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Université Catholique de Louvain, Brussels, Belgium
Correspondence to: Lionel Duck, MD Unité d’Oncologie Médicale, Cliniques Universitaires St-Luc, Av Hippocrate 10, 1200 Brussels, Belgium; e-mail: lionel.duck{at}onco.ucl.ac.be
To the Editor:
We read with interest the article by Kojima and colleagues (December 2003)1 concerning the treatment of a primary pulmonary angiosarcoma (AS). They used simultaneously IV recombinant interleukin-2 (rIL-2) and external radiotherapy (RX) for treating this nonmetastatic inoperable AS. Kojima and associates wrote in their article that "this combination therapy may be a promising strategy to prolong the survival of patients with primary pulmonary angiosarcoma." Although they obtained a surprising and sustained good response (more than a year) in this case, we would like to make a few comments.
rIL-2 has often been tried to treat different types of cancers. Tumor responses were observed mainly in patients with melanoma and renal cell carcinoma.2 Kojima et al mentioned the study of Masuzawa et al3 and wrote that the "systemic administration of high doses of rIL-2 was also highly effective and induced the regression of pulmonary metastasis," but these conclusions are drawn from mice only. In human AS, rIL-2 therapy was almost always used with RX or chemotherapy, and, therefore, the potential efficacy of rIL-2 by itself cannot be assessed in AS, since it is also known to be a radiosensitive tumor. Of notice, in the retrospective study (30 patients) performed by Sasaki et al,4 and referenced by Kojima et al, the four long-term survivors (ie, > 3 years) were patients with nonmetastatic AS who had been treated with rIL-2 but also with curative RX. Finally, several chemotherapeutic drugs were tested in patients with AS. A few of them showed promising activity, except for paclitaxel in skin (ie, face and scalp) ASs.5 This drug gave interesting results (eight partial and complete responses among nine patients) when used alone without RX, unlike the case with rIL-2. In our opinion, rIL-2 may be valuable in the treatment of patients with AS, but its efficacy should first be evaluated as a single agent before using it in association with RX. Moreover, one should be cautious with rIL-2 because of its potential toxicity, especially at high dosages.
References
Kumamoto University Kumamoto, Japan Kumamoto Central Hospital, Kumamoto, Japan
Correspondence to: Isamu Okamoto, MD, PhD, Department of Respiratory Medicine, Graduate School of Medical Science, Kumamoto University, 1–1-1 Honjo, Kumamoto 860-0811, Japan; e-mail: isamu{at}kaiju.medic.kumamoto-u.ac.jp
To the Editor:
We thank Duck and colleagues for their comments on our article (December 2003),1 and we appreciate the opportunity to respond. They describe in their letter that recombinant interleukin (rIL)-2 may be valuable in the treatment of primary pulmonary angiosarcoma (AS), but its efficacy should first be evaluated as a single agent before using it in association with radiotherapy. The patient in our study, who was given high doses of rIL-2 combined with radiotherapy, had no unmanageable side effects and has remained progression-free for almost 2 years after diagnosis. The excellent clinical outcome is outstanding among those previously reported in primary pulmonary AS patients, who died within months of the initial presentation. Since biological therapies, including those utilizing high-dose IL-2, differ from chemotherapeutic approaches in terms of mechanism of action, toxicity, and response profile, one should interpret the clinical activity with due caution.
We have not been able to conclude from the presented case that rIL-2 itself possesses substantial antitumor activity against primary pulmonary AS, even though evidence has been growing in a fraction of patients with metastatic melanoma and renal cell carcinoma.2 On the basis of the sensitivity of AS to radiotherapy, it is possible that concomitant radiotherapy may enhance immunogenicity by causing cellular damage and activating IL-2-stimulated cellular effectors. The consequent synergistic effects might be required to achieve the remarkable and durable response that was observed in our patient. Further investigation to explore the molecular and cellular mode of action of the combination of radiotherapy and immunotherapy will be awaited, as well as the more clinically successful experiences of this challenging disease.
References
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