© 2007 European Society for Medical Oncology
letters to the editor |
Re: Perabo FGE and Muller SC. New agents for treatment of advanced transitional cell carcinoma. Ann Oncol 2007; 18: 835–843.
In their very interesting review-article, Perabo and Muller discuss the timing and selection of patients to treat for advanced transitional cell carcinoma (ATCC), giving a comprehensive overview of new active chemotherapeutic and molecular targeting agents [1]. The authors appropriately conclude that from the results of ongoing studies and identification of accurate markers of outcome and biologic activity, we will better define the future scenario of ATCC management.In the last months, just after the cited review, some new data have been released, that we believe deserve the attention of the whole uro-oncology community.
- The authors did not discuss the role of taxanes in this article. In Journal of Urology, January 2007, Lin et al, have published a phase II trial of weekly paclitaxel, cisplatin plus 5-fluorouracil and leucovorin for ATCC, as first line chemoptherapy. Of 40 eligible patients for response evaluation, 11 (28%) and 19 (48%) were complete and partial responders with overall response rate of 76%. Median overal and progression-free survival was 17 and 8.3 months, respectively. The treatment was well tolerated [2]. The response to docetaxel plus gemcitabine was evaluated in a phase II by Dumez et al, published on Anticancer Drugs. 34 patients, of whom seven had prior chemotherapy and 27 were chemotherapy-naïve were enrolled. Complete and partial remission were observed in 2 and 16 patients, for an overall response rate of 53%; toxicity was manageable [3]. Those preliminary data show a promising activity of taxanes which are meritorious of further evaluation in first and second line.
- In this review preliminary data, presented at ASCO meeting in 2005, of a combined treatment with pemetrexed-gemcitabine were discussed. Finally, the complete results have been published by Annals of Oncology. Among 47 patients, overall response rate was 28%, median response duration was 11.2 months and median overall survival 10.3 months. The combination of pemetrexed and gemicitabine was well tolerated [4]. We believe that only a randomized phase III could demonstrate the superiority of pemetrexed-gemcitabine combination respect to gemcitabine alone.
- The authors correctly stated that one of the future goals is to identify the molecular basis of bladder cancer genesis and progression. Karam et al, have published an interesting article in Lancet Oncology, investigating expression of the apoptosis markers bcl-2, caspase-3, p53 and survivin and the association with oncological outcomes of 226 patients treated by radical cystectomy for urothelial carcinoma of bladder. Expression of bcl-2, caspase-3, p53 and survivin was alterated in 32%, 49%, 53% and 64% patients, respectively. By multivariate analysis, alteration of four markers was independently associated with high rates of disease recurrence and disease-specific mortality. The four markers had a cooperative effect on progression of bladder cancer [5].
These findings show that the ‘new era’ for ATCC patients has just begun. Assessment of combined apoptosis marker status and number of altered markers in patients treated by radical cystectomy will provide prognostic information that could help to identify those at high risk for disease recurrence and mortality, who could benefit from early adjuvant treatment.
Much efforts from investigators worldwide will clarify the optimum strategy for these patients and the most appropriate timing for chemotherapeutic/molecular targeting therapies. Future approaches will be mostly directed to find out how to deal with expected failures of the standard gemcitabine-cisplatin therapy. In this setting, two main aims should be taken into account: to improve the survival and always to preserve patients' quality of life.
1 Cattedra di Oncologia Medica, Dip. di Endocrinologia e Oncologia Molecolare e Clinica, Università degli Studi Federico II, Napoli, Italy
* E-mail: giuseppedilorenzoncol{at}hotmail.com
References
1. Perabo FGE, Muller SC. New agents for treatment of advanced transitional cell carcinoma. Ann Oncol. 2007; 18: 835–843.[CrossRef][Web of Science][Medline]
2. Lin CC, Hsu CH, Huang CY, et al. Phase II trial of weekly paclitaxel, cisplatin, plus Infusional high dose 5-fluorouracil and leucovorin for metastatic urothelial carcinoma. J Urol (2007) 177:84–89.[CrossRef][Web of Science][Medline]
3. Dumez H, Martens M. Selleslach J et al. Anticancer Drugs (2007) 18:211–218.[CrossRef][Medline]
4. Von der Maase H, Lehmann J, Gravis G, et al. A phase II trial of pemetrexed plus gemcitabine in locally advanced and/or metastatic transitional cell carcinoma of the urothelium. Ann Oncol (2006) 17:1533–1538.
5. Karam JA, Latan Y, Karakiewicz PI, et al. Use of combined apoptosis biomarkers for prediction of bladder cancer recurrence and mortality after radical cystectomy. Lancet Oncol (2007) 8:128–136.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||