Ototoxicity in locally advanced head and neck cancer patients treated with induction chemotherapy followed by intermediate or high‐dose cisplatin‐based chemoradiotherapy

Abstract

Background This study evaluated ototoxicity in locally advanced head and neck cancer patients treated in the CONDOR study with docetaxel/cisplatin/5‐fluorouracil (TPF) followed by conventional radiotherapy with concomitant cisplatin 100 mg/m2 on days 1, 22, and 43 (cis100+RT) versus accelerated radiotherapy with concomitant cisplatin weekly 40 mg/m2 (cis40+ART). Methods Sixty‐two patients were treated in this study. Audiometry was performed at baseline, during TPF, before start of chemoradiotherapy, and 1, 4, 8, and 12 months after treatment. Results A complete dataset of audiometric data was available of 12 patients treated with high‐dose cisplatin and of 11 patients treated with intermediate‐dose cisplatin. Patients in the high‐dose group showed significant more hearing loss than in the intermediate group at 4 kHz ([z = 1.98; P = .04] and 8 kHz [z = 2.07; P < .03]). Interindividual variation was high in both groups. Conclusion After induction TPF, more ototoxicity was observed in chemoradiotherapy with cis100+RT than after chemoradiotherapy with cis40+ART.

Cisplatin-associated ototoxicity amongst cervical cancer patients: A prospective cohort study in south Africa

“…Our findings on cumulative cisplatin dosage effects concur with literature [ 9 , 42 , 45 , 46 ] which reports higher cumulative doses to have a greater impact on hearing thresholds, with more patients in the high-dose group than the low-dose group reflecting a Grade 2/3 category of the NCI-CTCAE grading scale at the six-month post treatment follow-up. While Whitehorn et al [ 35 ] reported that median cumulative dosages of 180.70 mg/m 2 and 236.84 mg/m 2 were likely to result in ototoxic hearing loss for the ototoxicity-free and ototoxicity groups, respectively, our study revealed that increasing cumulative dosages from 150mg/m 2 have increasing effects in the high and extended high-frequency region bilaterally, with a plateau effect seen in the left ear at 250mg/m 2 , with no further change in hearing thresholds at increased dosages.…”

Feasibility and efficacy of chemoradiotherapy with concurrent split‑dose cisplatin after induction chemotherapy with docetaxel/cisplatin/5‑fluorouracil for locally advanced head and neck cancer

“…Furthermore, the TREMPLIN randomized phase II study, in which ICT followed by CRT using high-dose CDDP was compared with ICT followed by cetuximab plus radiotherapy for larynx preservation, revealed that residual renal dysfunction (grade 1) and grade 3-4 neuropathy were observed in 22.4 and 3.4% of cases after CRT, respectively (17). Late toxicities induced by high-dose CDDP included nephrotoxicity, neurotoxicity, and ototoxicity (17)(18)(19)(20), which are irreversible and likely to reduce quality of life in patients treated with CRT. CDDP-induced nephrotoxicity is dose-dependent and involves necrosis, apoptosis, and necroptosis of renal cells (21)(22)(23)(24).…”

Novel approach of prophylactic radiation to reduce toxicities comparing 2-step40 with 56-Gy simultaneous integrated boost intensity-modulated radiation therapy for locally advanced squamous cell carcinoma of the head and neck, an intergroup phase III trial (JCOG1912, NEW BRIDGE)

“…One significance of this trial is the prospective follow-up for late toxicities, focusing on swallowing function, hearing function, and thyroid functions. Of these, ototoxicity is caused by cochlear toxicity due to CDDP and irradiation, and is irreversible, and is likely to reduce the QOL in patients treated with CRT [ 6 ]. Although the American Speech-Language-Hearing Association and the American Academy of Audiology recommend audiological assessments before, during, and after ototoxic drug administration [ 26 , 27 ], monitoring for ototoxicity in clinical practice remains underutilized in the clinical practice.…”