Drs. Grothey and Marshall have provided an excellent review of the latest developments in palliative treatment of patients with metastatic colorectal cancer (mCRC) and associated issues. Although widely metastatic disease remains incurable, outcome for mCRC patients has improved dramatically with new agents such as oxaliplatin(Drug information on oxaliplatin) (Eloxatin), irinotecan (Camptosar), capecitabine(Drug information on capecitabine) (Xeloda), bevacizumab(Drug information on bevacizumab) (Avastin), cetuximab(Drug information on cetuximab) (Erbitux), and panitumumab (Vectibix). Medical oncologists treating mCRC are increasingly challenged with the task of integrating these drug regimens into clinical practice to provide the optimal care for their patients.

Choosing a Regimen

In a palliative setting, the question of whether to begin with irinotecan-based regimens or oxaliplatin-based combinations is frequently raised. The authors seem to recommend oxaliplatin-based first-line therapy, likely on the basis of the N9741 study in which FOLFOX (infusional fluorouracil(Drug information on fluorouracil) [5-FU], leucovorin, oxaliplatin) outperformed IFL (bolus irinotecan(Drug information on irinotecan), 5-FU, leucovorin) as well as several adjuvant trials. However, the bolus vs infusional 5-FU schedules in N9741, and limited availability of second-line therapy for subjects in the IFL arm, limit the interpretation of this finding.

Our own view is that there are no major differences in outcome whether one starts with oxaliplatin-based or irinotecan-based chemotherapy for mCRC. This is borne out by several randomized trials including a randomized phase III trial in the first-line setting[1] and a sequencing study in which survival for patients who received FOLFIRI followed by FOLFOX was similar to those receiving the regimens in reverse sequence.[2] "Stop-and-go" strategies have also been successfully explored with both regimens, as the authors note.

We agree with Drs. Grothey and Marshall that the choice of chemotherapy regimen in mCRC depends on the treatment goal for each patient. Surgery, be it resection of the primary cancer or metastectomy, remains the only modality for cure in colorectal cancer. The unfortunate patients with unresectable disease should receive optimal palliative therapy that provides the best prolongation of survival with the fewest side effects.

What about patients with mCRC—typically liver- and/or lung-confined—that may be resectable if shrinkage is obtained? In this subset of patients, the goals of therapy may change depending on response to chemotherapy. These patients should be identified early, discussed in a multidisciplinary fashion, and treated aggressively with appropriate neo-adjuvant chemotherapy.

Neoadjuvant Therapy for Initially Unresectable mCRC

Tumor response rate has nearly tripled over the past decade with contemporary colorectal chemotherapy (see Table 1). In addition, tumor shrinkage has been correlated with successful liver metastectomy in a retrospective analysis of published trials, and can help in selecting the optimal neoadjuvant regimen(s) in mCRC patients with potentially resectable metastases.[3]