scholarly journals O010/#784 Adjuvant chemotherapy following chemo-radiation as primary treatment for locally advanced cervical cancer compared to chemo-radiation alone: the randomised phase 3 outback trial

2021 ◽  
Author(s):  
K Moore
Keyword(s):  
Cervical Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Primary Treatment ◽  
Advanced Cervical Cancer ◽  
Phase 3 ◽  
Locally Advanced Cervical Cancer

Adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: The randomized phase III OUTBACK Trial (ANZGOG 0902, RTOG 1174, NRG 0274).

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA3-LBA3
Author(s):  
Linda R. Mileshkin ◽  
Kathleen N. Moore ◽  
Elizabeth Barnes ◽  
Val Gebski ◽  
Kailash Narayan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Disease Recurrence ◽  
Primary Treatment ◽  
Phase Iii ◽  
Advanced Cervical Cancer ◽  
Treatment Groups ◽  
Locally Advanced Cervical Cancer

LBA3 Background: Cervical cancer is a common cause of cancer-related death among women worldwide. Standard treatment for locally advanced disease is chemoradiation. However, a significant percentage of women still relapse and die from the development of distant metastatic disease. OUTBACK was designed to determine the effects of giving adjuvant chemotherapy after chemoradiation on survival. Methods: OUTBACK is an international randomized phase III trial of the Gynecologic Cancer InterGroup (GCIG). Participating groups (countries) included ANZGOG (Australia and New Zealand), NRG (USA, Saudi Arabia, Canada, China), and Singapore. Eligible women had locally advanced cervical cancer (FIGO 2008 stage IB1 and node positive, IB2, II, IIIB or IVA) that was suitable for primary treatment with chemo-radiation with curative intent. Women were randomly assigned to either standard cisplatin-based chemo-radiation (control) or standard cisplatin-based chemo-radiation followed by adjuvant chemotherapy (ACT) with 4 cycles of carboplatin and paclitaxel, after stratification for nodal status, participating site, FIGO stage, age, and planned extended-field radiotherapy. The primary end point was overall survival (OS) at 5 years. Secondary endpoints included progression-free survival (PFS); adverse events (AE); and patterns of disease recurrence. The target sample size of 900 provided 80% power with 95% confidence to detect an improvement in OS at 5 years from 72% (control) to 80% (ACT), with some over-accrual to account for non-compliance with ACT and loss to follow-up. Results: 919 of 926 women recruited from April 2011 to June 2017 were eligible and included in the primary analysis: 463 assigned ACT, 456 control. ACT was started in 361 (78%) women assigned to receive it. Median follow-up was 60 months (IQR 45-65). OS at 5 years was similar in those assigned ACT versus control (72% vs 71%, difference <1%, 95% CI -6 to +7; P = 0.91). The hazard ratio for OS was 0·91, (95% CI 0.70 to 1.18). PFS at 5 years was similar in those assigned ACT versus control (63% vs 61%, difference 2%, 95% CI -5 to +9; P = 0.61). The hazard ratio for PFS was 0·87, (95% CI 0.70 to 1.08). AE of grade 3-5 within a year of randomisation occurred in 81% who were assigned and received ACT versus 62% assigned control. There was no evidence of differences between treatment groups in AE beyond 1 year of randomisation. Patterns of disease recurrence were similar in the two treatment groups. Conclusions: Adjuvant chemotherapy given after standard cisplatin-based chemoradiation for women with locally advanced cervical cancer did not improve OS or PFS. Clinical trial information: ACTRN12610000732088.

