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Chemotherapy for Early-stage High-risk Endometrial Cancer
concomitant cisplatin (50mg/m
2
) on days one and 28 (RT–CT) followed designed or dimensioned to show non-inferiority, which actually
by four courses of paclitaxel (175mg/m
2
) and cisplatin (50mg/m
2
) at means that they are inconclusive.
21
Early results from an
four-week intervals. Patients with grade two or three endometrial NSGO/EORTC-trial comparing RT + CT with RT showed a significantly
adenocarcinoma with either >50% MI, cervical stromal invasion or improved PFS and a trend to better OS with the addition of CT.
19
Why,
pelvic-confined extrauterine disease were eligible. This treatment was then, could neither the Italian
17
nor the JGOG
18
study show any
feasible with excellent loco-regional control, suggesting additional difference between CT and RT? One reason might be that both used
effects of CT and radiation. Distant metastases continued to occur in CAP with fairly low dose intensities and low total doses. At the time
more advanced staged patients. these studies were planned, CAP was a common regimen in ovarian
cancer.
24
However, there is not much evidence that CAP is an active
Postoperative Radiation Therapy for regimen in EC.
8
However, both doxorubicin and cisplatin are included
Endometrial Carcinoma-3 in CAP and the majority of the patients in the NSGO/EORTC trial
The Postoperative Radiation Therapy for Endometrial Carcinoma were treated with AP with a fairly low dose intensity and a low total
(PORTEC) group has started an international randomised study dose. A notable difference between the NSGO/EORTC study and the
(PORTEC-3) with the RTOG concept.
23
They plan to randomise 800 Italian and JGOG trials is the sequential combination of RT and CT in
patients meeting one of the following criteria: FIGO stage IB grade 3 the NSGO/EORTC trial.
disease with documented lymph-vascular space invasion, stage IC–IIA
grade 3 disease, stage IIB, IIIA or IIIC any grade disease (stage IIIA It has almost taken half a century to show that adjuvant RT adds little
disease based on peritoneal cytology alone allowed if disease is grade to surgery as far as OS is concerned.
7
It now seems that CT + RT might
3) or stage IB–III disease with serous or clear-cell histology after TAH- be more effective than RT alone.
19,22
However, we do not know whether
BSO with no residual macroscopic tumour. They used TcP instead of adequate CT alone is as effective as CT + RT. We must not repeat the
the TP used in the RTOG pilot. The primary end-points are OS and mistake of adding together two toxic therapies without testing what RT
failure-free survival at five years. Secondary end-points are quality of adds to CT by carrying out the comparison of CT versus RT + CT. ■
life, severe treatment-related morbidity, rate of vaginal or pelvic
relapse and rate of distant metastases.
Thomas Hogberg is Head of the Department of Cancer
Epidemiology at the University of Lund and Director of
Discussion the Regional Tumour Registry of Southern Sweden at
There is one study showing superiority of CT over WART.
15
However,
Lund University Hospital. He is an Associate Professor of
Oncology at the University of Lund and was Head of the
this study is not a pure study of adjuvant therapy because it was
Department of Gynaecological Oncology at Lund
performed on a mixture of patients with no residual post-operative University Hospital from 1992 to 1997. He has been
tumour and patients with remaining residuals. The RT was WART,
Senior Consultant at the Departments of Gynaecological
Oncology at the Norwegian Radium Hospital and
which is not normally used in the adjuvant situation in early-stage EC.
Linköping University Hospital. Dr Hogberg is principal investigator of the NSGO-EC-
9501/EORTC 99551 study on sequential radiotherapy and chemotherapy in endometrial
Two fairly big randomised studies have failed to show differences in
cancer and a member of the Steering Committee of the Clinical Trial Unit within NSGO.
OS or PFS between CT and RT.
17,18
Neither of these trials was
1. Parkin DM, Bray F, Ferlay J, Pisani P, Global cancer 9. Aapro MS, van Wijk FH, Bolis G, et al., Doxorubicin versus Gynecologic Oncology Group Study, Gynecol Oncol, 1990;
statistics, 2002, CA Cancer J Clin, 2005;55:74–108. doxorubicin and cisplatin in EC: definitive results of a 36:166–71.
2. The National Board of Health and Welfare Centre for randomised study (55872) by the EORTC Gynaecological 17. Maggi R, Lissoni A, Spina F, et al., Adjuvant chemotherapy
Epidemiology. Cancer Incidence in Sweden 2007. Available Cancer Group, Ann Oncol, 2003;14:441–8. vs radiotherapy in high-risk EC: results of a randomised
at:
www.socialstyrelsen.se/Publicerat/2008/10204/2008- 10. Thigpen JT, Brady MF, Homesley HD, et al., Phase III trial of trial, Br J Cancer, 2006;95:266–71.
