Annals of Oncology Advance Access originally published online on July 21, 2006
Annals of Oncology 2006 17(12):1853-1854; doi:10.1093/annonc/mdl157
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© 2006 European Society for Medical Oncology
letters to the editor |
Oxaliplatin in inoperable or metastatic bladder cancer
Unité d'Oncologie Médicale, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 27, rue du faubourg Saint-Jacques 75679 Paris Cedex 14, France
* (E-mail: olivier.mir{at}cch.aphp.fr)
We read with great interest a recent paper by Bamias et al. [1] reviewing the different systemic chemotherapy combinations available for urothelial cancer patients. The authors emphasise the role of cisplatin-based combinations and mention the doublet gemcitabine–carboplatin as a useful alternative for patients who are unfit for cisplatin. This review also highlights the lack of activity of oxaliplatin in heavily pretreated patients.
We agree with the authors that in metastatic bladder cancer, objective responses are rarely observed in pretreated patients. As a result, the most interesting experience with oxaliplatin was obtained as a first-line therapy. Hence, in this review on chemotherapy in bladder cancer, the authors did not mention the activity of the gemcitabine–oxaliplatin combination in bladder cancer patients, and especially in ‘unfit’ patients [2–5].
Up to 50% of patients are unfit for cisplatin-based chemotherapy, due to a poor renal function, a poor performance status (PS) or other comorbidities (especially cardiopathy). Renal dysfunction is not only a concern for cisplatin, but also for carboplatin, since its elimination is dependent on glomerular filtration, and the exact evaluation of creatinine clearance by the Cockroft–Gault formula is insufficient in elderly patients [6]. Oxaliplatin is not nephrotoxic, has low haematotoxicity and its toxicity is not dependant on renal function [7].
To our knowledge, four studies recently assessed the role for the gemcitabine–oxaliplatin combination in urothelial cancer patients [2–5]. Irrespective of the precise treatment regimen (different drug doses were used in the four studies), the gemcitabine–oxaliplatin combination appears active and well tolerated in urothelial cancer patients [2–5], especially in frail patients with renal or cardiac comorbidities [4].
The number of patients ranged from 20 to 31 and the number of cycles ranged from 74 to 178. The reported response rates ranged from 47% to 60%. As expected, the disease extension in responders was limited to locally advanced disease or node metastases. Haematological toxicities were mild and manageable: grade 3–4 neutropenia occured in 8%–16% of patients, and grade 3–4 thrombocytopenia occurred in 1%–13% of patients. Moreover, the treatment is feasible in the outpatient setting and adverse events requiring re-hospitalisation, such as neutropenic fever, were reported in less than 10% of cycles.
The gemcitabine–oxaliplatin combination should, therefore, be evaluated in a population of unfit patients and compared with the reference regimen for these patients (gemcitabine–carboplatin or methotrexate–vinblastine–carboplatin). Previous reports indicate a favourable benefit/risk ratio of the gemcitabine–oxaliplatin regimen in the unfit patient population, in whom chemotherapy represents effective palliation.
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1. Bamias A, Tiliakos I, Karali MD, Dimopoulos MA. (2006) Systemic chemotherapy in inoperable or metastatic bladder cancer. Ann Oncol 17:553–561.
2. Font A, Esteban E, Carles J, et al. (2004) Gemcitabine and oxaliplatin combination : a multicenter phase II trial in unfit patients with locally advanced or metastatic urothelial cancer. Proc Am Soc Clin Oncol 23:391 (Abstr 4544).
3. Culine S, Rebillard X, Iborra F, et al. (2003) Gemcitabine and oxaliplatin in advanced transitional cell carcinoma of the urothelium: a pilot study. Anticancer Res 23:1903–1906.[Web of Science][Medline]
4. Mir O, Alexandre J, Ropert S, et al. (2005) Combination of gemcitabine and oxaliplatin in urothelial cancer patients with severe renal or cardiac comorbidities. Anticancer Drugs 16:1017–1021.[CrossRef][Medline]
5. Theodore C, Bidault F, Bouvet-Forteau N, et al. (2006) A phase II monocentric study of oxaliplatin in combination with gemcitabine (GEMOX) in patients with advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract. Ann Oncol (E-pub 6 April 2006).
6. Marx GM, Blake GM, Galani E, et al. (2004) Evaluation of the Cockroft-Gault, Jelliffe and Wright formulae in estimating renal function in elderly cancer patients. Ann Oncol 15:291–295.
7. Takimoto CH, Remick SC, Sharma S, et al. (2003) Dose-escalating and pharmacological study of oxaliplatin in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study. J Clin Oncol 21:2664–2672.
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