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 Cooperative Group and the Medical Research Council.
AuthorsDe Wit, Ronald
Roberts, J Trevor
Wilkinson, Peter M
De Mulder, Pieter H M
Mead, Graham M
Fosså, S D
De Prijck, Linda
AffiliationRotterdam Cancer Institute and University Hospital, Rotterdam, The Netherlands. firstname.lastname@example.org
MetadataShow full item record
AbstractPURPOSE: To test the equivalence of three versus four cycles of bleomycin, etoposide, and cisplatin (BEP) and of the 5-day schedule versus 3 days per cycle in good-prognosis germ cell cancer. PATIENTS AND METHODS: The study was designed as a 2 x 2 factorial trial. The aim was to rule out a 5% decrease in the 2-year progression-free survival (PFS) rate. The study included the assessment of patient quality of life. A cycle of BEP consisted of etoposide 500 mg/m(2), administered at either 100 mg/m(2) days 1 through 5 or 165 mg/m(2) days 1 through 3, cisplatin 100 mg/m(2), administered at either 20 mg/m(2) days 1 through 5 or 50 mg/m(2) days 1 and 2. Bleomycin 30 mg was administered on days 1, 8, and 15 during cycles 1 through 3. The randomization procedure allowed some investigators to participate only in the comparison of three versus four cycles. RESULTS: From March 1995 until April 1998, 812 patients were randomly assigned to receive three or four cycles: of these, 681 were also randomly assigned to the 5-day or the 3-day schedule. Histology, marker values, and disease extent are well balanced in the treatment arms of the two comparisons. The projected 2-year PFS is 90.4% on three cycles and 89.4% on four cycles. The difference in PFS between three and four cycles is -1.0% (80% confidence limit [CL], -3.8%, +1.8%). Equivalence for three versus four cycles is claimed because both the upper and lower bounds of the 80% CL are less than 5%. In the 5- versus 3-day comparison, the projected 2-year PFS is 88.8% and 89.7%, respectively (difference, -0.9%, (80% CL, -4.1%, +2.2%). Hence, equivalence is claimed in this comparison also. Frequencies of hematologic and nonhematologic toxicities were essentially similar. Quality of life was maintained better in patients receiving three cycles; no differences were detected between 3 and 5 days of treatment. CONCLUSION: We conclude that three cycles of BEP, with etoposide at 500 mg/m(2), is sufficient therapy in good-prognosis germ cell cancer and that the administration of the chemotherapy in 3 days has no detrimental effect on the effectiveness of the BEP regimen.
CitationEquivalence 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 Cooperative Group and the Medical Research Council. 2001, 19 (6):1629-40 J. Clin. Oncol.
JournalJournal of Clinical Oncology
- Comparison of two standard chemotherapy regimens for good-prognosis germ cell tumors: updated analysis of a randomized trial.
- Authors: Grimison PS, Stockler MR, Thomson DB, Olver IN, Harvey VJ, Gebski VJ, Lewis CR, Levi JA, Boyer MJ, Gurney H, Craft P, Boland AL, Simes RJ, Toner GC
- Issue date: 2010 Aug 18
- Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial.
- Authors: Fizazi K, Pagliaro L, Laplanche A, Fléchon A, Mardiak J, Geoffrois L, Kerbrat P, Chevreau C, Delva R, Rolland F, Theodore C, Roubaud G, Gravis G, Eymard JC, Malhaire JP, Linassier C, Habibian M, Martin AL, Journeau F, Reckova M, Logothetis C, Culine S
- Issue date: 2014 Dec
- Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial.
- Authors: Horwich A, Sleijfer DT, Fosså SD, Kaye SB, Oliver RT, Cullen MH, Mead GM, de Wit R, de Mulder PH, Dearnaley DP, Cook PA, Sylvester RJ, Stenning SP
- Issue date: 1997 May
- Accelerated BEP for metastatic germ cell tumours: a multicenter phase II trial by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP).
- Authors: Grimison PS, Stockler MR, Chatfield M, Thomson DB, Gebski V, Friedlander M, Boland AL, Houghton B, Gurney H, Rosenthal M, Singhal N, Kichenadasse G, Wong SS, Lewis CR, Vasey PA, Toner GC, Australian and New Zealand Urogenital and Prostate Cancer Trials Group.
- Issue date: 2014 Jan
- Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: intergroup study EORTC 30983.
