Chemotherapy Alone for Laryngeal Preservation—Is It Possible?

Abstract

Holsinger et al 1 report the results of a phase II trial testing chemotherapy alone as definitive treatment for preservation of the larynx in selected patients with stages II to IV laryngeal cancer. This study is the first of its kind in the United States, even though the approach has been tried in France by Laccourreye et al 2,3 in patients with T1 to T3N0 glottic cancers. In their study, Holsinger et al were careful to select patients with T2 to T4 cancers of the glottic or supraglottic larynx who could be treated with conservation laryngeal surgery. Using a regimen of cisplatin plus ifosfamide plus paclitaxel (TIP), chemotherapy alone proved successful, with no local or regional failures in 10 patients (32%) demonstrating biopsy-confirmed complete response (CR) out of 31 patients enrolled. These results are important because they underscore the sensitivity of squamous cell cancer of the larynx to cisplatin-based chemotherapy, the potential for chemotherapy as a single-modality treatment option in selected patients with laryngeal cancer, conservation laryngeal surgery as an organ-preserving option for appropriate patients selected by an experienced team, and the importance of a multidisciplinary care team in the evaluation, management, and follow-up of patients with head and neck cancer. Seven years were required for the accrual of nine patients with T3 or T4, N0 or N1 cancers suitable for conservation laryngeal surgery, in addition to the 22 patients with T2N0 or N1 cancers who were identified as being at high risk for recurrence with altered fractionation radiotherapy, and who were also candidates for conservation laryngeal surgery. These 31 patients, all of whom had excellent performance status, received either three or four cycles of TIP followed by response assessment. All patients achieved either a CR or partial response to TIP. If a CR was determined on the basis of imaging, endoscopic examination, and negative biopsy, additional cycles of TIP were administered (up to a maximum of six cycles), after which patients were rigorously monitored. Patients with less than a biopsy-proven CR underwent appropriate laryngeal surgery, with or without neck dissection and radiation, as indicated. A high rate of laryngeal preservation was achieved (83%; 95% CI, 65 to 94), significantly better than the rate of 60%, which had been determined— on the basis of previous studies 4,5 of stage III and IV laryngeal cancers treated for organ preservation in patients in whom total laryngectomy would otherwise have been required— sufficient for declaring the treatment a success. Clearly, the bar had been set too low for this patient group, in which stage II disease was predominant, and which was suitable for conservation laryngeal surgery from the outset. The estimated survival outcomes at 5 years were an overall survival of 83% (95% CI, 70 to 98) and a recurrence-free survival (deaths not resulting from study cancer were censored) of 73% (95% CI, 58 to 91), suggesting that the treatment approach was not detrimental. Standard of care management of laryngeal cancer varies with