Should Oxaliplatin Be Added to 5FU-Based Regimens in Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?
The question represents an issue of active debate. In fact, on one hand, three options are pursued by oncologists following appropriate locoregional management of locally advanced rectal cancer: no additional adjuvant chemotherapy, fluoropyrimidines alone
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Alberto Sobrero and Alessandro Pastorino
41.1 Introduction The question represents an issue of active debate. In fact, on one hand, three options are pursued by oncologists following appropriate locoregional management of locally advanced rectal cancer: no additional adjuvant chemotherapy, fluoropyrimidines alone, and oxaliplatin-based adjuvant chemotherapy. On the other hand, the last version of US National Comprehensive Cancer Network guidelines recommends the use of FOLFOX or XELOX as adjuvant treatment for stage II/III rectal cancer, irrespective of the locoregional treatment delivered [1]. The appropriate definitive answer to the question regarding the role of adjuvant oxaliplatin can be given by a trial that, after optimal locoregional management including completion of preoperative chemoradiotherapy and subsequent TME, randomizes patients with pathological stage II/III rectal cancer, therefore pathologically staged, to receive adjuvant FOLFOX/XELOX versus fluorouracil/capecitabine alone. Actually, this trial exists. It is the Korean phase II randomized ADORE trial, recently published [2]. However, in order to adequately answer such an important question, at least one appropriately powered
A. Sobrero (*) • A. Pastorino IRCCS San Martino IST, Genoa, Italy e-mail: [email protected]
phase III trial is needed, not just a phase II as the Korean study. Because other phase III trials with similar (not identical) designs exist, we will consider the results of these trials as well.
41.2 E fficacy of Adjuvant Oxaliplatin When the Locoregional Management of the Primary Cancer Has Been Optimal ADORE is a phase II trial that randomized 321 patients with pathological stage II/III rectal cancer (ypT3-T4 and/or ypN 1–2), after preoperative chemoradiation and TME, to receive adjuvant chemotherapy with FOLFOX versus FU alone. This design represents the ideal design to investigate the contribution of oxaliplatin to FU given adjuvantly. The primary end point was met with a 3-year DFS of 71.6% in the FOLFOX arm and 62.9% in the FU arm (absolute delta 8.7%, HR 0.65 p = 0.047); the 3-year OS (secondary end point of the study) was met as well with 95% OS in the FOLFOX group versus 85.7% in the FU group (HR 0.46 p = 0.036). The 9.3% gain in overall survival at 3 years for the FOLFOX arm affords a strong internal consistency of this trial. The internal validity is strengthened by the choice of the end point, the randomization after surgery so that stage II/III was pathologically proven, as well as by the intention to treat analysis. The
© Springer-Verlag Berlin Heidelberg 2018 V. Valentini et al. (eds.), Multidisciplinary Management of Rectal Cancer, https://doi.org/10.1007/978-3-319-43217-5_41
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external validity is assured by fairly large eligibility criteria (including preoperative CTRT followed by mandatory TME surgery) and by the optimal compliance to the adjuvant treatment with 93% of patients completing all chemotherapy cycles [2]. The efficacy results of this study indicate a benefit of adding oxaliplatin to a
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