Ototoxicity Due to Cis-diamminedichloro-platinum in the Treatment of Ovarian Cancer

Waters, Gloria; Ahmad, Maheen; Katsarkas, Athanasias; Stanimir, G.; McKay, Jan

doi:10.1097/00003446-199104000-00003

Cited by 75 publications

(39 citation statements)

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“…In a previous study, we have shown that schedules containing daily low-dose cisplatin are less ototoxic than those containing higher daily doses [10]. This was in accordance with the findings of other studies [11,12,13]. The exact nature of morphological, electrophysiological and biochemical toxicity of cisplatin remains to be determined.…”

Section: Introductionsupporting

confidence: 89%

Characteristics and Risk Factors of Cisplatin-Induced Ototoxicity in Testicular Cancer Patients Detected by Distorsion Product Otoacoustic Emission

et al. 2006

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Objective: The characteristics and risk factors of the long-term ototoxic effect of cisplatin in testicular cancer patients was studied by measuring distortion product otoacoustic emissions (DPOAEs), which is a highly sensitive, new method for detecting high-frequency hearing loss. Methods: 223 patients with a median follow-up time of 4.27 years (range 0.5–20 years) and a median age of 37 years (range 18–55 years) were assessed by DPOAE. 100 mg/m² cisplatin were administered per cycle, in EP, BEP, VeIP, VIP or VPB regimens. The control group consisted of 40 testicular cancer patients without chemotherapy (median age 35 years, range 16–54 years). A detailed medical history evaluated audiological risk factors and hearing complaints. DPOAE was measured in eight frequencies from 750 to 8,000 Hz. Paired t test and Mann-Whitney test were used for statistical evaluation. Results: Symptomatic ototoxicity was observed in 20% of the patients. In patients receiving ≤300 mg/m² cisplatin, no amplitude changes were detected. Beyond this dose, hearing impairment proved to be dose dependent. Contrary to the literature, not only high frequencies were affected. In patients receiving ≧400 mg/m², our method could detect significant hearing impairment at lower frequencies that are important for speech perception. At 400 mg/m², significant amplitude change was detected at 3,000 Hz (p = 0.01); at 500–600 mg/m², significant amplitude change was detected at 1,500, 2,000 and 3,000 Hz (p = 0.004, 0.0001 and 0.0002, respectively), and at 700 mg/m² significant amplitude change was detected at 3,000 Hz (p = 0.01). We detected the lowest amplitudes in those 44 patients who had symptomatic ototoxicity. The only statistically significant risk factor was the cumulative dose of cisplatin; neither smoking nor noise exposure were independent risk factors. Conclusion: DPOAE is a fast, noninvasive and reliable method in detecting late ototoxicity in testicular cancer patients. Contrary to the literature, not only high frequencies are affected. In patients receiving at least 400 mg/m², using DPOAE we were able to detect significant hearing impairment at lower frequencies that are important for speech perception.

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Section: Introductionsupporting

confidence: 89%

Characteristics and Risk Factors of Cisplatin-Induced Ototoxicity in Testicular Cancer Patients Detected by Distorsion Product Otoacoustic Emission

et al. 2006

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“…It has been controversially discussed whether high single doses or high cumulative doses of cisplatin are more important for the development of persisting ototoxicity (Nakai et al, 1982;Reddel et al, 1982;Vermorken et al, 1983;Schaefer et al, 1985;Bissett et al, 1990;Boyer et al, 1990;Stuart et al, 1990;Waters et al, 1991;Hallmark et al, 1992;Saito and Aran, 1994). In our patients, audiometric threshold deviations compatible with persisting ototoxicity were seen in all patients with the application of high single doses of cisplatin (35-50 mg m-2) when cumulative doses > 550 mg m-2 were reached and in all patients with cisplatin > 600 mg m-2, regardless of the single dose given.…”

