Journal of the National Cancer Institute Advance Access originally published online on August 28, 2007
JNCI Journal of the National Cancer Institute 2007 99(17):1346-1347; doi:10.1093/jnci/djm094
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© The Author 2007. Published by Oxford University Press.
CORRESPONDENCE |
Response: Re: Adjuvant Treatment of High-Risk, Radically Resected Gastric Cancer Patients with 5-Fluorouracil, Leucovorin, Cisplatin, and Epidoxorubicin in a Randomized Controlled Trial
Affiliations of authors: Clinica di Oncologia Medica, Universita' Politecnica delle Marche, Ancona, Italy (SC, MS); Oncologia Medica, Universita' Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma, Italy (CB); Oncologia Medica, Azienda Ospedaliera "Ospedali Riuniti di Bergamo," Bergamo, Italy (RL, GDB); Oncologia Medica, Istituto Clinico Humanitas, Milano, Italy (AS, CC); Oncologia Medica, Azienda Ospedaliera S. Salvatore, Pesaro, Italy (VC); Oncologia Medica, Azienda Ospedaliera di Treviglio, Treviglio, Bergamo, Italy (SB); Clinical Trials Unit, GISCAD, Milano, Italy (LF)
Correspondence to: Stefano Cascinu, MD, Clinica di Oncologia Medica, Universita' Politecnica delle Marche, Ospedali Riuniti di Ancona. Via Conca, 60020 Ancona, Italy (e-mail: cascinu{at}yahoo.com).
We have read with interest the correspondence regarding the role of pre- and postoperative chemotherapy in gastric cancer in response to our recent report of an intensive adjuvant chemotherapy in gastric cancer (1). The idea that preoperative chemotherapy may be a more suitable treatment approach for locally advanced gastric cancer is, in fact, now widely shared. Our data, along with those deriving from the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial, seem to indicate that a better tolerability profile of a perioperative treatment approach is responsible, at least in part, for the improved outcome (2). However, when our trial was designed, about 10 years ago, this was not a widespread opinion. At about the same time, the Swiss Group designed a clinical trial comparing a preoperative versus a postoperative chemotherapeutic approach with a regimen that included docetaxel. Unfortunately, at that time definitive data about activity and tolerability of docetaxel as a treatment for gastric cancer were largely lacking, making the trial design somewhat problematic. In fact, it was only last year that a randomized trial clarified the role of docetaxel in gastric cancer (3). Furthermore, our trial was designed before the MAGIC trial, when data from published literature seemed to largely support a postoperative approach (4). However, we believe that even positive results obtained with a preoperative approach may require cautious interpretation. It is important to consider that the 5-year survival in the MAGIC trial was only 23% in the control arm and 36% in the treatment arm, whereas the 5-year survival approached 50% in the control arms, both in our study and in the Italian Trials of Medical Oncology trial (5). Once again, potentially positive results may depend on the quality of surgery, and adjuvant treatment may be useful only in patients not likely to receive an optimal surgical treatment. We note that a similar interpretation was applied to results obtained with adjuvant radiotherapy in the trial of MacDonald et al. (6).
Finally, Fazio et al. seem to question the choice by the Italian Intergroup to carry out a new postoperative therapy with a chemotherapy including 5-fluorouracil, cisplatin, irinotecan, and docetaxel in a sequential manner. Although we agree with most of the comments and concerns raised in the letter, we think that this new trial is exploring a novel treatment strategy in gastric cancer by allowing the administration of several drugs but, at the same time, limiting their toxic effects. The sequential multidrug approach is biologically different from the intensive approach evaluated in our study and could not be explored with a neoadjuvant design. Preliminary safety data from this trial are encouraging. If this approach also fails to show any advantage, preoperative chemotherapy would be the only viable treatment strategy to pursue in the future.
REFERENCES
(1) Cascinu S, Labianca R, Barone C, Santoro C, Carnaghi C, Cassano A, et al. Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epi-doxorubicin in a randomized controlled trial. J Natl Cancer Inst (2007) 99:601–7.
(2) Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastro-esophageal cancer. N Engl J Med (2006) 355:11–20.
(3) Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol (2006) 24:4991–7.
(4) Mari E, Floriani I, Tinazzi A, Buda A, Belfiglio M, Valentini M, et al. Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: a meta-analysis of published randomised trials. A study of the GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell'Apparato Digerente). Ann Oncol (2000) 11:837–43.
(5) Bajetta E, Buzzoni R, Mariani L, Beretta E, Bozzetti F, Bordogna G, et al. Adjuvant chemotherapy in gastric cancer: 5-year results of a randomised study by the Italian trials in Medical Oncology (ITMO) Group. Ann Oncol (2002) 13:299–307.
(6) Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmerman GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med (2001) 345:725–30.
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J Natl Cancer Inst 2007 99: 1345-1346.
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