx. Patients

Results

This trial was activated in February 1986 and closed to patient accrual in February 1989. A total of 68 patients were entered on the study, 36 assigned to the induction chemotherapy group and 32 to the no chemotherapy group. The trial was interrupted prematurely when the majority of patients refused entry because they wished to receive chemotherapy. The median follow-up was 5 years.

Patient characteristics are presented in Table 1. There were no significant differences between the treatment

Discussion

Our study shows better survival and better disease-free survival in the group treated by laryngectomy than in the group treated with induction chemotherapy. This result contradicts the result of the North American Veteran's Administration study in which survival was the same in the 2 groups. Although the 2 studies used a comparable approach, the patient populations are different: less than 60% of the population in the North American study had vocal-cord fixation whereas all the patients in the

Acknowledgements

We thank Laurence Désigné (Secretariat of Mach-NC-Meta analysis of Chemotherapy in Head and Neck Cancer) for statistical assistance and Lorna Saint-Ange for linguistic revision of the manuscript.

References (5)

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