Randomized Trial of Radiation Therapy With or Without Chemotherapy for Endometrial Cancer

RATIONALE: Drugs used in chemotherapy, such as cisplatin, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving chemotherapy together with radiation therapy is more effective than giving radiation therapy alone in treating endometrial cancer. PURPOSE: This randomized phase III trial is studying chemotherapy and radiation therapy to see how well they work compared with radiation therapy alone in treating patients with high-risk, stage I, stage II, or stage III endometrial cancer.

Sex

Female

Minimum age

18 Years

Maximum age

90 Years

Inclusion Criteria:

* Histologically confirmed endometrial carcinoma, with one of the following postoperative FIGO 2009 stages and grade:

  1. stage IA with invasion, grade 3 with documented LVSI
  2. stage IB grade 3
  3. stage II
  4. stage IIIA or IIIC; or IIIB if parametrial invasion only
  5. stage IA (with invasion), IB, II, or III with serous or clear cell histology
* WHO-performance status 0-2
* WBC ≥ 3.0 x 109/L.
* Platelets ≥ 100 x 109/L.
* Bilirubin ≤ 1.5 x UNL
* ASAT/ALAT ≤ 2.5 x UNL
* Written informed consent

Exclusion criteria:

* Uterine sarcoma (including carcinosarcoma)
* Previous malignancy (except for non-melanomatous skin cancer) \< 10 yrs
* Previous pelvic radiotherapy
* Hormonal therapy or chemotherapy for this tumor
* Macroscopic stage II for which Wertheim type hysterectomy (eligible if stage II grade 3 or stage III at pathology)
* Prior diagnosis of Crohn's disease or ulcerative colitis
* Residual macroscopic tumor after surgery
* Creatinine clearance ≤ 60 ml/min (Cockroft) or ≤ 50 ml/min (EDTA clearance, or measured creatinine clearance)
* Impaired cardiac function, prohibiting the infusion of large amounts of fluid during cisplatin therapy
* Peripheral Neuropathy \> or = grade 2
* Hearing impairment \> or = grade 3, or born deaf

• BACKGROUNDJameson MG, McNamara J, Bailey M, Metcalfe PE, Holloway LC, Foo K, Do V, Mileshkin L, Creutzberg CL, Khaw P. Results of the Australasian (Trans-Tasman Oncology Group) radiotherapy benchmarking exercise in preparation for participation in the PORTEC-3 trial. J Med Imaging Radiat Oncol. 2016 Aug;60(4):554-9. doi: 10.1111/1754-9485.12447. Epub 2016 Apr 5. PMID 27059658
• BACKGROUNDANZGOG and PORTEC Group; Blinman P, Mileshkin L, Khaw P, Goss G, Johnson C, Capp A, Brooks S, Wain G, Kolodziej I, Veillard AS, O'Connell R, Creutzberg CL, Stockler MR. Patients' and clinicians' preferences for adjuvant chemotherapy in endometrial cancer: an ANZGOG substudy of the PORTEC-3 intergroup randomised trial. Br J Cancer. 2016 Nov 8;115(10):1179-1185. doi: 10.1038/bjc.2016.323. Epub 2016 Oct 20. PMID 27764842
• RESULTde Boer SM, Wortman BG, Bosse T, Powell ME, Singh N, Hollema H, Wilson G, Chowdhury MN, Mileshkin L, Pyman J, Katsaros D, Carinelli S, Fyles A, McLachlin CM, Haie-Meder C, Duvillard P, Nout RA, Verhoeven-Adema KW, Putter H, Creutzberg CL, Smit VTHBM; for PORTEC Study Group. Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer. Ann Oncol. 2018 Feb 1;29(2):424-430. doi: 10.1093/annonc/mdx753. PMID 29190319
• RESULTde Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Kitchener HC, Nijman HW, Kruitwagen RF, Nout RA, Verhoeven-Adema KW, Smit VT, Putter H, Creutzberg CL; PORTEC study group. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1114-1126. doi: 10.1016/S1470-2045(16)30120-6. Epub 2016 Jul 7. PMID 27397040
• RESULTde Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jurgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Mar;19(3):295-309. doi: 10.1016/S1470-2045(18)30079-2. Epub 2018 Feb 12.