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Ototoxicity in Patients With Dose-Intensive Therapy for Cisplatin-Resistant Germ Cell Tumors

Division of Oncology, University Hospital Zürich, Zürich, Switzerland
City Hospital Triemli Zürich, Institute of Oncology and Hæmatology, Zürich, Switzerland

To the Editor:

Motzer et al [1] reported a substantial durable complete remission (rate, 57%) after dose-intense sequential, accelerated chemotherapy with paclitaxel + ifosfamide and three cycles of high-dose carboplatin + etoposide (mean target carboplatin area under the curve [AUC] of 24 [mg/mL] x minute per cycle) followed by peripheral blood-derived stem-cell support in patients with cisplatin-resistant germ cell tumors. Hearing impairment or deafness were not reported as adverse effects. Carboplatin-induced ototoxicity in different high-dose combination regimens has been described by other investigators [2,3]. Between October 2000 and August 2002, we treated nine patients with resistant or recurrent germ cell tumors according to the regimen described by Motzer et al, with three cycles of high-dose carboplatin + etoposide (carboplatin AUC of 24 [mg/mL] x minute). All patients were pretreated with as many as four cycles of cisplatin-containing chemotherapy. At the beginning of the dose-intense therapy, none of the patients had a clinically obvious hearing impairment. During treatment, all of them started to suffer from hearing disorders and finally developed a clinically manifested hearing impairment. Audiometry revealed bilateral high-frequency sensorineural hearing loss (above 2,000 Hz), with tinnitus in six patients; three of them needed a hearing aid. Hearing impairment was apparent in the other three patients as well, though audiometry was not done. Our experience confirms the favorable results in this group of patients with poor prognosis (five of nine patients are in durable complete remission; complete remission rate, 56%), whereas the ototoxicity observed with this regimen is a considerable adverse effect. Ototoxicity seems to be strongly related to the cumulative carboplatin AUC [3]. High-dose carboplatin is thought to be important to obtain favorable results in patients with relapsed or resistant germ cell tumors. Clinicians should be aware of the possible severe ototoxicity with this regimen, and patients undergoing multiple cycles of carboplatin-containing high-dose chemotherapy should be informed about this relevant toxicity.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Motzer RJ, Mazumdar M, Sheinfeld J, et al: Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients. J Clin Oncol 18:1173-1180, 2000[Abstract/Free Full Text]

2. Huitema AD, Spaander M, Mathjt RA, et al: Relationship between exposure and toxicity in high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin. Ann Oncol 13:374-384, 2002[Abstract/Free Full Text]

3. van Warmerdam LJ, Rodenhuis S, van der Wall E, et al: Pharmacokinetics and pharmaco-dynamics of carboplatin administered in a high-dose combination regimen with thiotepa, cyclophosphamide and peripheral stem cell support. Br J Cancer 73:979-984, 1996[Medline]

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