|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 24, No 16 (June 1), 2006: pp. 2597-2598 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.05.6184
Bleomycin, Etoposide, and Cisplatin for Three Cycles Compared With Etoposide and Cisplatin for Four Cycles in Good-Risk Germ Cell Tumors: Is There a Preferred Regimen?Indiana University, Department of Medicine and Department of Urology, Indianapolis, IN To the Editor: We read with interest the original report "Etoposide and Cisplatin Chemotherapy for Metastatic Good-Risk Germ Cell Tumors" by Kondagunta et al.1 The Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY) group presented impressive results with etoposide and cisplatin (EP) for four cycles (x 4) in 289 patients treated from 1982 to 2002 with good-risk disease by International Germ Cell Cancer Collaborative Group (IGCCCG).2 They achieved 98% complete remissions with only 6% relapses. This is an update and expansion of their previously published data involving 214 patients treated from 1982 to 1990, but using a MSKCC definition of good risk.3 These results with EP x 4 appear competitive with results with bleomycin + EP (BEP) for three cycles (x 3) reported by numerous cooperative groups and single institutions.4-6 Results with BEP x 3 versus BEP x 4 for favorable disease, using the Indiana classification, were published in the Journal of Clinical Oncology in 1989.4 This included some patients who would have been classified as intermediate or poor risk by the IGCCCG. Nevertheless, 92% of patients were continuously disease free. Long-term follow-up for 118 patients treated at Indiana University (Indianapolis, IN) demonstrated that 102 of 104 patients with serum human chorionic gonadotropin levels less than 1,000 mU/mL were cured with BEP chemotherapy.5 Good-risk disease, as defined by the IGCCCG, comprises 60% of all germ cell tumors receiving chemotherapy for metastatic disease. This correspondence addresses two issues—the preferred regimen for good-risk disease and the role of postchemotherapy surgery. There are two commonly used regimens for good-risk disease, BEP x 3 and EP x 4. Reasons that one might prefer one regimen over the other are less toxicity or improved therapeutic efficacy. In our opinion, BEP x 3 has less toxicity due to shorter duration of cisplatin with less cumulative anorexia, nausea, ototoxicity, neurotoxicity, and sterility. The main reason to prefer EP x 4 over BEP x 3 relates to bleomycin pulmonary toxicity. Clinically significant pulmonary toxicity in good-risk patients receiving 9 weeks (270 U) of bleomycin is extremely rare.4-9 O'Sullivan et al10 retrospectively reviewed 835 patients treated at Royal Marsden Hospital (London, England) from 1982 to 1999 with platinum-bleomycin combination regimens. Fifty-seven patients (6.8%) had bleomycin pulmonary toxicity, ranging from simple x-ray changes (including computed tomography) to dyspnea. There were eight deaths (1%) attributed to bleomycin. Risk factors included greater than 300 units (10 weeks) of bleomycin, age older than 40 years, advanced disease, or poor renal function. The latter is not surprising since bleomycin is rapidly renal excreted. It is counterintuitive to use EP x 4 for good-risk disease for concern of pulmonary toxicity, yet routinely utilize BEP x 4 for advanced disease. We do not utilize a test dose of bleomycin at Indiana University at inception of BEP. We also do not routinely obtain pulmonary function tests with diffusion capacity in good-risk patients without adverse features.10 History and physical exam in our opinion is the most reliable parameters for follow-up. Respiratory lag and/or basilar inspiratory rates are signs to discontinue bleomycin. There is no evidence to suggest any therapeutic superiority of EP x 4 compared with BEP x 3. A European Organisation for the Research and Treatment of Cancer (EORTC) study compared four cycles of BEP with four cycles of EP.8 The complete response rate was 95% versus 87% favoring BEP (P = .0075). Ninety-three percent of BEP patients versus 90% EP patients are continuously with no evidence of disease. The MSKCC investigators11 point out that the differences favoring BEP might be due to the lower dose of etoposide (360 mg/M2) used in both arms. An alternate hypothesis is that BEP is slightly superior to EP. Culine et al12 randomly assigned 270 good-risk patients to BEP x 3 versus EP x 4, using the 500 mg/M2 etoposide dose in both arms. The event-free survival was superior favoring the BEP arm. One piece of evidence that is always incontrovertible is survival. There were 10 deaths on EP x 4 with versus five deaths with BEP with 92% versus 96% survival (P = .10). There were no deaths from bleomycin toxicity. There have been several other phase III studies published supporting the value of bleomycin.7,13 These studies all suggest either equivalence or superiority of bleomycin containing regimens, with negligible pulmonary toxicity. The beneficial role of postchemotherapy resection of radiographically residual masses has been well established for the past three decades. However, in most published studies of good-risk patients, only 25% to 40% underwent postchemotherapy resection.4,6,8 In the MSKCC article, 134 of 204 patients (66%) with nonseminomatous germ cell tumors had postchemotherapy resection.1 The findings of 51 cases of teratoma and 11 cases of viable cancer seem to justify this high incidence of postchemotherapy resection. According to their materials and methods section, "surgery was performed routinely for patients with residual disease on radiographs."1 Did they define this as nodal masses that were 1 cm or