A phase III trial of adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: The OUTBACK TRIAL.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS5116-TPS5116
Author(s):  
Linda R. Mileshkin ◽  
Kailash Narayan ◽  
Kathleen N. Moore ◽  
Danny Rischin ◽  
Edward Lloyd Trimble ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
New Zealand ◽  
Adjuvant Chemotherapy ◽  
Gynecologic Cancer ◽  
Locally Advanced ◽  
Primary Objective ◽  
Phase Iii ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
The Usa

TPS5116 Background: Cervical cancer is a global health problem and the most common cause of cancer-related death among women in developing nations. Despite the recently developed cervical cancer vaccine, many women will continue to die from cervical cancer for many decades unless existing treatments can be improved. Unscreened women often present with locally-advanced disease that has a 5 year overall survival (OS) rate of 60% or less following standard chemo-radiation. Although some evidence suggests that adjuvant chemotherapy following chemo-radiation may be of value, its role remains controversial. Methods: OUTBACK is a randomized phase III Gynecologic Cancer InterGroup (GCIG) trial designed and led by the Australia New Zealand Gynaecological Oncology Group (ANZGOG) in collaboration with the NHMRC Clinical Trials Centre. Participating countries (groups) include Australia and New Zealand (ANZGOG), India, the USA and Canada (GOG, RTOG). OUTBACK is suitable for women with locally advanced cervical cancer (FIGO stage IB1 and node positive, IB2, II, IIIB or IVA). The primary objective is to determine if the addition of adjuvant chemotherapy to standard cisplatin-based chemo-radiation improves OS. Women are randomized to either A) standard cisplatin-based chemo-radiation or B) standard cisplatin-based chemo-radiation followed by 4 cycles of carboplatin and paclitaxel chemotherapy. Secondary objectives are to compare progression-free survival, treatment-related toxicity, patterns of disease recurrence, quality of life and psycho-sexual health, and the association between radiation protocol compliance and outcomes. Blood and tumour samples are collected from consenting patients for future translational studies. 780 women will be enrolled to determine if the addition of adjuvant chemotherapy can improve the 5-year OS rate by ≥ 10%. OUTBACK opened in Australia and New Zealand in 2011. In early 2012 the trial opened in the USA and activation of GOG sites is ongoing. 15 patients have been randomized. It is expected that RTOG and India will open the trial later this year with recruitment increasing substantially once all sites are activated.

scholarly journals Concurrent Definitive Chemoradiation Incorporating Intensity-Modulated Radiotherapy Followed by Adjuvant Chemotherapy in High Risk Locally Advanced Cervical Squamous Cancer: A Phase Ⅱ Study.

2021 ◽  
Author(s):  
Gong-yi ZHANG ◽  
ZHANG Rong ◽  
Ping BAI ◽  
Shu-min LI ◽  
Yuan-yuan ZHANG ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Intensity Modulated Radiotherapy ◽  
Advanced Cervical Cancer ◽  
Free Survival ◽  
Locally Advanced Cervical Cancer ◽  
Intensity Modulated ◽  
Grade 3

