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Gynaecological Oncology
followed by one cycle of cisplatin) or whole abdominal radiotherapy occurred in either group. CT significantly improved PFS and OS in a
(WART) (30Gy in 20 fractions, with an additional 15Gy pelvic boost). subgroup of high- to intermediate-risk patients (stage IC patients over
Both OS and PFS were significantly better for patients in the CT arm. 70 years of age or having G3 endometrioid adenocarcinoma or stage
The treatment effect was comparable in subgroup analyses according II or IIIA [positive cytology]). However, the authors rightly pointed out
to stage, substage, age, cell type and residual disease status. Grade 3 that the validity of such a subgroup analysis is limited.
and four adverse effects (particularly haematological, gastrointestinal
[GI], cardiac and neurological) were significantly more common in the Nordic Society of Gynaecologic Oncology–
AP arm. Treatment may have contributed to the death of five patients Endometrial Cancer-9501/European Organisation for
in the WAR arm and eight patients in the AP arm. Research and Treatment of Cancer-55991
Early results of Nordic Society of Gynaecologoic Oncology–
Randomised Studies on Adjuvant Endometrial Cancer (NSGO-EC-9501/EORTC-55991) were presented at
Chemotherapy in Early Endometrial Cancer the American Society of Clinical Oncology (ASCO) in 2007.
19
Between
Gynecologic Oncology Group-34 1996 and 2007, 382 patients were randomised to adjuvant RT + CT or
The first randomised study (GOG-34) on the addition of adjuvant CT RT only. Patients with surgical stage I, II, IIIA (positive peritoneal fluid
(doxorubicin) after RT in EC was initiated in the late 1970s.
16
The study cytology only) or IIIC (positive pelvic lymph nodes only) were eligible if
has merely historical interest. It was terminated prematurely because they, according to departmental guidelines, had a sufficiently high risk
of slow recruitment, and the authors concluded that the study was of micrometastatic disease to qualify for adjuvant therapy. Patients
unable to determine what effect CT had on recurrence because of with serous, clear-cell or anaplastic carcinomas were eligible
protocol violations, small sample size and the number of patients lost regardless of other risk factors. Lymph-node exploration at staging
to follow-up. surgery was optional. All patients underwent at least total abdominal
hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO).
Italian Study
Between 1990 and 1997, an Italian study
17
randomised 345 (340 CT was given before or after pelvic RT (≥44Gy ± vaginal brachytherapy
evaluable) patients with endometrioid or adenosquamous carcinoma [VBT]). Before August 2004, CT consisted of four courses of cisplatin
and FIGO stage IC grade 3 or stage IIA–B grade 3 with ≥50% 50mg/m
2
and doxorubicin 50mg/m
2
or epirubicin 75mg/m
2
(AP) every
mechanical index myometrial invasion (MI) or FIGO stage III disease to four weeks. Thereafter, several CT regimens were allowed, of which AP
either adjuvant CT with cyclophosphamide 600mg/m
2
, doxorubicin (usually with cisplatin 75mg/m
2
), paclitaxel 175mg/m
2
, epirubicin
45mg/m
2
and cisplatin 50mgm
2
(CAP) administered every four weeks 60mg/m
2
and carboplatin area under curve (AUC) 5 (TEcP) and paclitaxel
for five cycles or pelvic RT at 45–50Gy. All patients underwent primary 175mg/m
2
+ carboplatin AUC 5–6 (TcP) were used (all alternatives
surgery. Pelvic and para-aortic node sampling was optional. The death usually every three weeks). The compliance to RT was very good – over
rate was 36% in the RT arm and 34% in the CT arm. The hazard ratios 90% of the patients in each arm completed RT, while compliance to CT
(HRs) for PFS and OS were 0.95 (confidence interval [CI] 0.66–1.36; was worse: 27% did not complete or did not receive CT. The median
p=0.78) and 0.88 (CI 0.63–1.23; p=0.45), respectively. Major late toxic follow-up time was 4.3 years. The HR for the primary end-point, PFS, was
effects in patients who received RT were mainly gastrointestinal (GI), 0.62 (CI 0.40–0.97; p=0.03), estimated five-year PFS was 72 and 79% and
including 3% with bowel obstruction, with three of five requiring for OS 0.65 (CI 0.40–1.06; p=0.08) and estimated five-year OS was 74 and
surgical intervention. The toxicity of CAP was mainly myelotoxicity. 82%, both in favour of RT + CT. The progression rate in the irradiated area
There were no treatment-related deaths. The distribution of local and in the RT group was 4% compared with 1% in the RT + CT group,
distant relapses in the respective randomisation arms suggests that suggesting a favourable interaction between RT and CT.
RT may achieve better loco-regional control while systemic CT may
better control distant metastases. The authors speculated if the Finnish Study
combination of concurrent or sequential adjuvant RT and CT could A randomised Finnish study also tried to combine CT and RT in an
further improve the results. unconventional way.
20
They gave split-course RT (2x28Gy separated by
a pause of three weeks) (n=72). In the CT + RT arm (n=84), one course
Japanese Gynecologic Oncology Group-2033 of cyclophosphamide 500mg/m
2
, epirubicin 60mg/m
2
and cisplatin
Between 1994 and 2000, 475 (385 eligible) patients with FIGO stage 50mg/m
2
(CEP) was given before RT, one in between the RT courses
IC–IIIC EC with ≥50% MI were randomised in JGOG-2033.
18
Patients and one after RT. Eligible patients had stage IA–B grade 3 or stage
were required to be under 75 years of age and to have undergone IC–IIIA grade 1–3. All patients underwent TAH-BSO and at least a
an initial surgery with no residual tumour. Pelvic lymphadenectomy pelvic lymphadenectomy was performed in 80% of the patients. The
was performed in 96% of the patients and para-aortic study was designed to detect a difference in OS of 20% with 60%
lymphadenectomy in 29%. Patients in the experimental arm received survival in the RT group. However, no significant survival difference
CAP – cyclophosphamide 333mg/m
2
, doxorubicin 40mg/m
2
and could be registered. The authors concluded that: “Age-adjusted
cisplatin 50mg/m
2
– every four weeks for three or more courses. sequential radio- and CT compared to radiotherapy alone did not alter
Patients in the control arm received pelvic RT at 45–50Gy. The five- the risk of death: HR 1.21 (95% CI 0.56–2.65)”. The study was not
year PFS was 84% in the RT group and 82% in the CT group (HR 1.07, powered to detect equality, and it is not appropriate to state that
CI 0.65–1.76; p=0.726), and five-year OS was 85% in the RT group and there is no difference – the result is consistent with the possibility that
87% in the CT group (HR 0.72, CI 0.40–1.29; p=0.268). The pattern of RT + CT was 44% better or 165% worse than RT alone.
21
progression did not differ between the groups. Grade 3–4 toxicities
were experienced in 2% of the RT and 5% of the CT group. Bowel Radiation Therapy Oncology Group-9708
obstructions were the main complications in the RT group, and The Radiation Therapy Oncology Group (RTOG) performed a pilot study
myelosuppression in the CT group. No treatment-related deaths (RTOG-9708)
22
combining adjuvant pelvic RT (45Gy + VBT) with
66 EUROPEAN OBSTETRICS & GYNAECOLOGY
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