Controversy Over Value of Interferon Use in Chemotherapy
Controversy Over Value of Interferon Use in Chemotherapy
Frequent recurrence and early relapse despite an excellent response to initial chemotherapy remain the hallmarks of low-grade non-Hodgkin lymphoma (NHL). Various strategies have been tried to prolong the duration of response and prevent the high frequency of relapse in this disease. One such strategy is use of interferon (IFN) in the management of follicular NHL. Some trial results suggest that IFN is efficacious, while others dispute this. The contradictory findings among trials may be a result of heterogeneity in trial design. Rohatiner and colleagues discuss these trials, noting that the use of IFN to enhance and increase the efficacy of alkylating-agent chemotherapy emerged from 2 early murine studies, one by Gresser and colleagues in 1978 and the other by Balkwill and Moodie in 1984. The first study reported a 200% increase in survival of AKR mice treated with a combination of IFN and cyclophosphamide. The second study, which examined breast cancer xenografted into nude mice, confirmed a synergistic response and showed that the antitumor effect was greatest when the 2 drugs were given concomitantly rather than subsequently.
In light of these studies, numerous trials have been conducted to assess the efficacy of IFN in the management of human indolent NHL. Studies by Smalley and colleagues, Solal-Celigny and colleagues, Andersen and Smalley, and Arranz and colleagues all showed a prolonged duration of remission when IFN was used as a part of the initial treatment. The study by Solal-Celigny and others from the Groupe d'Etude des Lymphomes de l'Adulte also demonstrated prolongation of survival in patients with low-grade NHL. In this study, IFN was used in the initial treatment as well as in the maintenance phase. However, 2 subsequent studies that mainly were designed to assess the role of IFN in maintenance therapy found that use of IFN did not result in prolongation of survival. Numerous other national and international trials that focused on the role of IFN in the treatment of NHL and/or maintenance therapy for NHL, including one conducted by the European Organization for the Research and Treatment of Cancer and another conducted by the Southwest Oncology Group, reported conflicting results.
Rohatiner and colleagues' study attempts to settle this controversy. Their study design appears to be more precise than past trials, and the investigators seem to have made efforts to avoid the variability that exists in trials addressing IFN in the management of low-grade lymphoma. This was achieved by including only patients with follicular histology.
The study results revealed that no advantage was achieved by adding IFN in either initial therapy or the maintenance phase. This well-designed study, therefore, is an important one in that its findings may help settle the controversial role of IFN in the management of low-grade NHL. It shows that there is no benefit in adding the extra toxicity of IFN to a chemotherapeutic regimen for this disease.
Frequent recurrence and early relapse despite an excellent response to initial chemotherapy remain the hallmarks of low-grade non-Hodgkin lymphoma (NHL). Various strategies have been tried to prolong the duration of response and prevent the high frequency of relapse in this disease. One such strategy is use of interferon (IFN) in the management of follicular NHL. Some trial results suggest that IFN is efficacious, while others dispute this. The contradictory findings among trials may be a result of heterogeneity in trial design. Rohatiner and colleagues discuss these trials, noting that the use of IFN to enhance and increase the efficacy of alkylating-agent chemotherapy emerged from 2 early murine studies, one by Gresser and colleagues in 1978 and the other by Balkwill and Moodie in 1984. The first study reported a 200% increase in survival of AKR mice treated with a combination of IFN and cyclophosphamide. The second study, which examined breast cancer xenografted into nude mice, confirmed a synergistic response and showed that the antitumor effect was greatest when the 2 drugs were given concomitantly rather than subsequently.
In light of these studies, numerous trials have been conducted to assess the efficacy of IFN in the management of human indolent NHL. Studies by Smalley and colleagues, Solal-Celigny and colleagues, Andersen and Smalley, and Arranz and colleagues all showed a prolonged duration of remission when IFN was used as a part of the initial treatment. The study by Solal-Celigny and others from the Groupe d'Etude des Lymphomes de l'Adulte also demonstrated prolongation of survival in patients with low-grade NHL. In this study, IFN was used in the initial treatment as well as in the maintenance phase. However, 2 subsequent studies that mainly were designed to assess the role of IFN in maintenance therapy found that use of IFN did not result in prolongation of survival. Numerous other national and international trials that focused on the role of IFN in the treatment of NHL and/or maintenance therapy for NHL, including one conducted by the European Organization for the Research and Treatment of Cancer and another conducted by the Southwest Oncology Group, reported conflicting results.
Rohatiner and colleagues' study attempts to settle this controversy. Their study design appears to be more precise than past trials, and the investigators seem to have made efforts to avoid the variability that exists in trials addressing IFN in the management of low-grade lymphoma. This was achieved by including only patients with follicular histology.
The study results revealed that no advantage was achieved by adding IFN in either initial therapy or the maintenance phase. This well-designed study, therefore, is an important one in that its findings may help settle the controversial role of IFN in the management of low-grade NHL. It shows that there is no benefit in adding the extra toxicity of IFN to a chemotherapeutic regimen for this disease.
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