Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial)

Abstract

A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials.

EGFR-targeted poly(ethylene glycol)-distearoylphosphatidylethanolamine micelle loaded with paclitaxel for laryngeal cancer: preparation, characterization andin vitroevaluation

“…Induction chemotherapy or concurrent chemoradiotherapy is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer (Majem et al, 2006;Dietz et al, 2009;Haigentz et al, 2012). However, systemic cancer chemotherapy is frequently accompanied by strong side effects and acquired drug resistance.…”

“…Paclitaxel has a unique mechanism of action to induce the assembly and stabilization of the cellular microtubule apparatus and therefore inhibit cell division (Rowinsky & Donehower, 1995). This has led to the regulatory approval of paclitaxel in many countries for use in the therapy of patients with locally advanced laryngeal cancer or other head and neck squamous cell carcinoma (Dietz et al, 2009;Suntharalingam et al, 2012). However, its poor water-solubility seriously restricts the practical use.…”

The Role of Chemotherapy in the Management of Patients with Head and Neck Cancer

“…Paclitaxel-containing induction regimens have also been evaluated and have demonstrated improved outcomes. 23,24 Finally, induction chemotherapy has been used as a tool to guide subsequent modality selection. In this setting, a cycle of induction chemotherapy is administered followed by administration of definitive concurrent CRT to responders, whereas nonresponders undergo surgery.…”

GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers

“…3,4 Surgery followed by concurrent chemotherapy is the standard clinical treatment modality. 5 Docetaxel (DTX) is a mitotic chemotherapeutic agent widely indicated for the treatment of many malignancies. DTX acts by stabilizing the microtubule apparatus, thereby inhibiting cell division.…”