Chemotherapy sequence in advanced colorectal cancer

July 2023

Phase III studies have shown the advantage of combining chemotherapy agents fluorouracil (5-FU) with folinic acid (leucovorin) and either irinotecan or oxaliplatin compared to 5-FU + folinic acid alone for the treatment of metastatic colorectal cancer (mCRC).

A recent phase III study aimed to investigate two different chemotherapy sequences:

1. folinic acid, fluorouracil, and irinotecan (FOLFIRI), followed by folinic acid, fluorouracil, and oxaliplatin (FOLFOX6);

2. FOLFOX6 followed by FOLFIRI.

The researchers evaluated whether the sequence of these chemotherapy combinations impacted the efficacy and safety in patients with mCRC with no prior treatment for advanced colorectal cancer.

The study

Previously untreated patients with mCRC were randomly assigned to receive either FOLFIRI followed by FOLFOX6 (arm A), or FOLFOX6 followed by FOLFIRI (arm B). A total of 109 patients in arm A and 111 patients in arm B were included in the analysis.

Response rate: the percentage of people in the study or treatment group who have a partial response or a complete response to the treatment within a certain period of time (National Cancer Institute)

Progression-free survival: the length of time during and after treatment of a disease like cancer that a patient lives with the disease but it does not get worse (National Cancer Institute)

Median survival was 21.5 months in arm A compared to 20.6 months in arm B. As first-line (initial) therapy, both FOLFIRI and FOLFOX6 achieved similar response rates (56% vs 54%, respectively), and median progression-free survival rates (8.5 months vs 8.0 months, respectively). In second-line therapy, FOLFOX6 had a higher response rate (15% vs 4%) and longer median progression-free survival (4.2 months vs. 2.5 months) compared to FOLFIRI. In terms of toxicity, FOLFIRI was associated with higher rates of mucositis, nausea/vomiting, and alopecia, while FOLFOX6 had higher rates of neutropenia and neuropathy.

Conclusion

Both treatment sequences, FOLFIRI-FOLFOX6 and FOLFOX6-FOLFIRI, showed prolonged survival and similar efficacy in patients with mCRC. The toxicity profiles, however, differed between the two sequences. As such, the choice of treatment sequence should be dependant on patient-specific factors and toxicity concerns.