Abstract
Chemoradiotherapy as an alternative to surgery can be offered to patients affected by loco-regionally advanced head and neck cancer (HNC). Induction chemotherapy is a valid option, supported by few positive trials, but its real efficacy is still a matter of debate. The standard regimen for induction chemotherapy in Europe is a combination of docetaxel (75 mg/m2) and reduced dose doses of cisplatin (75 mg/m2) and 5-fluorouracil (750 mg/m2 day, for five consecutive days) (TPF). It is less toxic and more effective than the historical therapy PF (cisplatin 100 mg/m2 and fluorouracil 1,000 mg/m2/day for five consecutive days). However, in some studies treatment-related mortality has been reported to be as high as 6%. Therefore, some less toxic combinations, such as a modified TPF regimen and the combination of carboplatin plus paclitaxel have been studied. These regimens are showing promising results but deserve further validation in comparative trials. Furthermore, several trials are underway in order to enhance TPF with immune checkpoints inhibitors. Compared to chemoradiotherapy, induction chemotherapy followed by chemoradiation was shown to be non-inferior, and it could decrease the distant metastatic progression, especially in high-risk populations. For selected patients, induction chemotherapy could be a strong option. The chemoselective process that leads to immediate surgery for non-responders, the high response rate (complete responses are sometimes observed), and the survival data, are all arguments in favor of induction chemotherapy, if performed in experienced centers involving health professionals in the context of a skilled multidisciplinary team.
Highlights
Every year, over 650,000 head and neck cancer (HNC) cases are diagnosed, and they account for more than 330,000 deaths worldwide [1]
A retrospective multicentric analysis which looked at 48 patients non-candidates for TPF (PS > 1, Age > 70, cardiac failure) who were treated with the modified TPF suggested similar efficacy with a response rate (RR) of 83%, and a better tolerance with 81% of patients who completed RTX
The analyses restricted to toxicity as a cause for not-starting concomitant treatment after induction or neoadjuvant chemotherapy (IC) was reported in only two trials: in the GSTTC trial [13] it was 2.4% while in the TTCC study [11] it was 12.2% (11.7% in the TPF arm and 12.8% in the PF arm)
Summary
Over 650,000 head and neck cancer (HNC) cases are diagnosed, and they account for more than 330,000 deaths worldwide [1]. Current recommendations do not suggest cisplatin for patients with ECOG Performance Status (PS) > 1, renal failure, neurologic abnormalities, audiometric impairment, hepatic, and cardiovascular disease For these patients, alternative concurrent regimens including cetuximab or carboplatin and 5-fluorouracil (5-FU) should be considered [2]. The concomitant approach demonstrated to be the most effective one, it is not so evident how useful can be the delivering of CHT before radiation This modality, defined as induction or neoadjuvant chemotherapy (IC), has been considered an intriguing and smart option for many reasons but, after years of studies and debates, its role has not been fully established. The second trial delivered 3 cycles of TPF vs PF followed by concomitant carboplatin during RTX, in a population of patients either unresectable and of low surgical curability, or candidates for organ preservation. We will discuss on the controversial role of IC for unresectable non-laryngeal and laryngeal cancers, and the perspective for the future with the possible introduction of immunotherapy
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