Abstract Background Although the prognosis of locally advanced cervical cancer has improved dramatically, survival for those with stage ⅢB-ⅣA disease or lymph nodes metastasis remains poor. It is believed that the incorporation of intensity-modulated radiotherapy into the treatment of cervical cancer might yield an improved loco-regional control, whereas more cycles of more potent chemotherapy after the completion of concurrent chemotherapy was associated with a diminished distant metastasis. We therefore initiated a non-randomized prospective phaseⅡ study to evaluate the feasibility of incorporating both these two treatment modality into the treatment of high risk locally advanced cervical cancer. Objectives to determine whether the incorporation of intensity-modulated radiotherapy and the addition of adjuvant paclitaxel plus cisplatin regimen into the treatment policy for patients with high risk locally advanced cervical cancer might improve their oncologic outcomes. Study Design: Patients were enrolled if they had biopsy proven stage ⅢA-ⅣA squamous cervical cancer or stage ⅡB disease with metastatic regional nodes. Intensity-modulated radiotherapy was delivered with dynamic multi-leaf collimators using 6MV photon beams. Prescription for PTV ranged from 45.0 ~ 50.0Gy at 1.8Gy ~ 2.0Gy/fraction in 25 fractions. Enlarged nodes were contoured separately and PTV-nodes were boosted simultaneously to a total dose of 50.0–65 Gy at 2.0- 2.6Gy/fraction in 25 fractions. A total dose of 28 ~ 35Gy high-dose- rate brachytherapy was prescribed to point A in 4 ~ 5 weekly fractions using an iridium- 192 source. Concurrent weekly intravenous cisplatin at 30mg/m2 was initiated on the first day of radiotherapy for over 1-hour during external-beam radiotherapy. Adjuvant chemotherapy was scheduled within 4 weeks after the completion of concurrent chemo-radiotherapy and repeated 3 weeks later. Paclitaxel 150 mg/m2 was given as a 3-hour infusion on day1, followed by cisplatin 35 mg/m2 with 1-hour infusion on day1-2 (70 mg/m2 in total). Results Fifty patients achieved complete response 4 weeks after the completion of the treatment protocol, whereas 2 patients had persistent disease. After a median follow-up period of 66 months, loco-regional (including 2 persistent disease), distant, and synchronous treatment failure occurred in 4 ,5, and 1, respectively. The 5-year disease-free survival, loco-regional recurrence-free survival, distant-metastasis recurrence-free survival was 80.5%, 90.3%, and 88.0%, respectively. Four of the patients died of the disease, and the 5-year overall survival was 92.1%. Most of the toxicities reported during concurrent chemo-radiotherapy were mild and transient. The occurrence of hematological toxicities elevated mildly during adjuvant chemotherapy, as 32% (16/50) and 4% (2/50) patients experienced grade 3–4 leukopenia and thrombocytopenia, respectively. Grade 3–4 late toxicities were reported in 3 patients. Conclusions The incorporation of intensity-modulated radiotherapy and adjuvant paclitaxel plus cisplatin chemotherapy were highly effective and well-tolerated in the treatment of high-risk locally advanced cervical cancer. The former yields an improved loco-regional control, whereas distant metastases could be effectively eradicated with mild toxicities when adjuvant regimen was prescribed.

scholarly journals Adjuvant Systemic Therapy after Chemoradiation and Brachytherapy for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1880
Author(s):  
Nanda Horeweg ◽  
Prachi Mittal ◽  
Patrycja L. Gradowska ◽  
Ingrid Boere ◽  
Supriya Chopra ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cervical Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Treatment Completion ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Hazard Ratios

Background: Standard of care for locally advanced cervical cancer is chemoradiation and brachytherapy. The addition of adjuvant systemic treatment may improve overall survival. A systematic review and meta-analysis was conducted to summarize evidence on survival outcomes, treatment completion and toxicity. Methods: PubMed, EMBASE and Web of Science were systematically searched for relevant prospective and retrospective studies. Two authors independently selected studies, extracted data and assessed study quality. Pooled hazard ratios for survival endpoints were estimated using random effect models. Weighted averages of treatment completion and toxicity rates were calculated and compared by the Fisher exact test. Results: The search returned 612 articles; 35 articles reporting on 29 different studies on adjuvant chemotherapy or immunotherapy were selected for systematic review. Twelve studies on an adjuvant platinum–pyrimidine antagonist or platinum–taxane were included for meta-analysis. The pooled hazard ratios for overall survival were 0.76 (99%CI: 0.43–1.34, p = 0.22) and 0.47 (99%CI: 0.12–1.86, p = 0.16) for the addition of, respectively, a platinum–pyrimidine antagonist or platinum–taxane to chemoradiation and brachytherapy. Completion rates were 82% (95%CI: 76–87%) for platinum–pyrimidine antagonist and 74% (95%CI: 63–85%) for platinum–taxane. Severe acute hematological and gastro-intestinal toxicities were significantly increased by adding adjuvant chemotherapy to chemoradiation and brachytherapy. Conclusions: The addition of adjuvant platinum–pyrimidine antagonist or platinum–taxane after chemoradiation and brachytherapy does not significantly improve overall survival, while acute toxicity is significantly increased. These adjuvant treatment strategies can therefore not be recommended for unselected patients with locally advanced cervical cancer.

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