125-16.htm doxorubicin with or without cisplatin in advanced EC: a 18. Susumu N, Sagae S, Udagawa Y, et al., Randomized phase
3. Creasman WT, Odicino F, Maisonneuve P, et al., Carcinoma gynecologic oncology group study, J Clin Oncol, 2004;22: III trial of pelvic radiotherapy versus cisplatin-based
of the corpus uteri. FIGO 6th Annual Report on the Results 3902–8. combined chemotherapy in patients with intermediate-
of Treatment in Gynecological Cancer, Int J Gynaecol Obstet, 11. Fleming GF, Brunetto VL, Cella D, et al., Phase III trial of and high-risk EC: A Japanese Gynecologic Oncology Group
2006;95(Suppl. 1):S105–43. doxorubicin plus cisplatin with or without paclitaxel plus study, Gynecol Oncol, 2008;108:266–33.
4. Aalders JG, Abeler VM, Kolstad P, Onsrud M, Postoperative filgrastim in advanced EC: a Gynecologic Oncology Group 19. Hogberg T, Rosenberg P, Kristensen G, et al., A randomized
external irradiation and prognostic parameters in stage I Study, J Clin Oncol, 2004;22:2159–66. phase-III study on adjuvant treatment with radiation (RT) ±
endometrial carcinoma, Obstet Gynecol, 1980;56:419–26. 12. Sorbe B, Andersson H, Boman K, et al., Treatment of chemotherapy (CT) in early stage high-risk EC (NSGO-EC-
5. Creutzberg CL, van Putten WLJ, Koper PC, et al., Surgery primary advanced and recurrent EC with a combination of 9501/EORTC 55991), ASCO Annual Meeting Proceedings
and postoperative radiotherapy versus surgery alone for carboplatin and paclitaxel-long-term follow-up, Int J Gynecol Par I, J Clin Oncol, 2007;25(18S): abstract 5503.
patients with stage-1 endometrial carcinoma: multicentre Cancer, 2008;18:802–8. 20. Kuoppala T, Mäenpää J, Tomas E, et al., Surgically staged
randomised trial, Lancet, 2000;355:1404–11. 13. National Cancer Institute, GOG-209. Available at: high-risk endometrial cancer: randomized study of
6. Keys HM, Roberts JA, Brunetto VL, et al., A phase III trial of
www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=305 adjuvant radiotherapy alone vs. sequential chemo-
surgery with or without adjunctive external pelvic 940&protocolsearchid=4206096&version=healthprofessio radiotherapy, Gynecol Oncol, 2008;110:190–95.
radiation therapy in intermediate risk endometrial nal. 21. Altman DG, Bland JM, Absence of evidence is not
adenocarcinoma: a Gynecologic Oncology Group study, 14. Susumu N, Sagae S, Udagawa Y, Reply to Michael HR evidence of absence, BMJ, 1995;311:485.
Gynecol Oncol, 2004;92:744–51. Eichbaum et al. Adjuvant treatment of early-stage 22. Greven K, Winter K, Underhill K, et al., Final analysis of
7. The ASTEC/EN.5 writing committee on behalf of the endometrial cancer: Which patient can benefit from RTOG 9708: adjuvant postoperative irradiation combined
ASTEC/EN5 Study Group. Adjuvant external beam chemotherapy?, Gynecol Oncol, 2008;109:434–6. with cisplatin/paclitaxel chemotherapy following surgery
radiotherapy in the treatment of endometrial cancer (MRC 15. Randall ME, Filiaci VL, Muss H, et al., Randomized phase III for patients with high-risk EC, Gynecol Oncol, 2006;103:
ASTEC and NCIC CTG EN.5 randomised trials): pooled trial trial of whole-abdominal irradiation versus doxorubicin 155–9.
results, systematic review, and meta-analysis, Lancet, 2009; and cisplatin chemotherapy in advanced EC: a 23. National Cancer Institute. PORTEC 3. Available at: www.
373:137–47. Gynecologic Oncology Group Study, J Clin Oncol, 2006;24:
cancer.gov/search/ViewClinicalTrials.aspx?cdrid=521447&
8. Humber CE, Tierney JF, Symonds RP, et al., Chemotherapy 36–44. protocolsearchid=4206096&version=healthprofessional
for advanced, recurrent or metastatic EC: a systematic 16. Morrow CP, Bundy BN, Homesley HD, et al., Doxorubicin as 24. Hogberg T, Glimelius B, Nygren PA, Systematic overview of
review of Cochrane collaboration, Ann Oncol, 2007;18: an adjuvant following surgery and radiation therapy in chemotherapy effects in ovarian cancer, Acta Oncol, 2001;
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