© 2004 European Society for Medical Oncology
Response to the letter "Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU and infusional 5-FU alone in advanced pancreatic carcinoma patients", by C. Allior (Ann. Oncol 2004; 15: 1576–1577)
The authors thank Dr Alliot for his thoughtful letter, and agree with most of his considerations, discussion and well thought-out approach to the possibility of finding molecular predictive factors for specific drugs or regimens. Nonetheless, some misconceptions and/or misunderstandings need to be clarified with respect to the timing and rationale for the published study [1
], so that his comments can be considered in the correct context.
Most of the authors of our paper are indeed firm advocates of the fixed rate gemcitabine infusion, which was first prospectively assessed in a comparative trial reported in abstract form in 1999 by Tempero et al. [2] as a more efficient (more active, less toxic) way to administer this agent. This led one of the participants to design the optimal GEMOX (gemcitabine–oxaliplatin) (E.C.) combination later adopted by the GERCOR group in its studies on this disease [3].
Gemcitabine was not approved for the treatment of pancreatic cancer in France until April 1998, given its minimal benefit over what we consider suboptimal (bolus) administration of 5-fluorouracil (5-FU). On the other hand, our choice of infusional 5-FU (a better way of giving 5-FU, before capecitabine became available) as a control was based on its proven marginal activity in pancreatic cancer reported for a number of published phase III studies (of which, one is referenced in our manuscript: Maisey et al. [4]). Given that our study was initiated at the time that identification of oxaliplatin–5-FU synergy was resulting in an overhaul of the treatment and natural history of advanced colon cancer, and that its activity had been reported in many other settings, we had no other alternative than to choose the correct ethical control to benchmark the combination activity exploration beyond a single-arm phase II trial, which also allowed us to obtain at the same time, once and for all, single-agent data on oxaliplatin activity in pancreatic cancer. We consider that although the results of our trial are modest and have been published in full relatively late, they provide valuable information to many colleagues, and will allow oncologists to avoid needless ‘second guessing’.
The excellent safety profile of the oxaliplatin–5-FU combination provides a valid alternative for the small but prevalent population of patients who cannot be treated with gemcitabine due to its pulmonary toxicity, a short time interval with radiotherapy, or who have failed gemcitabine–platinum-based therapies.
In summary, given that gemcitabine was not available in France at the time of the conception of this study, we considered (and still do) that the study presented was one of the best alternatives available for the treatment of pancreatic cancer patients within a clinical research initiative. Its results were beneficial to a small proportion of long-term responding patients during its conduct, and the oncologic community through its reporting.
1 Institut Gustave Roussy, Villejuif; 2 Hôpital Ambroise Paré, Boulogne; 3 Cvitkovic et Associés Consultants, Kremlin-Bicêtre; 4 Centre Paoli Calmettes, Marseille; 5 Centre Claudius Regaud, Toulouse; 6 Hôpital Avicenne, Bobigny; 7 CHU Robert Debré, Reims; 8 Clinique Armoricaine de Radiologie, St Brieuc; 9 Centre Hospitalier Intercommunal, Villeneuve St Georges; 10 Centre Hospitalier R. Dubos, Pontoise, France
* Email: e.cvitkovic{at}caconcology.com
References
1. Ducreux M, Mitry E, Ould-Kaci M et al. Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients. Ann Oncol 2004; 15: 467–473.
2. Tempero M, Plunkett W, Ruiz van Haperen et al. Randomized phase II trial of dose intense gemcitabine by standard infusion vs. fixed dose rate in metastatic pancreatic adenocarcinoma. Proc Am Soc Clin Oncol 1999; 18: 273a (Abstr).
3. Louvet C, André T, Lledo G et al. Gemcitabine combined with oxaliplatin (GEMOX) combination in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol 2002; 20: 1512–1518.
4. Maisey N, Chau I, Cunningham D et al. Multicenter randomized phase III trial comparing protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin in inoperable pancreatic cancer. J Clin Oncol 2002; 20: 3130–3136.
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