Paris, France – During standard chemotherapy indicated after surgery for high-risk stage III colon cancer, discontinuation of oxaliplatin is possible after three months in the event of neuropathy, with no impact on recurrence-free survival or overall survival, according to an analysis of more than 10,000 patients. The results were presented at the French-speaking days of hepato-gastroenterology and digestive oncology (JFHOD 2022) [1].
In these patients receiving six months of adjuvant chemotherapy combining fluoropyrimidine and oxaliplatin (FOLFOX or CAPOX regimen), “oxaliplatin can be stopped beyond six cycles of treatment, even in the event of grade 1 neuropathy”, commented the Prof. Julien Taieb (Georges Pompidou European Hospital, Paris), which led the study, during a press conference [2]. Fluoropyrimidine, on the other hand, must be maintained until the end of treatment.
Oxaliplatin can be discontinued beyond six treatment cycles, even in the case of grade 1 neuropathy.
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Risk of irreversible neuropathy
In the management of phase 3 colon cancer with high-risk lymph node involvement (T4 and/or N2), FOLFOX (5 fluorouracil and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) chemotherapy is indicated for a duration of six months after surgery. With this adjuvant treatment, the risk of recurrence goes from 50 to 25%, specified the gastroenterologist.
Used in both treatment regimens, oxaliplatin has the disadvantage of inducing neurotoxicity which results in potentially irreversible neuropathies (pain, tingling, loss of sensation). Discontinuation of oxaliplatin is recommended in the event of grade 2 or higher neuropathy, but this indication remains questionable in less serious cases.
“Oxaliplatin has cumulative neurotoxicity. In a scheme of 12 cycles planned for six months of adjuvant chemotherapy, neuropathy generally appears between the 6th and 12th cycle”, specifies Prof. Taieb. Some are well tolerated, while others can quickly become disabling and permanent.
The meta-analysis IDEA was able to show that the duration of adjuvant chemotherapy FOLFOX or COLPOX can be reduced from six months to three months without loss of efficacy in the treatment of stage III colon cancer, but only in patients with a lower risk of recurrence. For patients at higher risk, reducing the duration of treatment should be discussed on a case-by-case basis.
Complete cessation not beneficial
In their study, the Dr. Claire Welsh (Georges Pompidou European Hospital, Paris) and his colleagues wanted to assess the benefit of early discontinuation of oxaliplatin alone compared with early discontinuation of complete chemotherapy. To do this, they used the data from the 11 trials used in IDEA, as well as in the meta-analysis ACCENT.
The data relate to 10,447 patients treated with adjuvant chemotherapy for phase III colon cancer, in two thirds of the cases with a FOLFOX regimen. Early discontinuation of complete chemotherapy and oxaliplatin alone was defined as discontinuation of treatments before 75% of the planned cycles (≤ 9 cycles for FOLFOX six months and ≤ 6 cycles for CAPOX six months).
Early discontinuation of complete chemotherapy affected 21% of patients, while oxaliplatin alone was discontinued in 19% of them. Discontinuation of treatment more often concerns women, the over 65s and individuals of low build (BMI<18.5). It is observed more with the CAPOX chemotherapy regimen, which is known to be less well tolerated.
After multifactorial adjustment, the analysis shows that stopping complete chemotherapy early has a clear impact on three-year disease-free survival (69% versus 79% in patients who had six months of treatment). Regarding five-year overall survival, the results are also in favor of maintaining treatment (75% vs 85%).
At least three months
“Finally, it is the patients receiving 100% of the chemotherapy cycles who have the best prognosis. The more the number of cycles decreases, the worse the prognosis is good”, even when more than 75% of the planned cycles have been administered, commented Dr. Gallois, during her presentation.
A subgroup analysis shows that the prognosis does not change in the event of early cessation of chemotherapy only in low-risk patients on CAPOX. This is also the standard regimen now recommended for three-month chemotherapy in these patients after the results of the IDEA meta-analysis, said Dr Gallois.
On the other hand, concerning the early discontinuation of oxaliplatin alone, the analysis does not show a significant difference with the maintenance of the treatment on the disease-free survival at three years (77.2% vs 78.3%) and on the five-year overall survival (83% vs 84%), in the low-risk group as well as in the high-risk group, regardless of the regimen used.
However, while the prognosis appears similar between patients receiving 100% of cycles of oxaliplatin and those receiving 50% or more of cycles, the three-year disease-free survival is lowered in those who have received less than 50% of cycles ( respectively 78.3%, 78.1% and 74.1%).
Not in favor of a systematic stop
When a six-month adjuvant chemotherapy prescription was decided to treat stage III colon cancer, “withdrawing oxaliplatin after three months in patients developing grade 1-2 neuropathy appears to be a valid option without have a prognostic impact”, concluded the gastroenterologist.
At the end of the session, she specified during an exchange that the analysis does not make it possible to validate a systematic discontinuation of oxaliplatin after three months of dual therapy. “We are only able to reassure on the interest of stopping the treatment as soon as neuropathy appears, which can alter the patient’s quality of life in the long term”.
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