Section: Discussionmentioning

confidence: 99%

Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer

Bokemeyer

Berger²,

Hartmann³

et al. 1998

Br J Cancer

288

179

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Summary This study evaluates the degree and relevance of persisting ototoxicity after cisplatin-based standard-dose chemotherapy for testicular cancer, with emphasis on identification of potential factors for an increased risk of this late sequel. Hearing thresholds of 86 patients with a median age of 31 years (range 21-53 years) and a median follow-up time of 58 months (range 15-159 months) were assessed by conventional pure-tone audiometry. Interviews were conducted evaluating the patients' history with special regard to audiological risk factors, as well as circumstances of ototoxic symptoms. Details concerning treatment and patient variables were extracted retrospectively from the patients' charts. An additional screening programme assessed current body functions, blood parameters and other late toxicities. Symptomatic ototoxicity persisted in 20% of patients (59% tinnitus, 18% hearing loss, 23% both), while 10% had experienced completely reversible ototoxic symptoms for a duration of 1-18 months after treatment. Symptoms were bilateral in 81 % of patients. Hearing thresholds were compatible with cisplatin-induced hearing loss in 42% of audiograms performed. Subjective (history) and objective (audiogram) findings were not always consistent. The following statistically significant risk factors for ototoxicity were established: high cumulative dose of cisplatin (P < 0.0001); history of noise exposure (P = 0.006). Additionally, high doses of vincristine (P = 0.001) seemed to result in reversible ototoxic symptoms. No other independent risk factors were identified. In conclusion, persisting ototoxicity represents a clinical sequel for approximately 20% of testicular cancer patients treated at standard dose but may affect more than 50% of patients receiving cumulative doses of cisplatin > 400 mg m-2. Previous noise exposure may also result in a threefold increased risk for cisplatin ototoxicity. Future studies should use these risk factors as important stratification criteria for trials aiming at the evaluation and prevention of cisplatin-induced ototoxicity.Keywords: chemotherapy; ototoxicity; long-term toxicity; testicular cancerThe ototoxic potential of the chemotherapeutic agent cisplatin was recognized 2 decades ago (Piel et al, 1974). Despite the widespread use of cisplatin in standard treatment protocols for testicular, ovarian, head and neck, lung and other types of cancers, data on the frequencies of ototoxicity are not consistent, and risk factors have not been clearly identified so far. The measurement of the auditory function is limited because of the different diagnostic methods used for objective assessment and the subjective perception of symptoms; patients' characteristics, such as age or noise exposure, may additionally influence the hearing ability and different definitions of 'normal' and 'abnormal' hearing thresholds may also cause further discrepancies in reported results.In the current study the auditory function was evaluated in a homogeneous group of young men receiving cisplatin-based com...

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“…In the present study, we used two types of CDDP administration [i.e., a single high dose of CDDP (10 mg/kg, intraperitoneally) and a multiple dose of CDDP (2 mg/kg/d, intraperitoneally, for 5 days)] that correspond to the high therapeutic doses of CDDP used to manage human cancers (12). When compared with multiple doses of CDDP, a single high-dose administration resulted in a similar pattern of hearing loss that occurred more rapidly (i.e., 6 versus 3 days, respectively) but remained stable for at least 6 days (Fig.…”

Section: Functional and Morphologic Assessment Of Hair Cell Integritymentioning

confidence: 99%

Caspase Inhibitors, but not c-Jun NH2-Terminal Kinase Inhibitor Treatment, Prevent Cisplatin-Induced Hearing Loss

et al. 2004

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Ototoxicity Due to Cis-diamminedichloro-platinum in the Treatment of Ovarian Cancer

Cited by 75 publications

References 0 publications

Characteristics and Risk Factors of Cisplatin-Induced Ototoxicity in Testicular Cancer Patients Detected by Distorsion Product Otoacoustic Emission

Characteristics and Risk Factors of Cisplatin-Induced Ototoxicity in Testicular Cancer Patients Detected by Distorsion Product Otoacoustic Emission

Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer

Caspase Inhibitors, but not c-Jun NH2-Terminal Kinase Inhibitor Treatment, Prevent Cisplatin-Induced Hearing Loss

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