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Renal-Cell Carcinoma
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     To the Editor: The review of renal-cell carcinoma by Cohen and McGovern (Dec. 8 issue)1 was extensive but did not discuss radiotherapy. As noted in the article, nearly half the patients with renal-cell carcinoma have metastatic disease on presentation or will have a recurrence. Conventional radiotherapy has been an effective palliative treatment for most sites of metastatic renal-cell carcinoma, including lung, bone, and soft tissues.2 In particular, stereotactic radiosurgery has been reported to have local control rates for brain metastases of more than 85 percent.3 Recently, stereotactic radiosurgery for spinal metastases has demonstrated high efficacy in pain relief with minimal toxic effects from radiation.4 In addition, stereotactic body-radiation therapy — which allows for more conformal, high-dose extracranial radiation delivery — may expand the role of radiation in treating both metastatic and nonoperative primary cases.5 Radiation combined with biologic agents also holds promise in overcoming renal cancer-cell radioresistance and is a topic of investigation.

    Lucius Doh, M.D.

    Amarinthia E. Curtis, M.D.

    Bin S. Teh, M.D.

    Baylor College of Medicine

    Houston, TX 77030

    References

    Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med 2005;353:2477-2490.

    DiBiase SJ, Valicenti RK, Schultz D, Xie Y, Gomella LG, Corn BW. Palliative irradiation for focally symptomatic metastatic renal cell carcinoma: support for dose escalation based on a biological model. J Urol 1997;158:746-749.

    Sheehan JP, Sun MH, Kondziolka D, Flickinger J, Lunsford LD. Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control. J Neurosurg 2003;98:342-349.

    Gerszten PC, Burton SA, Ozhasoglu C, et al. Stereotactic radiosurgery for spinal metastases from renal cell carcinoma. J Neurosurg Spine 2005;3:288-295.

    Wersall PJ, Blomgren H, Lax I, et al. Extracranial stereotactic radiotherapy for primary and metastatic renal cell carcinoma. Radiother Oncol 2005;77:88-95.

    To the Editor: Cohen and McGovern do not describe the best way of administering interleukin-2 and do not fully describe the clinical trials that support the use of inpatient high-dose bolus interleukin-2 as a standard method of treatment for metastatic or locally advanced renal-cell carcinoma. For example, McDermott and colleagues published a report from the Cytokine Working Group1 suggesting that high-dose bolus interleukin 2 produces significantly more responses of apparent better quality (and a borderline significant difference in the number of patients who were progression-free at three years) relative to low-dose subcutaneous outpatient interleukin-2 and interferon alfa. Consequently, we think high-dose interleukin-2 should be the preferred therapy for appropriately selected patients with access to such therapy.

    We would like to stress that subcutaneous administration of low-dose interleukin-2 (with or without interferon alfa) should not be considered as first-line treatment of metastatic renal-cell carcinoma.

    Bruno Vincenzi, M.D.

    Daniele Santini, M.D., Ph.D.

    Giuseppe Tonini, M.D., Ph.D.

    University Campus Bio-Medico, Rome

    00155 Rome, Italy

    b.vincenzi@unicampus.it

    References

    McDermott DF, Regan MM, Clark JI, et al. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 2005;23:133-141.

    The authors reply: Doh and colleagues make an important point about the use of radiotherapy in the treatment of metastatic renal-cell carcinoma. We agree that radiotherapy serves a key role in the palliation of metastatic lesions. However, we chose to focus on more specific therapies for renal-cell carcinoma in our review, given the limitations of space. Authors of more extensive reviews than ours on renal-cell carcinoma have made a similar choice1; nevertheless, the point is well taken.

    Vincenzi and colleagues would have preferred that we were more definitive in recommending high-dose interleukin-2 as first-line therapy over subcutaneous, low-dose interleukin-2. We agree that high-dose interleukin-2 is the preferred approach for treatment of metastatic or locally advanced renal-cell carcinoma on the basis of published data. However, not all patients can tolerate high-dose interleukin-2. Indeed, as we wrote, "High-dose interleukin-2 is the standard therapy for advanced renal-cell carcinoma and is the only regimen for this disease approved by the Food and Drug Administration." We also said, "High-dose interleukin-2 induces responses in 21 percent of patients, as compared with only 13 percent of patients who receive low-dose interleukin-2."2 We could have cited the McDermott study as well.

    Herbert T. Cohen, M.D.

    Boston University School of Medicine

    Boston, MA 02118

    htcohen@bu.edu

    Francis J. McGovern, M.D.

    Massachusetts General Hospital

    Boston, MA 02114

    References

    Atkins MB, Avigan DE, Bukowski RM, et al. Innovations and challenges in renal cancer: consensus statement from the first international conference. Clin Cancer Res 2004;10:6277S-6281S.

    Yang JC, Sherry RM, Steinberg SM, et al. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 2003;21:3127-3132.