- Authors: de Wit R, Skoneczna I, Daugaard G, De Santis M, Garin A, Aass N, Witjes AJ, Albers P, White JD, Germa-Lluch JR, Marreaud S, Collette L
- Issue date: 2012 Mar 10
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Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2.Ingham, S; Warwick, J; Buchan, I; Sahin, S; O'Hara, Catherine; Moran, Anthony; Howell, Anthony; Evans, D; Centre for Health Informatics, Institute of Population Health, The University of Manchester, Manchester, UK. (2013-06)Mutations in BRCA1/2 genes confer ovarian, alongside breast, cancer risk. We examined the risk of developing ovarian cancer in BRCA1/2-positive families and if this risk is extended to BRCA negative families.
Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family.Evans, D Gareth R; Shenton, Andrew; Woodward, Emma; Lalloo, Fiona; Howell, Anthony; Maher, Eamonn R; Academic Unit of Medical Genetics and Regional Genetics Service, St Mary's Hospital Manchester M13 0JH, UK. email@example.com (2008)BACKGROUND: The identification of a BRCA1 or BRCA2 mutation in familial breast cancer kindreds allows genetic testing of at risk relatives. However, considerable controversy exists regarding the cancer risks in women who test positive for the family mutation. METHODS: We reviewed 385 unrelated families (223 with BRCA1 and 162 with BRCA2 mutations) ascertained through two regional cancer genetics services. We estimated the penetrance for both breast and ovarian cancer in female mutation carriers (904 proven mutation carriers - 1442 females in total assumed to carry the mutation) and also assessed the effect on penetrance of mutation position and birth cohort. RESULTS: Breast cancer penetrance to 70 and to 80 years was 68% (95%CI 64.7-71.3%) and 79.5% (95%CI 75.5-83.5%) respectively for BRCA1 and 75% (95%CI 71.7-78.3%) and 88% (95%CI 85.3-91.7%) for BRCA2. Ovarian cancer risk to 70 and to 80 years was 60% (95%CI 65-71%) and 65% (95%CI 75-84%) for BRCA1 and 30% (95%CI 25.5-34.5%) and 37% (95%CI 31.5-42.5%) for BRCA2. These risks were borne out by a prospective study of cancer in the families and genetic testing of unaffected relatives. We also found evidence of a strong cohort effect with women born after 1940 having a cumulative risk of 22% for breast cancer by 40 years of age compared to 8% in women born before 1930 (p = 0.0005). CONCLUSION: In high-risk families, selected in a genetics service setting, women who test positive for the familial BRCA1/BRCA2 mutation are likely to have cumulative breast cancer risks in keeping with the estimates obtained originally from large families. This is particularly true for women born after 1940.
Quality of life in good prognosis patients with metastatic germ cell cancer: a prospective study of the European Organization for Research and Treatment of Cancer Genitourinary Group/Medical Research Council Testicular Cancer Study Group (30941/TE20).Fosså, Sophie D; De Wit, Ronald; Roberts, J Trevor; Wilkinson, Peter M; De Mulder, Pieter H M; Mead, Graham M; Cook, Pat; De Prijck, Linda; Stenning, Sally P; Aaronson, N; Bottomley, Andrew; Collette, Laurence; Norwegian Radium Hospital, Oslo, Norway. firstname.lastname@example.org (2003-03-15)PURPOSE: To describe global quality of life (GLQL) in patients with metastatic testicular cancer (TC) treated with four different schedules of bleomycin, etoposide, and cisplatin (BEP) chemotherapy (four v three cycles given over 5 v 3 days). PATIENTS AND METHODS: Quality-of-life data were prospectively collected in 666 patients with metastatic TC entered into the European Organization for Research and Treatment of Cancer (EORTC) Trial 30941/United Kingdom Medical Research Council Trial TE20, using the EORTC Quality-of-Life Questionnaire C30 and a TC module. Data were analyzed by a mixed effects model and by evaluation of clinically relevant changes at 2 years. RESULTS: The pattern of GLQL changes was similar in the four groups. Two years after chemotherapy, 36% of patients displayed improved GLQL as compared with baseline, whereas GLQL had deteriorated in 13%. At 3 months, patients receiving the 3-day regimen experienced increased gastrointestinal (GI) toxicity more than those receiving the 5-day regimen, with the difference reaching the level of clinical relevance (>or = 10-point change) if four cycles were given. The 3-day schedule increased the 2-year risk of tinnitus, with clinical relevance demonstrated after four cycles. Long-term peripheral neuropathy and Raynaud-like phenomena were not associated with the number of cycles or days per cycle. At 2 years, Raynaud-like phenomena, tinnitus, or reduced hearing were reported by 21% to 26% of the patients. CONCLUSION: Because of the excess of acute GI toxicity and the increased risk of tinnitus after the 3-day regimen, we recommend the 5-day regimen if four cycles of BEP are planned. If only three cycles are to be given, then the 3-day regimen is acceptable, even given the increased risk of nausea/vomiting at 3 months.