Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy

Background Oral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. Objectives To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal cancer results in improved survival, disease free survival, progression free survival, locoregional control and reduced recurrence of disease. To determine which regimen and time of administration (induction, concomitant or adjuvant) is associated with better outcomes. Search strategy Electronic searches of the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, AMED were undertaken on 1st December 2010. Reference lists of recent reviews and included studies were also searched to identify further trials. Selection criteria Randomised controlled trials where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and which compared the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration, were included. Data collection and analysis Eighty-nine trials which met the inclusion criteria were assessed for risk of bias and data were extracted by two or more review authors. The primary outcome was total mortality. Trial authors were contacted for additional information or for clarification. Main results There is evidence of a small increase in overall survival associated with induction chemotherapy compared to locoregional treatment alone (25 trials), hazard ratio (HR) of mortality 0.92 (95% confidence interval (CI) 0.84 to 1.00, P = 0.06). Post-surgery adjuvant chemotherapy is associated with improved overall survival compared to surgery +/- radiotherapy alone (10 trials), HR of mortality 0.88 (95% CI 0.79 to 0.99, P = 0.03), and there is some evidence that this improvement may be greater with concomitant adjuvant chemoradiotherapy (4 trials), HR of mortality 0.84 (95% CI 0.72 to 0.98, P = 0.03). In patients with unresectable tumours, there is evidence that concomitant or alternating chemoradiotherapy is associated with improved survival compared to radiotherapy alone (26 trials), HR of mortality 0.78 (95% CI 0.73 to 0.83, P < 0.00001). These findings are confirmed by sensitivity analyses based on studies assessed at low risk of bias. There is insufficient evidence to identify which agent(s) and/or regimen(s) are the most effective. The additional toxicity attributable to chemotherapy in the combined regimens remains unquantified. Authors' conclusions Chemotherapy, in addition to radiotherapy and surgery, is associated with improved overall survival in patients with oral cavity and oropharyngeal cancers. Induction chemotherapy may prolong survival by 8 to 20% and adjuvant concomitant chemoradiotherapy may prolong survival by up to 16%. In patients with unresectable tumours, concomitant or alternating chemoradiotherapy may prolong survival by 10 to 22%. There is insufficient evidence as to which agent or regimen is most effective and the additional toxicity associated with chemotherapy given in addition to radiotherapy and/or surgery cannot be quantified.