Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma

Abstract

Patients with head and neck cancer represent 11% of the malignant tumours diagnosed in French males (Ménégoz et al, 1998). While most small tumours can be cured, a majority of the tumours are advanced and despite progress in surgery and radiotherapy, the prognosis remains poor. In the past years, systemic chemotherapy has been used in an attempt to improve the results of loco-regional treatment. Clinical trials have shown a high response rate with a combination of Cisplatinum (CDDP) and 5 Fluoro-Uracil (5FU) in head and neck carcinoma sites (Decker et al, 1983;Weaver et al, 1985;Calais et al, 1988).In 1986, we decided to investigate the efficiency of neoadjuvant chemotherapy in a single tumour site: the oropharynx with survival as the main study end-point, and event-free survival as a secondary endpoint. MATERIALS AND METHODSAll patients with a biopsy-proven squamous cell carcinoma of all sites of the oropharynx except for the posterior wall and the anterior surface of epiglottis, classified as T2 to T4, N 0 to N 2b , and M 0 (UICC-AJC, 1986) were eligible if curative treatment, either radiotherapy or surgery, was considered feasible. Patients older than 69, younger than 18 or in whom chemotherapy was contraindicated, or who had previously been treated, or with multiple tumours were excluded. Patients were randomized by telephone to receive either neoadjuvant chemotherapy or no chemotherapy. Randomization was stratified on the centre and on the local treatment which was either surgery followed or not by radiotherapy, or radiotherapy alone.The treatment planned consisted, in the study arm, of 3 chemotherapy cycles followed, if possible, by surgery and systematic radiotherapy, or if surgery was impossible by radiotherapy alone. Post-randomization consent was obtained from each patient in accordance with the law in use in France at the time of the trial.A total of 318 patients treated in 6 centres were included in the trial between 1986 and 1992. ChemotherapyChemotherapy consisted of Cisplatin (100 mg/m 2 ) given in a 1-hour i.v. infusion on day 1 followed by a 24-hour i.v. infusion of fluorouracil (1000 mg/m 2 /day) for 5 days. This treatment was repeated on day 22 unless tumour progression exceeded 25%, and repeated on day 43 only if tumour regression had been observed. 2-3 weeks after the end of chemotherapy, local treatment (surgery and/or radiotherapy) was performed. SurgeryThe operative procedure in both groups consisted of a commando procedure i.e. oropharyngeal composite resection with segmental Summary The objective of the study was to evaluate the effect of neoadjuvant chemotherapy on the survival of patients with oropharyngeal cancer. Patients with a squamous cell carcinoma of the oropharynx for whom curative radiotherapy or surgery was considered feasible were entered in a multicentric randomized trial comparing neoadjuvant chemotherapy followed by loco-regional treatment to the same locoregional treatment without chemotherapy. The loco-regional treatment consisted either of surgery plus radiotherapy or...

A Phase I/II trial of concurrent docetaxel and radiation after induction chemotherapy in patients with poor prognosis squamous cell carcinoma of the head and neck

“…Induction chemotherapy has an established role of organ preservation in the treatment of patients with laryngeal and hypopharyngeal primary tumors and has been studied as a route to achieve organ preservation in other head and neck sites. [1][2][3][4][5][6] The most frequently used radiation schedule after induction therapy has been daily treatment at a dose of 1.8 -2.0 Gy per day up to a total dose of 65-70 Gy, although other schedules have been used. This approach has yielded acceptable results overall in terms of functional preservation, although the outcome for patients who do not respond well to induction treatment has not been good.…”

“…[1][2][3][4][5][6] Phase III studies have demonstrated the efficacy of combined chemotherapy and radiation for maintaining a functional larynx for patients with either a laryngeal or hypopharyngeal primary tumor without altering survival and for improving survival in patients with unresectable disease. 1,[3][4][5][6] Patients who do not have a significant response to the first two cycles of chemotherapy frequently go directly to surgery or radiation therapy. A common finding in these trials is that patients who achieve a primary site clinical and/or pathologic complete response (CR) to three cycles of induction chemotherapy fare well in terms of local disease control.…”

Docetaxel, cisplatin, and 5‐fluorouracil‐based induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

“…Despite advances in our understanding of the biology of this disease, improvements in surgical and radiation therapy techniques, and the additional impact of chemotherapy and combined-modality approaches, longterm survival in patients with locally advanced disease, measured as 2-year and 3-year overall survival (OS) and progression free survival, has remained Ͻ 50% in randomized trials. [2][3][4][5] Combination chemotherapy with cisplatin and fluorouracil (PF) is the most commonly used induction regimen in the treatment of patients with locally advanced SCCHN. The original PF chemotherapy regimen results in major response rates of 60 -90% and complete responses (CRs) in the range of 20 -50%.…”

“…3,4,6 PF is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation. [2][3][4][5] Induction chemotherapy with PF also has shown improved survival in patients with both unresectable and resectable disease when chemotherapy was followed by standard fractionated radiotherapy and when postradiation surgery for lymph node disease was included in the treatment. 2,6 It should be noted, however, that this is not a generally accepted approach and does not represent the standard of care.…”

State-of-the-art management of locally advanced head and neck cancer

“…This was presumably from micrometastatic disease that local therapy or lower dose chemotherapy as part of chemoradiation would not adequately treat. This theoretical argument has been tested in several trials that have been unable to show a consistent survival benefit Schuller et al, 1988;Paccagnella et al, 1994;El-Sayed and Nelson 1996;Domenge et al, 2000;Pignon et al, 2000). (Table 4a).…”