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Journal of Clinical Oncology, Vol 22, No 6 (March 15), 2004: pp. 1158-1159 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.99.322
In Reply:Memorial Sloan-Kettering Cancer Center, New York, NY High-dose carboplatin and etoposide chemotherapy with stem-cell rescue is recognized as potentially curative treatment in patients with cisplatin-refractory germ cell tumors. Toxicity is formidable, and efforts have focused on eliminating treatment-related deaths, which are usually a consequence of infection or hemorrhage. Other recognized toxicities associated with high-dose carboplatin include gastrointestinal (diarrhea and abdominal cramping), and auditory (hearing loss) toxicity. Dubs et al report on neuro-otic toxicity associated with high-dose paclitaxel, ifosfamide, carboplatin, and etoposide (TICE) plus autologous stem-cell rescue, a program we previously reported in a phase I/II trial in the Journal of Clinical Oncology [1]. The optimal method for dosing of carboplatin in the high-dose setting remains an area for continued investigation. We have previously reported on the limitations of this method in the high-dose setting [2]. In our study, glomerular filtration rate (GFR) was estimated using radionuclide-labeled ligand technetium-99m diethylenetriamine penta-acetic acid (99MTe-DPTA test) [1]. We measured blood levels for carboplatin and calculated the area under the curve (AUC). The AUC measured in patients' blood was less than that predicted using the Calvert formula when GFR was estimated by 99MTe-DPTA [1]. Retrospective correlation between predicted AUC and measured AUC (from blood) suggested improved correlation when GFR was estimated by the Jelliffe formula [1]. Dubs et al did not report the method used for estimating GFR in their patients, and this would impact carboplatin dose and AUC, and toxicity. Based on the high durable complete response proportion seen in the earlier study [1], we continue to study the TICE regimen, with carboplatin dose calculated by the Calvert formula using the Jelliffe formula to estimate GFR. In total, nearly 90 patients have been treated with the TICE regimen in one or the other study at our center. Neuro-otic toxicity is observed [1], but to a lesser degree than that observed in the nine patients reported by Dubs et al. Also, we avoid exposure to other neuro-otic toxic drugs, most notably aminoglycoside antibiotics during periods of nadir fever whenever possible. The letter by Dubs et al highlights the need to continue clinical investigations in patients treated with high-dose carboplatin regimens for refractory germ cell tumors—to find the most effective and tolerable regimen and optimal dosing method for carboplatin. In this regard, improving efficacy is the primary objective, since the high-dose chemotherapy is potentially curative. Author's Disclosures of Potential Conflicts of Interest The author 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
2. Mazumdar M, Smith A, Tong WP, et al: Calvert's formula for dosing carboplatin: Overview and concerns of applicability in the high-dose setting. J Natl Cancer Inst 92:1434-1436, 2000
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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