How many cycles of FOLFOX (Flox- Desktop Combination of Flu- Desertorin, Oxacillin, and Flu--6905) are given prior to maintenance 5-Fluorouracil (5-FU)?

From the Guidelines

Typically, 6 cycles of FOLFOX are given prior to transitioning to maintenance 5-FU therapy for metastatic colorectal cancer, as evidenced by the phase II OPTIMOX2 trial 1.

Background

The FOLFOX regimen, which consists of oxaliplatin, leucovorin, and 5-fluorouracil (5-FU), is a common treatment approach for metastatic colorectal cancer. The use of oxaliplatin has been associated with an increased incidence of peripheral sensory neuropathy, which can be mitigated by adjusting the schedule or timing of administration 1.

Treatment Approach

The decision to switch to maintenance therapy is based on treatment response, toxicity profile, and patient tolerance. Some patients may receive fewer cycles before transitioning if they develop significant neuropathy, while others might receive up to 12 cycles if well-tolerated and showing continued response. Maintenance therapy allows for continued disease control with reduced toxicity, potentially improving quality of life while preserving the option to reintroduce oxaliplatin later if needed.

Key Considerations

• The phase III EORTC 40983 study showed absolute improvements in 3-year PFS of 8.1% and 9.2% for all eligible patients and all resected patients, respectively, when chemotherapy in conjunction with surgery was compared with surgery alone 1.
• The OPTIMOX1 study demonstrated that a "stop-and-go" approach using oxaliplatin-free intervals resulted in decreased neurotoxicity but did not affect OS in patients receiving FOLFOX as initial therapy for metastatic disease 1.
• A recent meta-analysis of RCTs concluded that intermittent delivery of systemic therapy does not compromise OS compared with continuous treatment 1.

Recommendation

Based on the most recent and highest quality evidence, 6 cycles of FOLFOX are recommended prior to transitioning to maintenance 5-FU therapy for metastatic colorectal cancer 1. This approach helps manage cumulative neurotoxicity from oxaliplatin while maintaining disease control, and allows for continued disease control with reduced toxicity, potentially improving quality of life.

From the Research

FOLFOX Cycles Prior to Maintenance 5-Fluorouracil (5-FU)

• The number of FOLFOX cycles given prior to maintenance 5-FU varies across different studies, with some studies specifying the number of cycles and others not providing this information.
• In the study by 2, oxaliplatin was withdrawn electively after 8 cycles of treatment, and patients were maintained on 5-fluorouracil/leucovorin and bevacizumab until progression.
• In the study by 3, patients received six cycles of modified FOLFOX6 (mFOLFOX6) followed by maintenance therapy with oral S-1, and reintroduction of mFOLFOX6 was scheduled after four cycles of S-1 or upon tumor progression.
• In the study by 4, patients received 6 cycles of modified FOLFOX7 (5-FU/folinic acid and oxaliplatin) with aflibercept at 4 mg/kg every 2 weeks followed by maintenance therapy with fluoropyrimidine with aflibercept until disease progression or limiting toxicity.
• The study by 5 performed two cycles of mFOLFOX 6 therapy, but it does not specify that this is the standard number of cycles prior to maintenance 5-FU.
• The study by 6 does not provide information on the number of FOLFOX cycles given prior to maintenance 5-FU.

Key Findings

• The number of FOLFOX cycles prior to maintenance 5-FU is not consistently reported across studies.
• Some studies, such as 2 and 3, specify the number of cycles (8 and 6, respectively), while others, such as 5 and 6, do not provide this information or provide different cycle numbers.
• The study by 4 also specifies 6 cycles of FOLFOX prior to maintenance therapy.