Managing Adjuvant Treatment in Colorectal Cancer, Part II

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Researchers continue to explore the optimal duration of adjuvant chemotherapy for patients with colorectal cancer (CRC). As more data become available the standard duration has slowly declined from 18 months to the current standard of 12 cycles over the course of 6 months and a 3-month course is currently being examined.

Claus-Henning Kohne, MD, PhD, believes the most exciting research currently in stage III CRC is the examination of ever-shorter durations of treatment. Moreover, Kohne notes, it remains unclear whether FOLFOX is the optimal treatment in this space.

Axel Grothey, MD, states that approximately two-thirds of adjuvant FOLFOX efficacy is derived from fluoropyrimidine and one-third from oxaliplatin. As side effects occur, it may become necessarily to omit oxaliplatin from the regimen. In general, Grothey finds, it is a rare event for patients to complete 12 full cycles of adjuvant FOLFOX and as a result it may be best to back off treatment.

In stage II disease, Kohne and other members of the panel are reluctant to offer oxaliplatin. In general, many of the benefits of FOLFOX are derived by fluoropyrimidine alone. Omitting oxaliplatin remains especially beneficial for elderly patients, Kohne notes. However, some patients with high risk factors may still be candidates for this treatment, causing even further uncertainty. In general, the dilemma of determining which patients benefit the most from adjuvant therapy calls for effective predictive markers.

Johanna Bendell, MD, notes that studies are currently looking at high microsatellite instability (MSI) or DNA Mismatch Repair (MMR) deficiency as an indicator of resistance to fluorouracil therapy, which denotes less benefit from adjuvant therapy. Additionally, she adds, patients with Lynch Syndrome should also receive genetic testing.

In terms of gene profiling, the panel does not feel confident in the predictive accuracy of commercially available tests. In general, they feel these test are not adequately explaining recurrence and need to be further refined. The effectiveness of these tests is further confounded by non-concordant results between tests.

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