Discussion
The major challenge in treating pediatric ALCL is its high rate of
relapse. Event-free survival rates have barely changed since the NHL-BFM
first tested its B-cell NHL protocol on ALCL patients in the 1980s.
Vinblastine has unusual efficacy as a single agent in relapsed ALCL when
given for prolonged durations [2,3,9]. The experience with
single-agent vinblastine in relapse therapy suggested it could be a
potential drug in frontline therapy for pediatric ALCL. However,
vinblastine inaccessibility poses a particular problem in mainland China
and in the treatment of conditions such as relapsed ALCL [10].
This is the first report of single-drug vinorelbine in pediatric
relapsed ALCL. All 4 patients achieved a CR. These results are
comparable to the data from previous single-drug vinblastine studies for
relapsed ALCL. Vinorelbine belongs to the second-generation
vinca
alkaloid compounds, which are more potent and less neurotoxic than
vinblastine and vincristine. In addition, the availability of an oral
formulation may be of particular interest in the treatment of ALCL.
Maintenance therapy was shown to be highly efficient in relapsed ALCL
and may produce durable remission [4].
Of interest, all 4 included patients received very high doses of
vincristine in their initial treatment, suggesting an absence of
cross-resistance between vinorelbine and other vinca alkaloid compounds.
Indeed, the antiproliferative cascade triggered by vinca alkaloids at
the molecular level is still unclear. About 90% of pediatric ALCL
patients are positive for ALK fusion proteins, most of them caused by
the t (2;5)(p23;q35) translocation. These translocations induce
constitutive phosphorylation of ALK that activates multiple pathways
such JAK/ATAT3, AKT/P13K, and RAS/ERK, leading to growth
factor-independent cell proliferation and inhibition of apoptosis. The
ERK pathway was found to be relevant to clinical response in predicting
the effectiveness of vinorelbine in patients with non-small cell lung
cancers [11].
In our series, the toxicity of vinorelbine has no impact on treatment
schedule. Our findings suggest that vinorelbine is a potential
therapeutic option for pediatric patients with recurrent ALCL and that
the feasibility of delivering this regimen is satisfactory. The efficacy
and safety of this single-drug regimen deserve to be evaluated on a
large scale. We are now designing a clinical trial based on single-drug
vinorelbine as salvage treatment for recurrent ALCL, which should be of
interest in regard to pediatric patients with recurrent ALCL in China.
Disclosures: The authors have no conflicts of interest or
funding to disclose.