larger or simply normal sized, but visible nodes? I would imagine the latter with their unusually high incidence of postchemotherapy surgery. It is very probable, in our opinion, that many patients with microscopic postchemotherapy resection of mature teratoma will have biologically inert disease that does not grow nor lead to a late relapse. We have published two series involving 164 patients with late relapse seen at Indiana University. Most patients had initial chemotherapy elsewhere. The incidence is 2% to 3%. Most late relapses occur in patients with advanced disease at presentation or with postchemotherapy resection of bulky teratoma.14,15 In the Kondagunta article,1 they experienced three late relapses. In all of our series of good-risk patients, we have never performed postchemotherapy resection unless residual nodal disease was greater than 1 cm in maximal diameter. Arguably, we probably have left behind microscopic teratoma in some of these patients, but our risk of relapse (early or late) has remained around 5%, similar to the 6% in the Kondagunta article. In summary, we feel that BEP x 3 is the preferred regimen for good-risk disease. This decision is based on shorter duration of cisplatin with reduced cumulative anorexia, nausea, ototoxicity, neurotoxicity, and sterility, as well as the suggestion of improved survival with BEP x 3 versus EP x 4. This is in concordance with the recently published European consensus that states that "for patients with good prognosis disease, according to IGCCCG criteria, standard treatment is three cycles of BEP."16 We prefer EP x 4 for patients older than age 50, heavy smokers, or with serum creatinine higher than 2 mg/100 mL. However, the great majority of good-risk patients do not fall within any of these categories. We do not feel that patients who achieve a complete response (< 1 cm maximal diameter of lymph node) require postchemotherapy resection, whether patients present with good-risk, intermediate, or advanced disease. Our low relapse rate with long follow-up justifies this approach. This is also congruent with the European consensus.16 Authors' Disclosures of Potential Conflicts of Interest
Although all authors completed the disclosure declaration, the following author or immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.
Dollar Amount Codes (A) < $10,000 (B) $10,000-99,999 (C)
REFERENCES
1. Kondagunta GV, Bacik J, Bajorin DF, et al: Etoposide and cisplatin chemotherapy for metastatic good-risk germ cell tumors. J Clin Oncol 23:9290-9294, 2005 2. International Germ Cell Consensus Classification: A prognostic factor-based staging system for metastatic germ cell cancers –International Germ Cell Cancer Collaborative Group. J Clin Oncol 15:594-603, 1997 3. Xiao H, Mazumdar M, Bajorin DF, et al: Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin. J Clin Oncol 15:2553-2558, 1997 4. Einhorn LH, Williams SD, Loehrer PJ, et al: Evaluation of optimal duration of chemotherapy in favorable prognosis disseminated germ cell tumors: A Southeastern Cancer Study Group protocol. J Clin Oncol 7:387-391, 1989[Abstract] 5. Saxman SB, Finch D, Gonin R, et al: Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide and cisplatin in favorable prognosis germ cell tumors: The Indiana University experience. J Clin Oncol 16:702-706, 1998[Abstract] 6. deWit R, Roberts T, Wilkinson PM, et al: Equivalence of three or four cycles of bleomycin, etoposide and cisplatin chemotherapy and of a 3- or 5-day schedule in good prognosis germ cell cancer: A randomized study of the European Organization for Research and Treatment of Cancer Genitourinary tract cancer co-operative group and the Medical Research Council. J Clin Oncol 19:1629-1640, 2001 7. Loehrer PJ, Johnson D, Elson P, et al: Importance of bleomycin in favorable prognosis disseminated germ cell tumors: An Eastern Cooperative Oncology Group trial. J Clin Oncol 13:470-476, 1995 8. deWit R, Stoter G, Kaye SB, et al: Importance of bleomycin in combination chemotherapy for good prognostic testicular non-seminoma: A randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Co-operative Group. J Clin Oncol 15:1837-1843, 1997 9. Hinton S, Catalone PJ, Einhorn LH, et al: Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: Final analysis of an intergroup trial. Cancer 97:1869-1875, 2003[CrossRef][Medline] 10. O'Sullivan JM, Huddart RA, Norman AR, et al: Predicting the risk of bleomycin lung toxicity in patients with germ cell tumors. Ann Oncol 14:91-96, 2003 11. Bajorin DF, Bosl GJ: Bleomycin in germ cell tumor therapy: Not all regimens are created equal. J Clin Oncol 15:1717-1719, 1997 12. Culine S, Kerbrat P, Bouzy J, et al: The optimal chemotherapy regimen for good-risk metasatic non-seminomatous germ cell tumors (MNSGCT) is 3 cycles of bleomycin, etoposide, and cisplatin: Mature results of a randomized trial. Proc Am Soc Clin Oncol 21:382, 2003 (abstr 1536) 13. Levi JA, Raghavan D, Harvey V, et al: The importance of bleomycin in combination chemotherapy for good prognosis germ cell carcinoma. J Clin Oncol 11:1300-1305, 1993 14. Baniel J, Foster RS, Gonin R, et al: Late relapse of testicular cancer. J Clin Oncol 13:1170-1176, 1995[Abstract] 15. George DW, Foster RS, Hromas RA, et al: Update on late relapse of germ cell tumor: A clinical and molecular analysis. J Clin Oncol 21:113-122, 2003 16. Schmoll HJ, Souchon R, Krege S, et al: European consensus on diagnosis and treatment of germ cell cancer: A report of the European Germ Cell Cancer Consensus Group (EGCCCG). Ann Oncol 15:1377-1399, 2004
Related Reply
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
$100,000 (N/R) Not Required
