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Journal of Clinical Oncology, Vol 23, No 6 (February 20), 2005: pp. 1323-1325 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.107
Prognostic Factors in Cytokine-Refractory Renal Cell Carcinoma Treated With Irinotecan, Cisplatin, and Mitomycin ChemotherapyDepartment of Medical Oncology, St Bartholomew's Hospital, London To the Editor: We read with interest the article by Motzer et al.1 They identified three prognostic factors for patients with previously treated renal cell carcinoma (RCC), which should allow stratification of patients before therapy into discrete risk groups. Since 1999, we have been using combination chemotherapy (irinotecan, cisplatin and mitomycin [IPM]) for the treatment of cytokine refractory RCC. To date, 62 patients have been treated. To receive therapy, patients had to have evidence of active disease progression before chemotherapy rather than just the persistence of disease after cytokine treatment. The results of therapy in the first 33 patients have already been published.2 Given that the therapy remained constant and the recruitment period was relatively short, we attempted to validate the prognostic factors suggested by Motzer et al, as well as test several additional factors in our population. The following factors were studied: low hemoglobin (Hb), increased calcium, increased lactate dehydrogenase, Eastern Cooperative Oncology Group performance status (PS; 0 or 1 v 2 or 3), absence of nephrectomy, and the presence of liver metastases. These were examined for progression-free survival (PFS) and overall survival (OS) after IPM chemotherapy (Table 1). For PFS, only Hb was significant (normal Hb, 8.9 months v low Hb, 3.8 months; P = .002). For OS, both low Hb and reduced PS were significant (normal Hb, 14.3 months v low Hb, 6.8 months; P = .001; and PS 0 or 1, 9.2 months v PS 2 or 3, 6.4 months; P = .02). Increased lactate dehydrogenase and serum calcium were not significant risk factors on univariate analysis.
For the risk factors identified by Motzer et al, 51 of the 62 patients had PS recorded. Of these, seven patients had favorable disease (zero risk factors), with a median PFS of 8.3 months and OS of 15.7 months; 26 patients had intermediate disease (one risk factor), with a median PFS of 3.0 months and OS of 8.0 months; and 18 had poor-risk disease (two risk factors), with a median PFS of 3.1 months and OS of 5.3 months (Fig. 1). Therefore, this validates Motzer's model in terms of prognostic significance.
It is noticeable that despite similar PFS in the two groups, the OS in our patients was much shorter, presumably because patients were being treated when they had active progression only. Because the risk factors identified by Motzer et al for post-cytokine survival also apply for untreated patients, it might be that chemotherapy is having no effect on patients who fail to respond to cytokines. Therefore, this was specifically investigated in our cohort. Fifty-two of our patients had cytokines for metastatic disease before IPM chemotherapy and were assessable for response to both. For those who had at least stable disease after treatment with cytokines (42%), their PFS after treatment with cytokines was 10.9 months. Sixty-four percent of these subsequently had at least stable disease after treatment with IPM, their PFS and OS was 7.5 and 11.2 months, respectively, versus 2.1 and 6.4 months (P < .001) for those who experienced disease progression while receiving IPM. For those who experienced disease progression while receiving cytokines (58%), their median PFS while receiving cytokines was 2.7 months. Fifty-six percent subsequently had at least stable disease with IPM, with PFS and OS of 6.2 and 11.6 months, respectively, versus 1.8 and 4.4 months for those who experienced disease progression while receiving IPM (P < .001). These results suggest that there is evidence of non–cross-resistance between cytokines and chemotherapy. We therefore concur with the results of Motzer et al in identifying Hb and PS as important risk factors for cytokine-refractory RCC. We also note a lack of cross-resistance between cytokines and the chemotherapy we have administered. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
REFERENCES
1. Motzer RJ, Bacik J, Schwarz LH, et al: Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 22:454-463, 2004 2. Shamash J, Steele JP, Wilson P, et al: IPM chemotherapy in cytokine refractory renal cell cancer. Br J Cancer 88:1516-1521, 2003[Medline]
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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